1 00:00:05,800 --> 00:00:10,240 >>WELCOME TO THE INAUGURAL 2 00:00:10,240 --> 00:00:13,680 WALS LECTURE FOR THIS SEASON. 3 00:00:13,680 --> 00:00:16,440 I GATHER THIS IS THE 28TH 4 00:00:16,440 --> 00:00:18,880 SEASON. 5 00:00:18,880 --> 00:00:20,000 IT'S NOT EXACTLY THE NORMAL 6 00:00:20,000 --> 00:00:25,240 PLACE AND TIME, BUT THIS YEAR IT 7 00:00:25,240 --> 00:00:26,800 WILL BE IN THIS ROOM AND ONLINE 8 00:00:26,800 --> 00:00:28,400 AS IT USUALLY IS, SO WE HOPE TO 9 00:00:28,400 --> 00:00:30,600 SEE YOU ALL IN FUTURE WEEKS AS 10 00:00:30,600 --> 00:00:32,880 WELL. 11 00:00:32,880 --> 00:00:39,000 AND IT'S A REAL PLEASURE FOR 12 00:00:39,000 --> 00:00:42,080 LAMBDA LUNCH, A PROKARYOTIC 13 00:00:42,080 --> 00:00:43,720 INTEREST GROUP TO WELCOME JILL 14 00:00:43,720 --> 00:00:45,120 BANFIELD TO GIVE THIS FIRST 15 00:00:45,120 --> 00:00:45,640 LECTURE. 16 00:00:45,640 --> 00:00:50,920 THIS IS ALSO THE ROLLA DYER 17 00:00:50,920 --> 00:00:51,840 LECTURE, WHICH APPARENTLY HAS 18 00:00:51,840 --> 00:00:56,280 BEEN GOING ON SINCE 1950, WELL 19 00:00:56,280 --> 00:00:57,960 BEFORE WALS STARTED, AND THAT 20 00:00:57,960 --> 00:01:01,200 LECTURESHIP HONORS A FORMER NIH 21 00:01:01,200 --> 00:01:02,520 DIRECTOR, WHO WAS AN AUTHORITY 22 00:01:02,520 --> 00:01:03,840 ON INFECTIOUS DISEASE. 23 00:01:03,840 --> 00:01:06,240 SO EACH YEAR, THE DYER LECTURE 24 00:01:06,240 --> 00:01:08,120 IS PRESENTED BY AN 25 00:01:08,120 --> 00:01:09,680 INTERNATIONALLY RENOWNED 26 00:01:09,680 --> 00:01:11,800 RESEARCHER WHO HAS CONTRIBUTED 27 00:01:11,800 --> 00:01:13,680 SUBSTANTIALLY TO BIOLOGICAL 28 00:01:13,680 --> 00:01:15,640 KNOWLEDGE OF INFECTIOUS DISEASE 29 00:01:15,640 --> 00:01:18,040 AND IN THIS CASE MICROBES IN ALL 30 00:01:18,040 --> 00:01:19,160 PLACES WE FIND THEM. 31 00:01:19,160 --> 00:01:21,160 EACH YEAR, LAMBDA LUNCH, 32 00:01:21,160 --> 00:01:22,560 ALONG WITH OTHER INTEREST GROUPS 33 00:01:22,560 --> 00:01:26,680 AND PEOPLE ALL OVER NIH NOMINATE 34 00:01:26,680 --> 00:01:27,560 SPEAKERS. 35 00:01:27,560 --> 00:01:29,400 LAMBDA LUNCH SOLICITS 36 00:01:29,400 --> 00:01:30,640 NOMINATIONS FROM OUR MANY 37 00:01:30,640 --> 00:01:33,280 MEMBERS, AND WE VOTE AND JILL 38 00:01:33,280 --> 00:01:34,560 WAS AT THE TOP OF THE LIST, I 39 00:01:34,560 --> 00:01:36,080 THINK NOT JUST THIS YEAR, BUT 40 00:01:36,080 --> 00:01:37,600 THIS YEAR WE GOT -- OR LAST 41 00:01:37,600 --> 00:01:39,320 YEAR, WHEN THE INVITATIONS WENT 42 00:01:39,320 --> 00:01:39,880 OUT. 43 00:01:39,880 --> 00:01:41,560 SO WE'RE REALLY DELIGHTED THAT 44 00:01:41,560 --> 00:01:46,880 SHE COULD COME AND GIVE THIS 45 00:01:46,880 --> 00:01:47,320 TALK. 46 00:01:47,320 --> 00:01:50,080 SHE STARTED HER EDUCATION IN 47 00:01:50,080 --> 00:01:52,920 AUSTRALIA, WHERE SHE COMES FROM, 48 00:01:52,920 --> 00:01:55,400 CAME TO MARYLAND, TO HOPKINS FOR 49 00:01:55,400 --> 00:01:57,480 HER PH.D. IN EARTH AND PLANETARY 50 00:01:57,480 --> 00:02:01,920 SCIENCES, MOVED TO THE 51 00:02:01,920 --> 00:02:02,600 UNIVERSITY OF WISCONSIN AND WAS 52 00:02:02,600 --> 00:02:04,240 ON FACULTY THERE UNTIL 2001, 53 00:02:04,240 --> 00:02:07,480 WHEN SHE MOVED TO UC BERKELEY. 54 00:02:07,480 --> 00:02:09,280 THIS IS HER FIRST TRIP TO NIH. 55 00:02:09,280 --> 00:02:13,720 SO WE THOUGHT IT WAS MUCH 56 00:02:13,720 --> 00:02:14,560 OVERDUE. 57 00:02:14,560 --> 00:02:16,240 MAYBE THAT'S NOT SO SURPRISING, 58 00:02:16,240 --> 00:02:19,560 GIVEN SORT OF THE FIELD SHE 59 00:02:19,560 --> 00:02:21,160 COMES FROM HISTORICALLY, AND I 60 00:02:21,160 --> 00:02:22,480 THINK ALL OF US UNDERSTAND THAT 61 00:02:22,480 --> 00:02:24,960 SOME OF THE BEST SCIENCE COMES 62 00:02:24,960 --> 00:02:27,240 OUT OF PEOPLE FROM ONE FIELD 63 00:02:27,240 --> 00:02:30,680 MOVING INTO OTHERS OR LENDING 64 00:02:30,680 --> 00:02:31,720 THEIR EXPERTISE AND THEIR 65 00:02:31,720 --> 00:02:32,760 DIFFERENT WAYS OF LOOKING AT 66 00:02:32,760 --> 00:02:33,800 PROBLEMS TO ANOTHER FIELD. 67 00:02:33,800 --> 00:02:36,120 SO SHE COMES TO US FROM EARTH 68 00:02:36,120 --> 00:02:37,640 AND PLANETARY SCIENCES, WHERE 69 00:02:37,640 --> 00:02:41,240 SHE GOT HER PH.D., AND THE 70 00:02:41,240 --> 00:02:42,720 DEPARTMENT SHE'S IN NOW IN 71 00:02:42,720 --> 00:02:44,320 BERKELEY ARE MATERIALS SCIENCES 72 00:02:44,320 --> 00:02:45,880 AND ENGINEERING EARTH AND 73 00:02:45,880 --> 00:02:49,040 PLANETARY SCIENCES, 74 00:02:49,040 --> 00:02:50,280 ENVIRONMENTAL SCIENCE POLICY AND 75 00:02:50,280 --> 00:02:50,680 MANAGEMENT. 76 00:02:50,680 --> 00:02:53,400 SO NOT WHAT WE USUALLY GET TO 77 00:02:53,400 --> 00:02:56,560 HEAR, BUT THAT'S BETTER YET. 78 00:02:56,560 --> 00:03:00,000 HER WORK HAS REALLY -- ON 79 00:03:00,000 --> 00:03:01,040 NATURAL MICROBIAL COMMUNITIES 80 00:03:01,040 --> 00:03:08,080 HAS REALLY SPANNED FROM 81 00:03:08,080 --> 00:03:09,160 EX-TREATMENT ENVIRONMENTS TO THE 82 00:03:09,160 --> 00:03:10,640 INFANT GUT, SHE'S DONE A LOT OF 83 00:03:10,640 --> 00:03:12,000 WORK ON THE TREE OF LIFE. 84 00:03:12,000 --> 00:03:13,240 SHE'S RECOGNIZED WITH A LONG 85 00:03:13,240 --> 00:03:17,320 LIST OF HONORS, SOME OF THEM IN 86 00:03:17,320 --> 00:03:18,880 GEOCHEMISTRY, SOME IN 87 00:03:18,880 --> 00:03:19,600 MICROBIOLOGY, SOME IN JUST 88 00:03:19,600 --> 00:03:23,320 EVERYTHING. 89 00:03:23,320 --> 00:03:25,520 INCLUDING ELECTION TO THE 90 00:03:25,520 --> 00:03:27,960 NATIONAL ACADEMY OF SCIENCES. 91 00:03:27,960 --> 00:03:29,960 FOR THOSE OF YOU WHO WANT TO 92 00:03:29,960 --> 00:03:32,480 HEAR MORE AFTER TODAY'S LECTURE, 93 00:03:32,480 --> 00:03:35,320 THERE IS A LAMBDA LUNCH TOMORROW 94 00:03:35,320 --> 00:03:36,280 IN BUILDING 37. 95 00:03:36,280 --> 00:03:38,080 IT WILL ALSO BE ONLINE. 96 00:03:38,080 --> 00:03:39,760 IF YOU DON'T KNOW, THAT'S AT 97 00:03:39,760 --> 00:03:40,200 11:00. 98 00:03:40,200 --> 00:03:41,720 IF YOU DON'T KNOW WHERE AND WHEN 99 00:03:41,720 --> 00:03:44,200 THAT IS OR NEED THE LINK, EMAIL 100 00:03:44,200 --> 00:03:45,640 ME, SUSAN GOTTESMAN, AND I'LL 101 00:03:45,640 --> 00:03:49,680 SEND TO YOU. 102 00:03:49,680 --> 00:03:52,680 AND TODAY'S LECTURE IS OBLIGATE 103 00:03:52,680 --> 00:03:53,760 SYMBIONTS AND OTHER INTRIGUING 104 00:03:53,760 --> 00:03:56,280 MEMBERS OF HUMAN MICROBIOMES. 105 00:03:56,280 --> 00:03:58,680 I'M DELIGHTED TO WELCOME JILL TO 106 00:03:58,680 --> 00:04:04,960 NIH. 107 00:04:04,960 --> 00:04:05,880 [APPLAUSE] 108 00:04:05,880 --> 00:04:06,600 >> OKAY. 109 00:04:06,600 --> 00:04:07,200 GOOD AFTERNOON. 110 00:04:07,200 --> 00:04:08,800 CAN YOU HEAR ME? 111 00:04:08,800 --> 00:04:11,400 THANK YOU, SUSAN, FOR INVITING 112 00:04:11,400 --> 00:04:13,200 ME AND OTHERS WHO ARE INVOLVED 113 00:04:13,200 --> 00:04:15,200 IN THE INVITATION, AND CHRIS FOR 114 00:04:15,200 --> 00:04:16,600 MANAGING ALL OF THE 115 00:04:16,600 --> 00:04:17,360 ARRANGEMENTS. 116 00:04:17,360 --> 00:04:19,920 I REALLY WONDERED ABOUT THE 117 00:04:19,920 --> 00:04:21,160 WISDOM OF ALL THIS TRAVEL AT 118 00:04:21,160 --> 00:04:22,560 THIS TIME THAT I HADN'T BEEN TO 119 00:04:22,560 --> 00:04:24,240 NIH BEFORE AND I'M LIKE, I'VE 120 00:04:24,240 --> 00:04:26,600 JUST GOT TO GO. 121 00:04:26,600 --> 00:04:27,920 SO IT'S BEEN GREAT TO BE HERE SO 122 00:04:27,920 --> 00:04:29,320 FAR, I'VE MET ALL SORTS OF 123 00:04:29,320 --> 00:04:30,800 INTERESTING PEOPLE AND I HOPE 124 00:04:30,800 --> 00:04:32,520 I'LL GET TO MEET MORE OF YOU IN 125 00:04:32,520 --> 00:04:33,160 THE NEXT DAY. 126 00:04:33,160 --> 00:04:35,720 AS SUSAN MENTIONED, I'M AN EARTH 127 00:04:35,720 --> 00:04:36,680 SCIENTIST. 128 00:04:36,680 --> 00:04:38,240 I'M REALLY INTERESTED IN THE 129 00:04:38,240 --> 00:04:39,680 ENVIRONMENT AND ENVIRONMENTAL 130 00:04:39,680 --> 00:04:43,480 CHALLENGES OF CLIMATE CHANGE, 131 00:04:43,480 --> 00:04:44,800 AND MICROBIAL ROLES IN THOSE, 132 00:04:44,800 --> 00:04:48,520 BECAUSE AFTER ALL, THEY'RE RUN 133 00:04:48,520 --> 00:04:49,160 BY MICROBES. 134 00:04:49,160 --> 00:04:50,560 SO TODAY I'M GOING TO TALK TO 135 00:04:50,560 --> 00:04:52,840 YOU AT NIH ABOUT A TOPIC THAT 136 00:04:52,840 --> 00:04:54,960 CROSSES BETWEEN EARTH SCIENCE 137 00:04:54,960 --> 00:04:59,200 AND THE HUMAN MICROBIOME. 138 00:04:59,200 --> 00:05:00,680 BUT I WANTED TO START OUT BY 139 00:05:00,680 --> 00:05:02,440 SAYING THAT THE CONNECTION 140 00:05:02,440 --> 00:05:04,320 BETWEEN MICROBIOLOGY AND EARTH 141 00:05:04,320 --> 00:05:06,000 PROCESSES HAS BEEN IN PLACE 142 00:05:06,000 --> 00:05:08,520 SINCE THE VERY BEGINNING OF LIFE 143 00:05:08,520 --> 00:05:09,480 ON EARTH. 144 00:05:09,480 --> 00:05:12,360 OBVIOUSLY EARTH PROCESSES SUCH 145 00:05:12,360 --> 00:05:13,640 AS METAL DEGASSING AND THE 146 00:05:13,640 --> 00:05:16,920 APPEARANCE OF OCEANS, CHEMICAL 147 00:05:16,920 --> 00:05:17,800 WEATHERING, CHANGE THROUGH ITS 148 00:05:17,800 --> 00:05:18,520 ENVIRONMENTS AND PROVIDE 149 00:05:18,520 --> 00:05:21,400 OPPORTUNITY FOR BIOLOGY BUT THEN 150 00:05:21,400 --> 00:05:22,560 BIOLOGICAL INNOVATION FED BACK 151 00:05:22,560 --> 00:05:23,800 WITH CHANGES IN THE ENVIRONMENT, 152 00:05:23,800 --> 00:05:25,680 AND SO THOSE THINGS CYCLED OVER 153 00:05:25,680 --> 00:05:29,720 AND OVER AND OVER AGAIN, OVER 154 00:05:29,720 --> 00:05:30,760 AND OVER, OVER TIME. 155 00:05:30,760 --> 00:05:33,360 THE BIGGEST INNOVATION WE ALL 156 00:05:33,360 --> 00:05:35,040 RECOGNIZE IS THE APPEARANCE OF 157 00:05:35,040 --> 00:05:41,920 OXGENIC PHOTO SINT CYST 158 00:05:41,920 --> 00:05:43,520 OXGENIC PHOTOSYNTHESIS. 159 00:05:43,520 --> 00:05:45,560 WE HAVE THE APPEARANCE OF 160 00:05:45,560 --> 00:05:46,800 EUKARYOTES, DIVERSIFICATION OF 161 00:05:46,800 --> 00:05:49,600 YOU'RE KAY YOTS WITH PUNCTUATED 162 00:05:49,600 --> 00:05:50,920 CHANGES REMINDING US ACTUALLY 163 00:05:50,920 --> 00:05:52,720 THAT ALL OF GEOLOGY, ALL THE 164 00:05:52,720 --> 00:05:55,200 GEOSCIENCES WAS FOUNDED ON 165 00:05:55,200 --> 00:06:03,560 BIOLOGY BY THE PAIL RECORD. 166 00:06:03,560 --> 00:06:04,640 ACTUALLY THIS SORT OF FRAMES THE 167 00:06:04,640 --> 00:06:06,320 TOPIC I'M GOING TO TALK ABOUT 168 00:06:06,320 --> 00:06:07,600 TODAY WHEN WE LOOK AT THIS 169 00:06:07,600 --> 00:06:11,000 CARTOON, WE CAN SEE THAT THERE'S 170 00:06:11,000 --> 00:06:15,480 THIS SYSTEMATIC CHANGE IN LIFE'S 171 00:06:15,480 --> 00:06:16,840 MICROSCOPIC DIVERSITY AND OF 172 00:06:16,840 --> 00:06:18,960 COURSE ALONG WITH THIS CAME 173 00:06:18,960 --> 00:06:20,880 CHANGES IN THE MICROBIAL 174 00:06:20,880 --> 00:06:22,840 CONSORTIA THAT INHABIT THOSE 175 00:06:22,840 --> 00:06:23,120 ORGANISMS. 176 00:06:23,120 --> 00:06:24,400 SO AS WE LOOK TO THE MORE RECENT 177 00:06:24,400 --> 00:06:26,000 TIME PERIOD, WE MIGHT ASK WHERE 178 00:06:26,000 --> 00:06:32,640 DID THE ORGANISMS COME FROM THAT 179 00:06:32,640 --> 00:06:35,720 COLONIZED ANIMAL BO BODIES? 180 00:06:35,720 --> 00:06:36,840 THE MOST TRACTABLE PART OF THAT 181 00:06:36,840 --> 00:06:38,880 QUESTION WOULD HAVE TO BE THIS 182 00:06:38,880 --> 00:06:40,320 LAST PART WHERE IT'S RECENTLY 183 00:06:40,320 --> 00:06:41,720 INVOLVED HUMANS. 184 00:06:41,720 --> 00:06:43,040 IN PARALLEL WITH THIS, I 185 00:06:43,040 --> 00:06:46,640 INCLUDED A PICTURE OF THIS TREE, 186 00:06:46,640 --> 00:06:48,160 I'LL TALK ABOUT IT AGAIN IN A 187 00:06:48,160 --> 00:06:51,040 MOMENT BUT AS I'M SURE YOU'LL 188 00:06:51,040 --> 00:06:51,960 REALIZE, THE ORIGIN OF LIFE 189 00:06:51,960 --> 00:06:53,160 WOULD BE SOMEWHERE IN HERE, ALL 190 00:06:53,160 --> 00:06:54,560 THE LIVING THINGS ARE AT THE 191 00:06:54,560 --> 00:06:55,560 TIPS OF THE BRANCHES. 192 00:06:55,560 --> 00:06:56,880 SO ALL THESE BRANCHES OF 193 00:06:56,880 --> 00:06:59,000 ORGANISMS THAT APPEARED ACROSS 194 00:06:59,000 --> 00:07:01,600 DOMAIN BACTERIA AND ARCHAEA, OF 195 00:07:01,600 --> 00:07:03,480 COURSE, COME FROM THE FULL 196 00:07:03,480 --> 00:07:05,040 DIVERSITY OF ENVIRONMENTS, 197 00:07:05,040 --> 00:07:07,040 INCLUDING ANIMAL AND HUMAN 198 00:07:07,040 --> 00:07:10,000 MICROBIOMES. 199 00:07:10,000 --> 00:07:11,520 SO THIS IS THE QUESTION THAT I'M 200 00:07:11,520 --> 00:07:13,600 CURRENTLY RATHER INTERESTED IN: 201 00:07:13,600 --> 00:07:15,720 WHERE DO THE ORGANISMS THAT 202 00:07:15,720 --> 00:07:18,720 COLONIZE THE HUMAN BODY COME 203 00:07:18,720 --> 00:07:19,920 FROM? 204 00:07:19,920 --> 00:07:21,200 DO THEY DIFFER SUBSTANTIALLY 205 00:07:21,200 --> 00:07:22,960 FROM THE ORGANISMS THAT EXIST 206 00:07:22,960 --> 00:07:23,760 FROM THE ENVIRONMENT AND 207 00:07:23,760 --> 00:07:25,480 ASSUMING SO, HOW DO THEY DIFFER? 208 00:07:25,480 --> 00:07:27,440 HOW OFTEN WOULD THEIR 209 00:07:27,440 --> 00:07:28,360 TRANSITIONS FROM THE ENVIRONMENT 210 00:07:28,360 --> 00:07:30,360 INTO THE HUMAN BODY, AND I THINK 211 00:07:30,360 --> 00:07:31,480 A CORRELATE THAT WILL BE THE 212 00:07:31,480 --> 00:07:32,920 OPPOSITE DIRECTION BUT WE'RE NOT 213 00:07:32,920 --> 00:07:34,360 WORKING ON THAT YET, AND THEN 214 00:07:34,360 --> 00:07:36,000 FINALLY, WHAT WAS INVOLVED IN 215 00:07:36,000 --> 00:07:37,120 HABITAT TRANSITION, WHAT 216 00:07:37,120 --> 00:07:38,240 PROCESSES OCCURRED, WHEN DID 217 00:07:38,240 --> 00:07:43,520 THEY OCCUR RELATIVE TO THE 218 00:07:43,520 --> 00:07:45,880 COLONIZATION EVENT. 219 00:07:45,880 --> 00:07:47,160 SO I'M WORKING ALMOST 220 00:07:47,160 --> 00:07:49,120 EXCLUSIVELY IN WAYS THAT ARE 221 00:07:49,120 --> 00:07:53,040 FOUNDED ON GENOMIC -- MANY OF 222 00:07:53,040 --> 00:07:54,320 YOU ARE FAMILIAR WITH THE BASIC 223 00:07:54,320 --> 00:07:55,520 IDEA, MAYBE NOT ALL BECAUSE I 224 00:07:55,520 --> 00:07:57,520 KNOW A LOT OF PEOPLE DO SORT OF 225 00:07:57,520 --> 00:07:58,840 THE LABORATORY CULTIVATION, 226 00:07:58,840 --> 00:08:01,120 ISOLATION, GENETICS, 227 00:08:01,120 --> 00:08:01,680 BIOCHEMISTRY. 228 00:08:01,680 --> 00:08:03,320 THIS IS A KIND OF PARALLEL 229 00:08:03,320 --> 00:08:04,600 APPROACH, IT'S SOMETHING THAT I 230 00:08:04,600 --> 00:08:07,600 BEGAN WORKING ON RIGHT AT MY 231 00:08:07,600 --> 00:08:09,560 VERY EARLY START IN MICROBIOLOGY 232 00:08:09,560 --> 00:08:14,200 AROUND THE YEAR 2000. 233 00:08:14,200 --> 00:08:15,720 WE EMBRACE THE IDEA OF 234 00:08:15,720 --> 00:08:17,440 COMPLEXITY AS EARTH SCIENTISTS, 235 00:08:17,440 --> 00:08:18,720 THAT'S FUNDAMENTAL TO US, WE 236 00:08:18,720 --> 00:08:20,080 KNOW WE HAVE TO DEAL WITH 237 00:08:20,080 --> 00:08:21,120 COMPLEXITY, WE JUST DO THE BEST 238 00:08:21,120 --> 00:08:24,520 WE CAN TO SORT IT OUT, SO BY 239 00:08:24,520 --> 00:08:25,200 CAPTURING THE COMPLEXITY, WE 240 00:08:25,200 --> 00:08:26,440 HAVE THE OPPORTUNITY TO 241 00:08:26,440 --> 00:08:27,600 UNDERSTAND A LOT OF THE 242 00:08:27,600 --> 00:08:28,960 INTERACTIONS AND ASSOCIATIONS 243 00:08:28,960 --> 00:08:30,960 THAT WE MISSED IN PURE CULTURE 244 00:08:30,960 --> 00:08:31,360 WORK. 245 00:08:31,360 --> 00:08:32,640 MOST IMPORTANT, WE CAN STUDY 246 00:08:32,640 --> 00:08:34,160 ORGANISMS THAT ARE NOT AVAILABLE 247 00:08:34,160 --> 00:08:35,920 IN PURE CULTURE. 248 00:08:35,920 --> 00:08:37,680 INCLUDING PHAGES AND VIRUSES. 249 00:08:37,680 --> 00:08:38,840 SO THE APPROACH JUST STARTS 250 00:08:38,840 --> 00:08:40,040 SIMPLY WITH COLLECTION OF A 251 00:08:40,040 --> 00:08:42,280 SAMPLE THAT REPRESENTS THE WHOLE 252 00:08:42,280 --> 00:08:43,040 MICROBIAL COMMUNITY. 253 00:08:43,040 --> 00:08:45,760 WE THEN EXTRACT THE DNA, WE 254 00:08:45,760 --> 00:08:46,840 FRAGMENT IT. 255 00:08:46,840 --> 00:08:49,720 MOST OF THE WORK WE'VE DONE HAS 256 00:08:49,720 --> 00:09:00,120 BEEN WITH SHORT READS, ASSEMBLED 257 00:09:00,120 --> 00:09:00,960 INTO CONTINUOUS GENOME FRAGMENT 258 00:09:00,960 --> 00:09:04,280 THAT ARE THEN BINNED BY SOME 259 00:09:04,280 --> 00:09:06,120 ALGORITHM OR SERIES OF 260 00:09:06,120 --> 00:09:06,480 ALGORITHMS. 261 00:09:06,480 --> 00:09:09,400 THE BINS ARE TAKEN TO REPRESENT 262 00:09:09,400 --> 00:09:10,800 PARTIAL GENOMES, DRAFT GENOMES. 263 00:09:10,800 --> 00:09:13,200 SOME OF THOSE DRAFT GENOMES WILL 264 00:09:13,200 --> 00:09:15,400 COME FROM NON-CHROMOSOMAL 265 00:09:15,400 --> 00:09:16,400 ELEMENTS, AND I'M GOING TO TALK 266 00:09:16,400 --> 00:09:17,520 A LITTLE BIT ABOUT THOSE TODAY 267 00:09:17,520 --> 00:09:19,120 AND MORE IN THE LAMBDA LUNCH 268 00:09:19,120 --> 00:09:19,400 TOMORROW. 269 00:09:19,400 --> 00:09:21,080 AND THEN THERE'S THE POSSIBILITY 270 00:09:21,080 --> 00:09:24,160 THAT WE CAN IMPROVE THOSE DRAFT 271 00:09:24,160 --> 00:09:26,120 GENOMES AND ULTIMATELY ACHIEVE 272 00:09:26,120 --> 00:09:26,560 GENOME COMPLETION. 273 00:09:26,560 --> 00:09:28,440 NOW THIS IS NOT VERY OFTEN 274 00:09:28,440 --> 00:09:29,400 PERFORMED AND I'LL TALK AGAIN 275 00:09:29,400 --> 00:09:32,040 ABOUT THIS TOMORROW IN A LITTLE 276 00:09:32,040 --> 00:09:33,040 BIT MORE DETAIL, BUT IT IS 277 00:09:33,040 --> 00:09:34,000 POSSIBLE AND IT'S ACTUALLY 278 00:09:34,000 --> 00:09:34,920 REALLY IMPORTANT FOR SOME OF THE 279 00:09:34,920 --> 00:09:35,960 WORK THAT I WILL TELL YOU. 280 00:09:35,960 --> 00:09:37,280 I'M NOT GOING TO TELL YOU WHAT 281 00:09:37,280 --> 00:09:38,160 WENT INTO IT. 282 00:09:38,160 --> 00:09:39,920 IT'S QUITE TEDIOUS AT THIS TIME. 283 00:09:39,920 --> 00:09:41,000 BUT IT'S SUPER IMPORTANT IF 284 00:09:41,000 --> 00:09:42,480 WE'RE TO HAVE RELIABLE 285 00:09:42,480 --> 00:09:44,520 SEQUENCES. 286 00:09:44,520 --> 00:09:45,400 SO OFTEN I GET THE KIND OF 287 00:09:45,400 --> 00:09:48,120 COMMENT THAT, WELL, WHAT CAN YOU 288 00:09:48,120 --> 00:09:50,040 REALLY LEARN FROM METAGENOMES, 289 00:09:50,040 --> 00:09:51,440 THEY'RE JUST NOTHING AND ALL YOU 290 00:09:51,440 --> 00:09:53,040 REALLY SHOULD BE WORKING WITH IS 291 00:09:53,040 --> 00:09:53,680 EXPERIMENTS. 292 00:09:53,680 --> 00:09:55,360 WELL, I TOTALLY DON'T BELIEVE 293 00:09:55,360 --> 00:09:55,560 THAT. 294 00:09:55,560 --> 00:09:57,200 AND I THINK NOW THE DATA ARE 295 00:09:57,200 --> 00:09:58,400 ACCUMULATING THAT WE CAN BEGIN 296 00:09:58,400 --> 00:09:59,880 TO HAVE CONFIDENCE IN SOME OF 297 00:09:59,880 --> 00:10:01,080 THE KINDS OF INFERENCES WE CAN 298 00:10:01,080 --> 00:10:03,720 MAKE FROM GENOME SEQUENCES FROM 299 00:10:03,720 --> 00:10:05,720 ENVIRONMENTAL SAMPLES. 300 00:10:05,720 --> 00:10:07,120 AND SO I AGAIN PRESENT THIS TREE 301 00:10:07,120 --> 00:10:10,960 OF LIFE THAT WE PUBLISHED IN 302 00:10:10,960 --> 00:10:12,760 2016, WHICH WAS INTENDED TO 303 00:10:12,760 --> 00:10:14,400 CAPTURE A SENSE OF THE DIVERSITY 304 00:10:14,400 --> 00:10:15,800 OF LIFE THAT HAD COME TO LIGHT 305 00:10:15,800 --> 00:10:17,560 THROUGH GENOMES THROUGH 306 00:10:17,560 --> 00:10:18,080 METAGENOMES. 307 00:10:18,080 --> 00:10:21,040 SO THIS IS BASED ON GENOMES, AND 308 00:10:21,040 --> 00:10:23,560 THE GENOMES AT THE TIME WERE 309 00:10:23,560 --> 00:10:26,040 COMING FROM ALL OF EARTH'S 310 00:10:26,040 --> 00:10:27,040 ENVIRONMENTS. 311 00:10:27,040 --> 00:10:28,360 ESPECIALLY TERRESTRIAL 312 00:10:28,360 --> 00:10:29,440 ENVIRONMENTS THERE HAD BEEN VERY 313 00:10:29,440 --> 00:10:30,880 LITTLE STUDIES TO DATE. 314 00:10:30,880 --> 00:10:34,400 WHAT WE REALIZED TRUE THROUGH 315 00:10:34,400 --> 00:10:35,480 CONSTRUCTION OF THIS TREE 316 00:10:35,480 --> 00:10:36,800 CAPTURING ALL THE DIVERSITY IS 317 00:10:36,800 --> 00:10:39,800 THAT THE MAJORITY OF LINEAGES IN 318 00:10:39,800 --> 00:10:42,760 BACTERIA AND ARCHAEA ARE NOT 319 00:10:42,760 --> 00:10:44,240 REPRESENTED BY GENOMES IN PURE 320 00:10:44,240 --> 00:10:45,640 CULTURE. 321 00:10:45,640 --> 00:10:49,680 THEY REPRESENT APPROXIMATELY 322 00:10:49,680 --> 00:10:51,520 PHYLA -- AND EACH RED DOT MEANS 323 00:10:51,520 --> 00:10:56,240 THAT LINK YAJ LINEAGE HAS D 324 00:10:56,240 --> 00:10:56,600 REPRESENTATIVE. 325 00:10:56,600 --> 00:10:58,280 SO THAT MEANS WE'RE LEAVING OUT 326 00:10:58,280 --> 00:11:00,200 IN CULTIVATION-BASED STUDIES A 327 00:11:00,200 --> 00:11:02,800 HUGE MAJORITY, ACTUALLY, OF 328 00:11:02,800 --> 00:11:04,600 LIFE'S DIVERSITY AND PRESUMABLY 329 00:11:04,600 --> 00:11:06,040 BIOCHEMISTRY AND GENETICS. 330 00:11:06,040 --> 00:11:07,160 ONE OF THE FEATURES THAT REALLY 331 00:11:07,160 --> 00:11:08,800 STANDS OUT ON THIS TREE AND THE 332 00:11:08,800 --> 00:11:10,880 TREE WE'VE MADE PREVIOUSLY IN 333 00:11:10,880 --> 00:11:14,640 2015 IS THIS COLLECTION OF 334 00:11:14,640 --> 00:11:15,880 ORGANISMS FROM LINEAGES THAT 335 00:11:15,880 --> 00:11:18,800 HAVE NO ICE ISOLATED 336 00:11:18,800 --> 00:11:19,400 REPRESENTATIVES. 337 00:11:19,400 --> 00:11:22,960 THIS IS A MONO -- PRETTY MUCH 338 00:11:22,960 --> 00:11:24,280 EVERYONE WHO MAKES THESE TREES 339 00:11:24,280 --> 00:11:25,720 FINDS THE SAME RESULT AND ALL OF 340 00:11:25,720 --> 00:11:27,880 THE ORGANISMS HAVE NO ISOLATED 341 00:11:27,880 --> 00:11:29,320 REPRESENTATIVE. 342 00:11:29,320 --> 00:11:31,440 THE GENOMES ARE ALL SMALL IF NOT 343 00:11:31,440 --> 00:11:34,200 VERY, VERY SMALL. 344 00:11:34,200 --> 00:11:35,600 A SYMPTOM THAT WE PREDICTED 345 00:11:35,600 --> 00:11:36,520 WOULD MEAN THAT THE CELLS WOULD 346 00:11:36,520 --> 00:11:37,080 BE TINY. 347 00:11:37,080 --> 00:11:38,280 SO HERE WE HAVE A PREDICTION 348 00:11:38,280 --> 00:11:41,960 FROM THE GENOMES, BY FILTRATION 349 00:11:41,960 --> 00:11:43,080 THROUGH 0.2-MICRON FILTER, WE 350 00:11:43,080 --> 00:11:45,360 SHOW WE COULD ENRICH THOSE 351 00:11:45,360 --> 00:11:45,840 ORGANISMS. 352 00:11:45,840 --> 00:11:49,960 NOW A LOT OF SURVEYS, INCLUDING 353 00:11:49,960 --> 00:11:51,840 THE SURVEY -- CAPTURED CELLS ON 354 00:11:51,840 --> 00:11:54,960 TO A .2 AND EVEN .4 FILTER, 355 00:11:54,960 --> 00:11:57,120 THESE GO THROUGH, SO REALLY 356 00:11:57,120 --> 00:11:59,320 LIFE'S MINIMUM SIZE. 357 00:11:59,320 --> 00:12:01,000 THIS IS SHOWN NOT ONLY BY 358 00:12:01,000 --> 00:12:03,520 FILTRATION BASED ENRICHMENT BY 359 00:12:03,520 --> 00:12:04,400 CRY YOE TM. 360 00:12:04,400 --> 00:12:06,080 WE ALSO CAN PREDICT FROM THE 361 00:12:06,080 --> 00:12:06,840 GENOMES THAT THE CELLS SHOULD 362 00:12:06,840 --> 00:12:09,560 HAVE AN S LAYER, A SURFACE PROAT 363 00:12:09,560 --> 00:12:11,520 NAISHES LAYER AND SOMETHING WE 364 00:12:11,520 --> 00:12:14,320 CAN DIRECTLY VISUALIZE. 365 00:12:14,320 --> 00:12:15,080 WITH CRYOTM. 366 00:12:15,080 --> 00:12:20,080 THIS IS JUST A SLICE. 367 00:12:20,080 --> 00:12:21,640 BASED ON THE GENETIC REPERTOIRES 368 00:12:21,640 --> 00:12:23,960 OF THESE ORGANISMS, WE PREDICTED 369 00:12:23,960 --> 00:12:25,200 THEY WOULD BE OBLIGATE 370 00:12:25,200 --> 00:12:25,800 SYMBIONTS, AND BECAUSE OF THE 371 00:12:25,800 --> 00:12:27,160 KINDS OF ENVIRONMENTS THEY CAME 372 00:12:27,160 --> 00:12:30,480 FROM IN PART, WE SUGGESTED THAT 373 00:12:30,480 --> 00:12:32,360 THEY WERE PROBABLY SYMBIONTS OF 374 00:12:32,360 --> 00:12:33,080 OTHER MICROBES. 375 00:12:33,080 --> 00:12:35,080 THIS IS REALLY IN CONTRAST TO 376 00:12:35,080 --> 00:12:39,200 MOST SYMBIONTS KNOWN -- WHICH 377 00:12:39,200 --> 00:12:41,520 WERE MICROBIAL SYMBIONTS OF 378 00:12:41,520 --> 00:12:42,120 EUKARYOTES. 379 00:12:42,120 --> 00:12:43,680 SO THIS IS ACTUALLY SOMETHING 380 00:12:43,680 --> 00:12:45,120 THAT WE KNOW A LOT MORE ABOUT 381 00:12:45,120 --> 00:12:46,680 NOW THROUGH CO-CULTIVATION 382 00:12:46,680 --> 00:12:50,600 STUDIES AND FOR -- FROM 383 00:12:50,600 --> 00:12:52,120 ADDITIONAL CRYOTM OF SELECT 384 00:12:52,120 --> 00:12:52,720 ENVIRONMENTAL SAMPLES. 385 00:12:52,720 --> 00:12:54,880 JUST TO GIVE YOU A SENSE OF 386 00:12:54,880 --> 00:12:56,600 THESE ASSOCIATIONS, IN THE TOP 387 00:12:56,600 --> 00:12:58,080 LEFT-HAND CORNER, I APOLOGIZE 388 00:12:58,080 --> 00:12:59,680 IT'S A BIT HARD TO SEE, WE HAVE 389 00:12:59,680 --> 00:13:00,640 KIND OF THE ROAD MAP FOR THIS 390 00:13:00,640 --> 00:13:01,560 SLIDE. 391 00:13:01,560 --> 00:13:03,800 NOW IGNORE THE MOST PROMINENT 392 00:13:03,800 --> 00:13:05,800 FEATURE, WHICH IS THE FILM -- 393 00:13:05,800 --> 00:13:08,520 THAT NET IS JUST THE SUPPORT. 394 00:13:08,520 --> 00:13:10,040 FOCUS ON THIS BIG GREY BLOB, 395 00:13:10,040 --> 00:13:12,360 WHICH IS A SINGLE MICROBIAL CELL 396 00:13:12,360 --> 00:13:15,560 OF NORMAL SIZE. 397 00:13:15,560 --> 00:13:19,120 IN B, WE'VE EXPANDED THE VIEW OF 398 00:13:19,120 --> 00:13:20,240 THIS AND WHAT WE CAN SEE IS 399 00:13:20,240 --> 00:13:21,680 ATTACHED TO THE SURFACE OF THIS 400 00:13:21,680 --> 00:13:24,320 HOST CELL, IS A CHAIN OF CELLS 401 00:13:24,320 --> 00:13:25,640 UNDERGOING CELL DIVISION. 402 00:13:25,640 --> 00:13:28,000 THE CELL SIZE IS AROUND .2, 403 00:13:28,000 --> 00:13:29,160 .3 MICRONS IN DIAMETER. 404 00:13:29,160 --> 00:13:33,360 SO REALLY, REALLY TINY CELLS. 405 00:13:33,360 --> 00:13:35,360 AGAIN, WE CAN SEE THROUGH THESE 406 00:13:35,360 --> 00:13:38,480 CRYO TM DATA, MANY PILLAE 407 00:13:38,480 --> 00:13:40,360 SURROUNDING THE CELL, AS WELL AS 408 00:13:40,360 --> 00:13:41,400 PENETRATING THROUGH THE CELL 409 00:13:41,400 --> 00:13:43,000 WALL OF THE HOST INDICATING A 410 00:13:43,000 --> 00:13:45,320 MECHANISM FOR COMMUNICATION. 411 00:13:45,320 --> 00:13:48,240 WHICH IS SOMETHING THAT ALSO CAN 412 00:13:48,240 --> 00:13:50,800 BE DEDUCED FROM THE GENOMES FROM 413 00:13:50,800 --> 00:13:54,160 META GENOMES. 414 00:13:54,160 --> 00:13:55,280 SO I'M GOING TO TALK TODAY ABOUT 415 00:13:55,280 --> 00:13:57,120 THE ORGANISMS THAT COLONIZE THE 416 00:13:57,120 --> 00:13:59,400 HUMAN BODY, BUT ALSO HAVE 417 00:13:59,400 --> 00:14:00,200 REPRESENTATIVES IN THE 418 00:14:00,200 --> 00:14:01,360 ENVIRONMENT, FOCUSING ON THOSE 419 00:14:01,360 --> 00:14:02,440 LINEAGES FOR WHICH WE DON'T HAVE 420 00:14:02,440 --> 00:14:04,640 A LOT OF DATA FROM ISOLATE-BASED 421 00:14:04,640 --> 00:14:05,960 STUDIES. 422 00:14:05,960 --> 00:14:09,520 AND IN THE CPR, I SHOULD SAY -- 423 00:14:09,520 --> 00:14:10,880 LET'S GO BACK HERE A SECOND, 424 00:14:10,880 --> 00:14:15,840 THIS IS THE SPR, THESE TINY 425 00:14:15,840 --> 00:14:16,760 EPISYMBIONTS. 426 00:14:16,760 --> 00:14:18,520 WE HAVE THREE LINEAGES THAT ARE 427 00:14:18,520 --> 00:14:21,400 ROUTINELY ENCOUNTERED IN THE 428 00:14:21,400 --> 00:14:23,440 HUMAN. 429 00:14:23,440 --> 00:14:30,560 SACCHARIBACTERIA, TM7, BACILLAP 430 00:14:30,560 --> 00:14:35,080 BACTERIA AND ABSCONDITABACTERIA. 431 00:14:35,080 --> 00:14:38,720 AS WE LOOK ACROSS EARTH'S 432 00:14:38,720 --> 00:14:40,440 ENVIRONMENTS, WE FIND THAT THESE 433 00:14:40,440 --> 00:14:42,880 ORGANISMS OCCUR AS RELATIVELY 434 00:14:42,880 --> 00:14:44,800 LOW ABUNDANCE, SORT OF IN THE 435 00:14:44,800 --> 00:14:48,120 1%, SOMETIMES TO THE 10% MAXIMUM 436 00:14:48,120 --> 00:14:49,400 LEVEL, BUT THIS IS ACTUALLY NOT 437 00:14:49,400 --> 00:14:50,560 TO SAY THAT THEY'RE RARE 438 00:14:50,560 --> 00:14:51,440 COMPARATIVELY SPEAKING BECAUSE 439 00:14:51,440 --> 00:14:52,840 IN MANY OF THESE COMPLEX 440 00:14:52,840 --> 00:14:54,200 ENVIRONMENTS, THE MOST ABUNDANT 441 00:14:54,200 --> 00:14:57,200 ORGANISM IS ONLY 1% OF THE 442 00:14:57,200 --> 00:14:57,720 SAMPLE. 443 00:14:57,720 --> 00:15:01,680 WE ALSO SEE THE BLUE DOTS FOR 444 00:15:01,680 --> 00:15:02,560 SACCHARIBACTERIA ARE MORE 445 00:15:02,560 --> 00:15:04,440 NUMEROUS THAN THE OTHER DOTS, 446 00:15:04,440 --> 00:15:05,680 INDICATING THESE ARE THE MOST 447 00:15:05,680 --> 00:15:07,960 COMMONLY ENCOUNTERED GROUP OF 448 00:15:07,960 --> 00:15:09,120 THESE BACTERIA. 449 00:15:09,120 --> 00:15:11,200 IF WE ZOOM IN ON THE 450 00:15:11,200 --> 00:15:12,320 ANIMAL-ASSOCIATED GROUPS, WE 451 00:15:12,320 --> 00:15:15,760 FIND THAT THEY ARE FOUND IN TWO 452 00:15:15,760 --> 00:15:16,280 MAIN ENVIRONMENTS. 453 00:15:16,280 --> 00:15:18,000 BOTH IN HUMANS AND IN OTHER 454 00:15:18,000 --> 00:15:18,960 ANIMALS. 455 00:15:18,960 --> 00:15:25,320 IN THE GUT AND IN THE ORAL 456 00:15:25,320 --> 00:15:25,640 CAVITY. 457 00:15:25,640 --> 00:15:26,760 OTHERS HAVE WORKED ON THIS AND I 458 00:15:26,760 --> 00:15:29,080 WANT TO ACKNOWLEDGE THE WORK OF 459 00:15:29,080 --> 00:15:31,040 THE FORSYTHE INSTITUTE WHICH HAS 460 00:15:31,040 --> 00:15:32,040 BEEN ABSOLUTELY GROUND BREAKING 461 00:15:32,040 --> 00:15:33,480 IN UNDERSTANDING THIS KIND OF 462 00:15:33,480 --> 00:15:34,880 SYMBIOSIS IN THE HUMAN BODY. 463 00:15:34,880 --> 00:15:37,800 SO THIS IS A PAPER FROM THE 464 00:15:37,800 --> 00:15:39,040 FORSYTHE INSTITUTE, WHICH REALLY 465 00:15:39,040 --> 00:15:40,960 IS ONE OF A SERIES OF PAPERS 466 00:15:40,960 --> 00:15:44,040 THAT DEFINITIVELY SHOWED THAT 467 00:15:44,040 --> 00:15:46,000 SACCHARIBACTERIA IN THE ORAL 468 00:15:46,000 --> 00:15:50,040 CAVITY ARE AT THE SYMBIONTS OF 469 00:15:50,040 --> 00:15:52,200 ACTINOBACTERIA, SO NOW WE HAVE A 470 00:15:52,200 --> 00:15:54,520 HOST MICROBE EPI SYMBIONT PAIR. 471 00:15:54,520 --> 00:15:57,280 AGAIN WE SHOW IMAGES IN THIS 472 00:15:57,280 --> 00:15:59,760 CASE THESE IMAGES FROM THE PAPER 473 00:15:59,760 --> 00:16:02,520 INDICATE THE SACCHARIBACTERIA AS 474 00:16:02,520 --> 00:16:03,840 RED TINY DOTS, COMPARED TO THE 475 00:16:03,840 --> 00:16:09,360 BIG, BIG, BIG ATINOBACTERIAL 476 00:16:09,360 --> 00:16:11,160 CELLS, AND THEN ON THE THIRD 477 00:16:11,160 --> 00:16:13,120 SLIDE, THIRD IMAGE, WE CAN SEE A 478 00:16:13,120 --> 00:16:14,760 SCANNING ELECTRON MICROSCOPE 479 00:16:14,760 --> 00:16:14,960 IMAGE. 480 00:16:14,960 --> 00:16:15,880 I DON'T KNOW WHY THIS IS A 481 00:16:15,880 --> 00:16:17,240 LITTLE DARK, BUT YOU CAN SEE 482 00:16:17,240 --> 00:16:18,280 HERE THESE GREAT BIG THINGS, 483 00:16:18,280 --> 00:16:22,320 THOSE ARE THE ACTINOBACTERIA AND 484 00:16:22,320 --> 00:16:24,960 THESE ARE THE EP PI SYMBIONTS 485 00:16:24,960 --> 00:16:27,560 THAT DECORATE THE CELLS. 486 00:16:27,560 --> 00:16:34,640 THIS IS A CRYOMT IMAGE IN 487 00:16:34,640 --> 00:16:35,440 COLLABORATION WITH THEM, AND IT 488 00:16:35,440 --> 00:16:36,880 GIVES YOU A SLIGHTLY MORE 489 00:16:36,880 --> 00:16:39,120 DETAILED VIEW CLOSER UP VIEW OF 490 00:16:39,120 --> 00:16:39,920 THIS ASSOCIATION, YOU CAN SEE 491 00:16:39,920 --> 00:16:44,400 THE TIP OF THE ACTINOBACTERIA. 492 00:16:44,400 --> 00:16:49,920 AND THEN THE TINY LITTLE 493 00:16:49,920 --> 00:16:50,640 EPISIMBIOTIC CELL. 494 00:16:50,640 --> 00:16:51,840 I'M NOT GOING TO DWELL ON THIS, 495 00:16:51,840 --> 00:16:53,400 THIS IS NOT OUR WORK BUT I WANT 496 00:16:53,400 --> 00:16:55,600 TO ASSURE YOU AT NIH THESE 497 00:16:55,600 --> 00:16:56,680 PROBABLY DO HAVE MEDICAL 498 00:16:56,680 --> 00:16:57,120 SIGNIFICANCE. 499 00:16:57,120 --> 00:16:57,800 THERE ARE OTHERS WORKING ON 500 00:16:57,800 --> 00:16:58,000 THIS. 501 00:16:58,000 --> 00:17:01,720 THERE ARE INDICATIONS THAT 502 00:17:01,720 --> 00:17:03,240 SACCHARIBACTERIA HAVE AN IMPACT 503 00:17:03,240 --> 00:17:05,640 ON THE INCIDENCE OF 504 00:17:05,640 --> 00:17:07,240 PERIODONTITIS AND ARE INVOLVED 505 00:17:07,240 --> 00:17:11,960 IN REDUCING, AS I BELIEVE, BONE 506 00:17:11,960 --> 00:17:13,240 LOSS. 507 00:17:13,240 --> 00:17:14,280 DUE TO ASSOCIATED INFLAMMATION. 508 00:17:14,280 --> 00:17:15,280 SO THAT'S THE WORK OF OTHERS. 509 00:17:15,280 --> 00:17:17,520 I THINK IT JUST POINTS VERY 510 00:17:17,520 --> 00:17:18,640 CLEARLY TO THE NEED TO STUDY 511 00:17:18,640 --> 00:17:20,080 THESE ORGANISMS IN MORE DETAIL, 512 00:17:20,080 --> 00:17:25,400 AND THE NEED FOR INFORMATION 513 00:17:25,400 --> 00:17:26,960 ABOUT THE MECHANISMS BY WHICH 514 00:17:26,960 --> 00:17:28,320 THEY ASSOCIATE WITH THE HOSTS 515 00:17:28,320 --> 00:17:31,800 AND IMPACT THE HUMAN. 516 00:17:31,800 --> 00:17:33,080 BUT THE QUESTION I'M GOING TO 517 00:17:33,080 --> 00:17:34,520 TALK ABOUT FOR A LITTLE WHILE IS 518 00:17:34,520 --> 00:17:36,160 WHERE DO THEY COME FROM, HOW DO 519 00:17:36,160 --> 00:17:38,480 THEY GET THERE, WHAT COMES ALONG 520 00:17:38,480 --> 00:17:41,440 WITH THESE MIGRATIONS. 521 00:17:41,440 --> 00:17:42,920 SO WE HAVE DATA WHERE WE CAN 522 00:17:42,920 --> 00:17:44,480 FIND THESE ORGANISMS IN A 523 00:17:44,480 --> 00:17:45,520 VARIETY OF ENVIRONMENTS, WE'VE 524 00:17:45,520 --> 00:17:47,920 GOT GENOMES OF THE ORGANISMS IN 525 00:17:47,920 --> 00:17:49,480 THE MOUTH, FOR EXAMPLE, OR THE 526 00:17:49,480 --> 00:17:51,320 GUT. 527 00:17:51,320 --> 00:17:53,880 WE CAN ASK WHAT CHANGES IN GENE 528 00:17:53,880 --> 00:17:54,920 CONTENT WERE THEY, AND WHETHER 529 00:17:54,920 --> 00:17:56,680 DID THOSE CHANGES IN GENE 530 00:17:56,680 --> 00:17:57,840 CONTENT OCCUR AND HOW OFTEN HAVE 531 00:17:57,840 --> 00:17:59,560 THESE MIGRATIONS TAKEN PLACE? 532 00:17:59,560 --> 00:18:00,800 SO WE'RE JUST BEGINNING TO BUILD 533 00:18:00,800 --> 00:18:01,960 THIS PICTURE, BUT I THINK IT'S A 534 00:18:01,960 --> 00:18:04,480 VERY INTERESTING TOPIC AREA FOR 535 00:18:04,480 --> 00:18:06,360 UNDERSTANDING EVOLUTION OF 536 00:18:06,360 --> 00:18:08,880 MICROBES AND THE HUMAN 537 00:18:08,880 --> 00:18:09,200 MICROBIOME. 538 00:18:09,200 --> 00:18:11,800 SO THIS IS A PHYLOGENIC TREE ON 539 00:18:11,800 --> 00:18:13,360 THE LEFT FROM A PAPER BY ONE OF 540 00:18:13,360 --> 00:18:16,080 MY RECENTLY GRADUATED PH.D. 541 00:18:16,080 --> 00:18:17,160 STUDENTS, ALEX JAFFE. 542 00:18:17,160 --> 00:18:19,000 IT SHOWS THE THREE GROUPS THAT 543 00:18:19,000 --> 00:18:26,160 OCCUR IN THE HUMAN BODY 544 00:18:26,160 --> 00:18:27,360 ROUTINELY. 545 00:18:27,360 --> 00:18:31,160 THIS TREE IS CODED IN COLORS 546 00:18:31,160 --> 00:18:31,960 THAT INDICATE THE ENVIRONMENT 547 00:18:31,960 --> 00:18:34,320 FROM WHICH THESE ORGANISMS WERE 548 00:18:34,320 --> 00:18:35,680 DERIVED. 549 00:18:35,680 --> 00:18:39,360 THE TAKE-HOME PICTURE FROM THE 550 00:18:39,360 --> 00:18:42,560 THREE SEGMENTS OF THIS TREE WILL 551 00:18:42,560 --> 00:18:43,760 BE SHOWN IN THE NEXT SLIDE AND 552 00:18:43,760 --> 00:18:47,240 IN THE SLIDE ON THE RIGHT, WE 553 00:18:47,240 --> 00:18:51,080 CAN SEE IN BROWN COLOR THE 554 00:18:51,080 --> 00:18:52,280 LINEAGES OF ORGANISMS THAT ARE 555 00:18:52,280 --> 00:18:54,560 IN THE HUMAN BODY. 556 00:18:54,560 --> 00:18:55,760 AND WE CAN SEE THEY'RE RELATED 557 00:18:55,760 --> 00:19:02,600 TO EACH OTHER IN CLAIFS BUT IN 558 00:19:02,600 --> 00:19:05,160 THE CASE OF GRACILIBACTERIA, 559 00:19:05,160 --> 00:19:06,120 SUGGESTING THERE WERE SEVERAL 560 00:19:06,120 --> 00:19:08,760 MIGRATION EVENTS INTO THE HUMAN 561 00:19:08,760 --> 00:19:09,600 FROM NATURAL ENVIRONMENTS. 562 00:19:09,600 --> 00:19:14,120 IF WE LOOK AT THE FRANKING FLANG 563 00:19:14,120 --> 00:19:16,840 CODING, WE CAN SEE THESE WERE 564 00:19:16,840 --> 00:19:17,640 PROBABLY AQUEOUS FRESHWATER 565 00:19:17,640 --> 00:19:18,160 ENVIRONMENTS. 566 00:19:18,160 --> 00:19:22,040 THE DATA FOR ABSCONDITABACTERIA 567 00:19:22,040 --> 00:19:23,000 ARE VERY SLENDER. 568 00:19:23,000 --> 00:19:24,840 AT THE MOMENT THERE'S JUST ONE 569 00:19:24,840 --> 00:19:27,240 GROUP OF ABSCONDITABACTERIA 570 00:19:27,240 --> 00:19:28,760 FOUND IN THE HUMAN MOUTH. 571 00:19:28,760 --> 00:19:34,520 I NOTE HERE THESE TWO GROUPS USE 572 00:19:34,520 --> 00:19:36,360 AN ALTERNATE GENETIC CODE. 573 00:19:36,360 --> 00:19:37,440 I'M NOT GOING TO TALK ABOUT THAT 574 00:19:37,440 --> 00:19:38,560 IN THE CONTEXT OF THESE 575 00:19:38,560 --> 00:19:39,680 ORGANISMS BUT I WILL TALK ABOUT 576 00:19:39,680 --> 00:19:40,960 IT LATER IN THE CONTEXT OF 577 00:19:40,960 --> 00:19:41,920 PHAGES. 578 00:19:41,920 --> 00:19:43,200 OKAY. 579 00:19:43,200 --> 00:19:44,040 SACCHARIBACTERIA, MUCH BETTER 580 00:19:44,040 --> 00:19:44,600 SAMPLED. 581 00:19:44,600 --> 00:19:46,720 IN THIS CASE, WE CAN SEE SEVERAL 582 00:19:46,720 --> 00:19:49,840 LINEAGES OF ANIMAL-ASSOCIATED 583 00:19:49,840 --> 00:19:50,720 SACCHARIBACTERIA, AND AGAIN, 584 00:19:50,720 --> 00:19:53,840 GENERALLY SPEAKING, THE CLOSEST 585 00:19:53,840 --> 00:19:55,240 RELATION TO ORGANISMS ARE FROM 586 00:19:55,240 --> 00:19:56,520 THE AQUEOUS ENVIRONMENT. 587 00:19:56,520 --> 00:19:57,880 IT KIND OF MAKES SENSORILY, YOU 588 00:19:57,880 --> 00:19:58,840 CAN IMAGINE IF ORGANISMS ARE 589 00:19:58,840 --> 00:20:00,280 GOING TO GET INTO THE HUMAN 590 00:20:00,280 --> 00:20:01,480 BODY, THEY COULD VERY EASILY 591 00:20:01,480 --> 00:20:03,920 COME FROM FRESHWATER. 592 00:20:03,920 --> 00:20:08,320 WITH MULTI-PAL MULTIPLE CO. 593 00:20:08,320 --> 00:20:10,440 THE NEXT THING WE COULD ASK, HOW 594 00:20:10,440 --> 00:20:12,520 DO THESE ORGANISMS DIFFER? 595 00:20:12,520 --> 00:20:13,760 THE FIRST THING WE WANT TO LOOK 596 00:20:13,760 --> 00:20:14,920 AT IS GENOME SIZE. 597 00:20:14,920 --> 00:20:16,160 WHAT COMES TO LIGHT WHEN WE LOOK 598 00:20:16,160 --> 00:20:19,080 AT THE GENOME SIZES OF THESE 599 00:20:19,080 --> 00:20:20,440 THREE GROUPS IN -- ACTUALLY THIS 600 00:20:20,440 --> 00:20:23,440 ONE JUST SHOWS SACCHARIBACTERIA, 601 00:20:23,440 --> 00:20:24,240 ONE OF THE THREE GROUPS. 602 00:20:24,240 --> 00:20:25,960 IN THESE DIFFERENT HABITAT TYPES 603 00:20:25,960 --> 00:20:28,720 WITH GENOME SIZE ON THE X AXIS, 604 00:20:28,720 --> 00:20:30,880 THIS HERE IS PROTEOME SIZE, 605 00:20:30,880 --> 00:20:32,160 BASICALLY A PROXY FOR GENOME 606 00:20:32,160 --> 00:20:32,360 SIZE. 607 00:20:32,360 --> 00:20:33,840 WE HAVE ACCOUNTED FOR THE FACT 608 00:20:33,840 --> 00:20:35,960 THAT MANY OF THESE GENOMES ARE 609 00:20:35,960 --> 00:20:37,120 ONLY PARTIAL, EVEN ACCOUNTING 610 00:20:37,120 --> 00:20:39,040 FOR THAT, IT'S PRETTY CLEAR THAT 611 00:20:39,040 --> 00:20:40,520 THE ANIMAL-ASSOCIATED ORGANISMS 612 00:20:40,520 --> 00:20:41,680 HAVE SUBSTANTIALLY SMALLER 613 00:20:41,680 --> 00:20:44,560 GENOMES THAN THOSE THAT -- THEIR 614 00:20:44,560 --> 00:20:47,240 RELATIVES THAT OLE KUR IN THE 615 00:20:47,240 --> 00:20:47,880 ENVIRONMENT. 616 00:20:47,880 --> 00:20:48,760 SO THAT MIGHT MOTIVATE YOU TO 617 00:20:48,760 --> 00:20:51,520 ASK WHAT ABOUT THEIR METABOLIC 618 00:20:51,520 --> 00:20:52,400 CAPACITIES, HOW DO THEY DIFFER, 619 00:20:52,400 --> 00:20:53,920 WHAT IS THE PHYSIOLOGICAL CHANGE 620 00:20:53,920 --> 00:20:56,400 THAT TOOK PLACE ONCE THESE 621 00:20:56,400 --> 00:20:58,040 ORGANISMS BECAME ANIMAL OR 622 00:20:58,040 --> 00:20:59,840 HUMAN-ASSOCIATED? 623 00:20:59,840 --> 00:21:01,200 WELL, TO DO THIS, WE'RE GOING TO 624 00:21:01,200 --> 00:21:02,560 USE A PROTEIN FAMILY-BASED 625 00:21:02,560 --> 00:21:03,640 APPROACH, AND I'M GOING TO 626 00:21:03,640 --> 00:21:05,440 EXPLAIN TO YOU BEFORE I SHOW YOU 627 00:21:05,440 --> 00:21:06,880 THE DATA. 628 00:21:06,880 --> 00:21:08,480 YOU START WITH ALL THE PREDICTED 629 00:21:08,480 --> 00:21:10,120 PROTEINS FROM ALL THE GENOMES. 630 00:21:10,120 --> 00:21:11,560 AND THEN YOU GROUP THE PROTEINS 631 00:21:11,560 --> 00:21:20,760 TOGETHER BY BUILDING HIDDEN 632 00:21:20,760 --> 00:21:22,080 MARKOFF MODELS, SUCH THAT YOU 633 00:21:22,080 --> 00:21:23,400 CAN GROUP THINGS INTO FAMILIES 634 00:21:23,400 --> 00:21:24,840 WHERE THE FAMILY HAS A FUNCTION 635 00:21:24,840 --> 00:21:26,200 MORE OR LESS REPRESENTS ONE 636 00:21:26,200 --> 00:21:31,040 FUNCTION. 637 00:21:31,040 --> 00:21:31,760 SO ONE WHERE WE KNOW THE 638 00:21:31,760 --> 00:21:32,320 FUNCTION. 639 00:21:32,320 --> 00:21:33,240 IT DOESN'T MATTER IF YOU DON'T 640 00:21:33,240 --> 00:21:34,160 KNOW THE FUNCTION, YOU STILL 641 00:21:34,160 --> 00:21:34,920 HAVE THE SEQUENCE. 642 00:21:34,920 --> 00:21:36,440 SO YOU CAN INCLUDE EVERYTHING IN 643 00:21:36,440 --> 00:21:39,080 THE ANALYSIS. 644 00:21:39,080 --> 00:21:41,600 AND SO WE THEN GO GENOME BY 645 00:21:41,600 --> 00:21:43,240 GENOME AND WE ASK, DOES THIS 646 00:21:43,240 --> 00:21:44,320 PROTEIN FAMILY, AND WE'RE 647 00:21:44,320 --> 00:21:45,640 TALKING MAYBE 20,000 PROTEIN 648 00:21:45,640 --> 00:21:46,960 FAMILIES, DOES THIS PROTEIN 649 00:21:46,960 --> 00:21:48,360 FAMILY OCCUR IN THIS GENOME, YES 650 00:21:48,360 --> 00:21:49,280 OR NO? 651 00:21:49,280 --> 00:21:50,960 THIS PART IS GOING TO BE A 652 00:21:50,960 --> 00:21:52,200 YES-NO PLOT WHERE YES IS BLUE 653 00:21:52,200 --> 00:21:53,960 AND NO IS WHITE. 654 00:21:53,960 --> 00:21:58,400 AND SO THIS IS JUST A 2 BY 2, 2 655 00:21:58,400 --> 00:21:59,040 GENOMES, TWO PROTEIN FAMILY, YOU 656 00:21:59,040 --> 00:22:01,120 CAN SEE HERE WE'RE GOING TO CODE 657 00:22:01,120 --> 00:22:02,400 IT, TRUE AND FALSE. 658 00:22:02,400 --> 00:22:03,640 FOUR GENOMES, THREE FAMILIES, 659 00:22:03,640 --> 00:22:04,560 WE'RE GOING TO GET A SENSE OF 660 00:22:04,560 --> 00:22:07,160 WHERE THESE PROTEIN FAMILIES 661 00:22:07,160 --> 00:22:08,840 OCCUR ACROSS GENOMES AND THEN BY 662 00:22:08,840 --> 00:22:09,920 MAPPING ON THE ENVIRONMENT 663 00:22:09,920 --> 00:22:10,560 ACROSS THE ENVIRONMENT. 664 00:22:10,560 --> 00:22:13,240 SO WE CAN CORRELATE FUNCTION TO 665 00:22:13,240 --> 00:22:15,040 ENVIRONMENT IF POSSIBLE. 666 00:22:15,040 --> 00:22:18,240 SO THE NEXT SLIDE, WE'RE GOING 667 00:22:18,240 --> 00:22:19,640 TO ZOOM WAY OUT AND SEE 668 00:22:19,640 --> 00:22:20,920 THOUSANDS OF PROTEIN FAMILIES 669 00:22:20,920 --> 00:22:21,840 AND HUNDREDS OF GENOMES. 670 00:22:21,840 --> 00:22:23,280 BUT IT'S BASICALLY SET UP LIKE 671 00:22:23,280 --> 00:22:26,960 THIS. 672 00:22:26,960 --> 00:22:28,160 SO THIS IS WHAT IT LOOKS LIKE, 673 00:22:28,160 --> 00:22:30,160 AND THIS IS JUST FOR 674 00:22:30,160 --> 00:22:31,920 SACCHARIBACTERIA. 675 00:22:31,920 --> 00:22:34,320 THIS PARTICULAR SLIDE. 676 00:22:34,320 --> 00:22:37,480 AGAIN, COLUMNS OF PROTEIN 677 00:22:37,480 --> 00:22:38,840 FAMILIES, PRESENCE, BLUE, 678 00:22:38,840 --> 00:22:39,880 ABSENCE, WHITE. 679 00:22:39,880 --> 00:22:45,440 THE GENOMES ARE ARRANGED BASED 680 00:22:45,440 --> 00:22:47,200 ON THE PHYLOGENETIC TREE BASED 681 00:22:47,200 --> 00:22:49,280 ON THE ANALYSIS OF 682 00:22:49,280 --> 00:22:50,360 PHYLOGENETICALLY INFORMED GENES. 683 00:22:50,360 --> 00:22:52,040 SO RIGHT AWAY, YOU CAN SEE THAT 684 00:22:52,040 --> 00:22:53,240 THERE ARE SOME PROTEIN FAMILIES 685 00:22:53,240 --> 00:22:55,160 THAT ARE WIDELY DISTRIBUTED IF 686 00:22:55,160 --> 00:22:57,040 NOT UBIQUITOUS ACROSS THESE 687 00:22:57,040 --> 00:23:01,160 DRAFT AND PARTIAL LIQUEUR ATED 688 00:23:01,160 --> 00:23:02,400 AND COMPLETE GENOMES. 689 00:23:02,400 --> 00:23:04,040 THOSE OBVIOUSLY THE GENES 690 00:23:04,040 --> 00:23:05,920 INVOLVED IN CONSERVED FUNCTIONS, 691 00:23:05,920 --> 00:23:08,640 SUCH AS RIBOSOME CONSTRUCTION, 692 00:23:08,640 --> 00:23:11,840 TRANSLATION, TRANSCRIPTION. 693 00:23:11,840 --> 00:23:13,240 BUT WE ALSO SEE GROUPS OF 694 00:23:13,240 --> 00:23:17,080 PROTEIN FAMILIES THAT ARE 695 00:23:17,080 --> 00:23:21,240 REPRESENTED BY BLOCKS OF BLUE 696 00:23:21,240 --> 00:23:22,280 THAT ARE SPECIFIC TO CERTAIN 697 00:23:22,280 --> 00:23:25,720 ENVIRONMENTS. 698 00:23:25,720 --> 00:23:27,920 AND BY GOING IN AND LOOKING AT 699 00:23:27,920 --> 00:23:29,480 WHAT THE PROTEIN FAMILIES ARE IN 700 00:23:29,480 --> 00:23:30,760 THE INDIVIDUAL CASES AND THEN IN 701 00:23:30,760 --> 00:23:32,160 GROUPS OF PROTEIN FAMILIES, WE 702 00:23:32,160 --> 00:23:37,160 START TO GET A SENSE OF WHAT 703 00:23:37,160 --> 00:23:38,400 THESE PROTEINS DO IN THE CASE 704 00:23:38,400 --> 00:23:39,160 THAT THEY ARE 705 00:23:39,160 --> 00:23:39,840 ENVIRONMENT-SPECIFIC. 706 00:23:39,840 --> 00:23:40,800 THERE'S NOT A LOT OF INFORMATION 707 00:23:40,800 --> 00:23:42,520 IN THESE ORGANISMS BECAUSE WELL 708 00:23:42,520 --> 00:23:44,280 OVER HALF THE GENES HAVE NO 709 00:23:44,280 --> 00:23:44,960 PREDICTED FUNCTION, SO THERE'S A 710 00:23:44,960 --> 00:23:46,040 LOT OF PROTEIN FAMILIES THAT 711 00:23:46,040 --> 00:23:47,160 HAVE NO FUNCTIONAL PREDICTION, 712 00:23:47,160 --> 00:23:48,960 BUT WE CAN START TO IDENTIFY 713 00:23:48,960 --> 00:23:52,720 THINGS LIKE AMINO ACID UPTAKE, 714 00:23:52,720 --> 00:23:56,320 CRISPR CAS SYSTEMS FOR PHAGE 715 00:23:56,320 --> 00:23:57,120 DEFENSE, ET CETERA THAT, ARE 716 00:23:57,120 --> 00:24:00,600 SPECIFIC TO THE HUMAN GUT 717 00:24:00,600 --> 00:24:01,400 ASSOCIATED AND HUMAN MOUTH 718 00:24:01,400 --> 00:24:02,040 ASSOCIATED ORGANISMS. 719 00:24:02,040 --> 00:24:03,920 WE CAN DO THE REVERSE, WE CAN 720 00:24:03,920 --> 00:24:05,840 IDENTIFY CERTAIN KINDS OF 721 00:24:05,840 --> 00:24:07,160 CHARACTERISTICS OF CAPACITIES 722 00:24:07,160 --> 00:24:10,600 THAT ARE ABSENT IN HUMAN, AND 723 00:24:10,600 --> 00:24:12,680 JUST AS ONE EXAMPLE WOULD BE 724 00:24:12,680 --> 00:24:14,240 AEROBIC METABOLISM. 725 00:24:14,240 --> 00:24:16,400 SO THERE ARE SUBSTANTIAL CHANGES 726 00:24:16,400 --> 00:24:19,160 IN GENE CONTENT ASSOCIATED WITH 727 00:24:19,160 --> 00:24:20,840 ORGANISMS THAT HAVE COLONIZED 728 00:24:20,840 --> 00:24:21,240 THE HUMAN BODY. 729 00:24:21,240 --> 00:24:24,680 SO THE NEXT QUESTION WE CAN ASK 730 00:24:24,680 --> 00:24:27,640 IS, WHEN DID THESE CHANGES TAKE 731 00:24:27,640 --> 00:24:28,160 PLACE? 732 00:24:28,160 --> 00:24:29,720 ONE POSSIBILITY IS THAT THEY 733 00:24:29,720 --> 00:24:32,520 PRECEDED MIGRATION INTO THE 734 00:24:32,520 --> 00:24:38,640 HUMAN HABITAT, OROKURRED AROUNDD 735 00:24:38,640 --> 00:24:40,080 CONTINUOUSLY AFTER MIGRATION. 736 00:24:40,080 --> 00:24:42,640 THIS APPROACH, THE APPROACH TO 737 00:24:42,640 --> 00:24:43,760 ANALYZE THIS, REQUIRES THAT WE 738 00:24:43,760 --> 00:24:46,640 BUILD TREES FOR EVERY PROTEIN 739 00:24:46,640 --> 00:24:49,000 FAMILY AND COMPARE EACH TREE TO 740 00:24:49,000 --> 00:24:49,760 THE PHYLOGENETIC TREE. 741 00:24:49,760 --> 00:24:51,200 AND THAT CAN BE DONE MANUALLY 742 00:24:51,200 --> 00:24:53,400 AND WAS DONE BY ALEX TO SOME 743 00:24:53,400 --> 00:24:55,080 EXTENT MANUALLY, BUT BASICALLY 744 00:24:55,080 --> 00:24:59,400 THAT'S COMPUTATIONALLY TRACTABLE 745 00:24:59,400 --> 00:25:00,600 USING BIOINFORMATIC TOOLS. 746 00:25:00,600 --> 00:25:02,400 WE USE A TOOL DEVELOPED BY 747 00:25:02,400 --> 00:25:04,120 OTHERS CALLED THE ALE METHOD 748 00:25:04,120 --> 00:25:07,600 THAT BASICALLY DOES THIS IN A 749 00:25:07,600 --> 00:25:15,280 PROBABLISTIC KIND OF WAY, AND 750 00:25:15,280 --> 00:25:15,560 INFERENCES. 751 00:25:15,560 --> 00:25:16,920 THIS IS AN EXAMPLE OF THE KIND 752 00:25:16,920 --> 00:25:18,360 OF RESULTS YOU CAN GET. 753 00:25:18,360 --> 00:25:19,840 THESE ARE DOTS THAT ARE CODED 754 00:25:19,840 --> 00:25:21,640 FOR PROBABILITY THAT INDICATE 755 00:25:21,640 --> 00:25:25,000 THE INFERRED TIME OF ACQUISITION 756 00:25:25,000 --> 00:25:27,240 OF GAIN, SO VERY FEW GAINS 757 00:25:27,240 --> 00:25:29,680 ACTUALLY OR LOSS OF PROTEINS. 758 00:25:29,680 --> 00:25:31,240 OR PROTEIN FAMILIES, MORE 759 00:25:31,240 --> 00:25:31,680 ACCURATELY. 760 00:25:31,680 --> 00:25:34,840 SO FROM THIS, IT WOULD APPEAR, 761 00:25:34,840 --> 00:25:36,720 ANALYSIS OF THE DETAILS OF THESE 762 00:25:36,720 --> 00:25:37,840 KINDS OF PATTERNS WOULD APPEAR 763 00:25:37,840 --> 00:25:39,760 THAT THE GENE LOSSES DID NOT 764 00:25:39,760 --> 00:25:41,400 PRECEDE OR CO-OCCUR WITH 765 00:25:41,400 --> 00:25:42,400 MIGRATION INTO THE HUMAN BODY, 766 00:25:42,400 --> 00:25:44,880 BUT PROBABLY TOOK PLACE 767 00:25:44,880 --> 00:25:45,760 CONTINUOUSLY AFTER THE 768 00:25:45,760 --> 00:25:49,400 TRANSITION. 769 00:25:49,400 --> 00:25:50,640 SO WE CAN ANSWER A COUPLE OF 770 00:25:50,640 --> 00:25:51,600 QUESTIONS OR BEGIN TO ANSWER A 771 00:25:51,600 --> 00:25:53,280 COUPLE OF QUESTIONS FOR THESE 772 00:25:53,280 --> 00:25:55,400 GROUPS, AND THOSE ANSWERS WOULD 773 00:25:55,400 --> 00:25:58,840 BE THAT THE HABITAT TRANSITIONS 774 00:25:58,840 --> 00:26:00,960 ARE PROBABLY NOT ACCOMPANIED BY 775 00:26:00,960 --> 00:26:03,000 A HUGE CHANGE IN GENOME THAT 776 00:26:03,000 --> 00:26:05,640 OCCURRED AROUND THE TRANSITION 777 00:26:05,640 --> 00:26:07,880 TIME, BUT RATHER CONTINUOUSLY 778 00:26:07,880 --> 00:26:10,120 OVER TIME POST COLONIZATION, AND 779 00:26:10,120 --> 00:26:11,920 THAT THE COLONIZATION EVENTS 780 00:26:11,920 --> 00:26:13,160 PROBABLY HAPPENED MULTIPLE TIMES 781 00:26:13,160 --> 00:26:16,280 AND MOST LIKELY FROM 782 00:26:16,280 --> 00:26:18,400 GROUNDWATER-ASSOCIATED LINEAGES. 783 00:26:18,400 --> 00:26:22,200 SO THE CPR ARE JUST ONE EXAMPLE 784 00:26:22,200 --> 00:26:23,200 OF THIS BUT THERE ARE OTHER 785 00:26:23,200 --> 00:26:24,960 EXAMPLES WE CAN TURN TO SEE IF 786 00:26:24,960 --> 00:26:26,400 THE PATTERN HOLDS UP IN OTHER 787 00:26:26,400 --> 00:26:26,680 LINEAGES. 788 00:26:26,680 --> 00:26:27,800 I THINK THESE ARE INTERESTING 789 00:26:27,800 --> 00:26:28,600 GROUPS BECAUSE THREAR NOT THE 790 00:26:28,600 --> 00:26:30,960 ONES MOST PEOPLE WORK ON IN THE 791 00:26:30,960 --> 00:26:32,160 HUMAN MICROBIOME SO I'M REALLY 792 00:26:32,160 --> 00:26:33,760 FOCUSING ON CPR AND THESE TWO 793 00:26:33,760 --> 00:26:34,760 NEXT EXAMPLES. 794 00:26:34,760 --> 00:26:36,960 THE NEXT EXAMPLE IS ACTUALLY NOT 795 00:26:36,960 --> 00:26:39,840 A CANDIDATE PHYLUM, IT'S CALLED 796 00:26:39,840 --> 00:26:40,600 ELUSIMICROBIA AND I THINK 797 00:26:40,600 --> 00:26:42,160 THERE'S A COUPLE, MAYBE THREE 798 00:26:42,160 --> 00:26:45,720 ISOLATES AT THIS PRESENT TIME. 799 00:26:45,720 --> 00:26:48,240 THERE ARE ANALYSES THAT INDICATE 800 00:26:48,240 --> 00:26:48,920 THE GREAT DIVERSITY OF THESE 801 00:26:48,920 --> 00:26:50,320 THINGS AND ONLY RECENTLY HAVE WE 802 00:26:50,320 --> 00:26:54,160 BEEN ABLE TO ADD GENOMES FOR 803 00:26:54,160 --> 00:26:56,760 WHAT ARE INFERRED TO BE THE MOST 804 00:26:56,760 --> 00:26:57,000 LINEAGES. 805 00:26:57,000 --> 00:26:58,720 THE TOP HERE INDICATES THE 806 00:26:58,720 --> 00:27:03,360 PLACEMENT OF ELUSIMICROBIA WHERE 807 00:27:03,360 --> 00:27:05,440 IT FALLS IN THE TREE. 808 00:27:05,440 --> 00:27:07,040 THE CLOSEST GROUP YOU MIGHT BE 809 00:27:07,040 --> 00:27:09,440 FAMILIAR WITH ARE A CONVENTIONAL 810 00:27:09,440 --> 00:27:09,920 PHYLUM. 811 00:27:09,920 --> 00:27:11,200 HERE WEE COLLAPSED ALL THESE 812 00:27:11,200 --> 00:27:14,280 DOWN AND JUST OPENED UP THE 813 00:27:14,280 --> 00:27:15,240 ELUSIMICROBIA RADIATION. 814 00:27:15,240 --> 00:27:16,480 THE DIFFERENT LINEAGES ARE 815 00:27:16,480 --> 00:27:17,880 COLORED HERE ON THE TREE AND 816 00:27:17,880 --> 00:27:19,120 NUMBERED BUT THE MAIN POINT I 817 00:27:19,120 --> 00:27:20,840 WANT TO GET ACROSS NOW IS THE 818 00:27:20,840 --> 00:27:22,560 ENVIRONMENT OF ORIGIN OF THESE 819 00:27:22,560 --> 00:27:22,920 GENOMES. 820 00:27:22,920 --> 00:27:24,360 AND THEN WE HAVE A BIG SAMPLING 821 00:27:24,360 --> 00:27:26,080 OF THE GENOMES, WE CAN COMPARE 822 00:27:26,080 --> 00:27:28,360 THE ORGANISMS THAT HAVE COME 823 00:27:28,360 --> 00:27:31,120 FROM THE NATURAL ENVIRONMENTS TO 824 00:27:31,120 --> 00:27:33,240 THE ONES IN THE HUMAN/ANIMAL 825 00:27:33,240 --> 00:27:33,880 ASSOCIATED ENVIRONMENTS AND WE 826 00:27:33,880 --> 00:27:36,000 CODE THE ANIMAL-ASSOCIATED ONES 827 00:27:36,000 --> 00:27:37,920 IN THE OUTER RING, IN ORANGE, 828 00:27:37,920 --> 00:27:39,480 AND THEN JUST FOR EXAMPLE THE 829 00:27:39,480 --> 00:27:42,720 GROUNDWATER IN BLUE. 830 00:27:42,720 --> 00:27:44,920 SO FROM THIS, WE CAN SEE BY JUST 831 00:27:44,920 --> 00:27:45,680 FOCUSING ON THE ORANGE THAT 832 00:27:45,680 --> 00:27:47,440 THERE ARE AT LEAST TWO MAJOR 833 00:27:47,440 --> 00:27:50,840 GROUPS OF ELUSI MICROBIA THAT 834 00:27:50,840 --> 00:27:51,840 OCCUR IN THE HUMAN ENVIRONMENT 835 00:27:51,840 --> 00:27:52,920 AND IND KAIPTING THAT THERE'S 836 00:27:52,920 --> 00:27:56,920 BEEN AT LEAST TWO MIGRATION, TWO 837 00:27:56,920 --> 00:27:58,720 LINEAGES DIVERSIFIED INTO THE 838 00:27:58,720 --> 00:28:00,240 ANIMAL HABITAT AND THE CLOSEST 839 00:28:00,240 --> 00:28:05,960 FLANKING GROUPS OF GROUNDWATER. 840 00:28:05,960 --> 00:28:07,800 WE CAN ALSO LOOK AT THE GENE 841 00:28:07,800 --> 00:28:09,400 CONTENT FROM THE ANIMAL 842 00:28:09,400 --> 00:28:10,440 ASSOCIATED GROUPS AND THE ONES 843 00:28:10,440 --> 00:28:14,240 THAT HAD BEEN BEST ARE REALLY 844 00:28:14,240 --> 00:28:15,680 THESE HUMAN ASSOCIATED GROUPS 845 00:28:15,680 --> 00:28:17,960 REPRESENTED BY ISOLATES, THESE 846 00:28:17,960 --> 00:28:18,520 TWO. 847 00:28:18,520 --> 00:28:19,440 WE CAN MAKE A LIST OF THE 848 00:28:19,440 --> 00:28:20,480 FUNCTIONS THAT WE EXPECT TO FIND 849 00:28:20,480 --> 00:28:24,880 AND WE DO FIND IN GENOMES AND WE 850 00:28:24,880 --> 00:28:26,520 CAN COMPARE THAT SET OF 851 00:28:26,520 --> 00:28:27,400 FUNCTIONS AND BASICALLY THE 852 00:28:27,400 --> 00:28:28,480 TAKE-HOME POINT WITH THE BLUE 853 00:28:28,480 --> 00:28:30,560 SHADING INDICATES ENVIRONMENTAL 854 00:28:30,560 --> 00:28:32,520 SAMPLES, THE WHITE ARE THE HUMAN 855 00:28:32,520 --> 00:28:33,600 ASSOCIATED ONES, THAT THERE'S A 856 00:28:33,600 --> 00:28:35,160 SUBSTANTIAL LOSS IN METABOLIC 857 00:28:35,160 --> 00:28:37,000 DIVERSITY ASSOCIATED WITH THE 858 00:28:37,000 --> 00:28:38,640 HUMAN MICROBIOME COLONIZATION. 859 00:28:38,640 --> 00:28:42,200 WHICH IS REALLY NOT SURPRISING 860 00:28:42,200 --> 00:28:43,880 BECAUSE IT'S A MUCH MORE MAYBE 861 00:28:43,880 --> 00:28:49,720 NUTRIENT-RICH AND CONTROLLED 862 00:28:49,720 --> 00:28:50,480 ENVIRONMENT. 863 00:28:50,480 --> 00:28:53,200 THE THIRD GROUP WERE ORIGINALLY 864 00:28:53,200 --> 00:28:55,360 REPORTED AS BACTERIA ASSOCIATED 865 00:28:55,360 --> 00:28:57,280 WITH THE HUMAN GUT. 866 00:28:57,280 --> 00:29:00,080 YOU THINK, WHAT THE -- IS GOING 867 00:29:00,080 --> 00:29:00,520 ON HERE? 868 00:29:00,520 --> 00:29:02,240 CAN THAT BE TRUE? 869 00:29:02,240 --> 00:29:08,040 SO ACTUALLY I MET RUTH LAE, AND 870 00:29:08,040 --> 00:29:12,360 SHE TOLD ME ABOUT THESE 871 00:29:12,360 --> 00:29:13,520 CYANOBACTERIA, THEY TRIED TO GET 872 00:29:13,520 --> 00:29:15,520 SINGLE CELL GENOMES AND THEY 873 00:29:15,520 --> 00:29:16,280 COULDN'T GET ANY. 874 00:29:16,280 --> 00:29:18,120 THIS GOES BACK EARLY 2000s. 875 00:29:18,120 --> 00:29:23,280 I SAID, 1%, NO PROBLEM. 876 00:29:23,280 --> 00:29:24,640 GET US SOME SAMPLES AND WE'LL 877 00:29:24,640 --> 00:29:26,040 GET THE GENOMES. 878 00:29:26,040 --> 00:29:27,680 WE ACTUALLY GOT THREE -- I THINK 879 00:29:27,680 --> 00:29:30,720 THREE COMPLETE GENOMES. 880 00:29:30,720 --> 00:29:32,280 SHARON DID THE GENOMICS. 881 00:29:32,280 --> 00:29:33,400 AND WE COULD ADDRESS THE 882 00:29:33,400 --> 00:29:34,760 QUESTION OF WHAT THEY WERE DOING 883 00:29:34,760 --> 00:29:35,640 IN THE HUMAN GUT. 884 00:29:35,640 --> 00:29:37,640 WELL, IT TURNS OUT, AND I'M JUST 885 00:29:37,640 --> 00:29:38,840 PUTTING A LITTLE BIT HERE ABOUT 886 00:29:38,840 --> 00:29:40,040 WHY PEOPLE MIGHT CARE ABOUT IT, 887 00:29:40,040 --> 00:29:43,720 IT'S NOT MY FOCUS TODAY, IT 888 00:29:43,720 --> 00:29:45,240 TURNS OUT THEY'RE NOT PHOTO 889 00:29:45,240 --> 00:29:46,880 SYNTHETIC. 890 00:29:46,880 --> 00:29:47,920 ACTUALLY, IF YOU LOOK AT THE 891 00:29:47,920 --> 00:29:48,800 PHYLOGENY, I THINK MOST PEOPLE 892 00:29:48,800 --> 00:29:56,400 AGREE THEY'RE NOT SIGH CYANO. 893 00:29:56,400 --> 00:29:58,080 THE LINEAGE STRUCTURE OF THE 894 00:29:58,080 --> 00:30:00,480 TREE IS CHANGING PRETTY 895 00:30:00,480 --> 00:30:00,880 RADICALLY. 896 00:30:00,880 --> 00:30:04,320 THESE ARE THE CYANOBACTERIA. 897 00:30:04,320 --> 00:30:09,760 THIS IS A NEW GROUP WE CALL THE 898 00:30:09,760 --> 00:30:10,160 MELAINABACTERIA. 899 00:30:10,160 --> 00:30:11,600 IT WOULD APPEAR THAT THESE 900 00:30:11,600 --> 00:30:13,480 ORGANISMS ARE ACTUALLY 901 00:30:13,480 --> 00:30:16,120 FERMENTING IN THE GUT, AND 902 00:30:16,120 --> 00:30:20,920 PRETTY DISTINCTIVE, BASAL TO THE 903 00:30:20,920 --> 00:30:21,360 CYANOBACTERIA. 904 00:30:21,360 --> 00:30:25,600 THERE ARE TWO OTHER BASAL LINK 905 00:30:25,600 --> 00:30:26,960 YAJS AND THEY'RE ALSO 906 00:30:26,960 --> 00:30:28,160 FERMENTATION BASED METABOLISMS 907 00:30:28,160 --> 00:30:30,160 FOR THE MOST PART WITH A LOT OF 908 00:30:30,160 --> 00:30:31,440 HYDROGEN METABOLISM INVOLVED. 909 00:30:31,440 --> 00:30:32,720 BUT THAT'S REALLY I THINK MOSTLY 910 00:30:32,720 --> 00:30:34,280 INTERESTING FROM THE PERSPECTIVE 911 00:30:34,280 --> 00:30:42,120 OF EVOLUTION OF OXOGENIC 912 00:30:42,120 --> 00:30:42,520 PHOTOSYNTHESIS. 913 00:30:42,520 --> 00:30:44,160 WE CAN RENDER A CELL CARTOON. 914 00:30:44,160 --> 00:30:45,560 I DON'T EXPECT YOU TO READ THIS, 915 00:30:45,560 --> 00:30:46,560 UNDERSTAND IT, BUT I JUST WANT 916 00:30:46,560 --> 00:30:49,600 TO SHOW THAT ALL THE GENES AND 917 00:30:49,600 --> 00:30:51,280 PATHWAYS, PARTICULARLY YOU'VE 918 00:30:51,280 --> 00:30:52,800 GOT A GENOME THAT'S REALLY HIGH 919 00:30:52,800 --> 00:30:54,320 QUALITY OR COMPLEELT CAN BE USED 920 00:30:54,320 --> 00:30:56,520 TO DO A RECONSTRUCTION OF THE 921 00:30:56,520 --> 00:30:57,040 METABOLISM. 922 00:30:57,040 --> 00:30:59,160 AND THIS IS THE KIND OF WAY WE 923 00:30:59,160 --> 00:31:00,440 PRESENT IT, YOU'LL FIND THESE 924 00:31:00,440 --> 00:31:02,000 VERY COMMONLY ALSO IN ISOLATE 925 00:31:02,000 --> 00:31:03,960 GENOMES, SO IT'S BASICALLY VERY 926 00:31:03,960 --> 00:31:05,480 ANALOGOUS TO THE KIND OF 927 00:31:05,480 --> 00:31:06,640 RENDERING OF DATA THAT WE WOULD 928 00:31:06,640 --> 00:31:10,960 USE THERE. 929 00:31:10,960 --> 00:31:12,720 SO WE CAN TO THE SAME KIND OF 930 00:31:12,720 --> 00:31:14,920 ANALYSIS, WE CAN ASK ABOUT 931 00:31:14,920 --> 00:31:16,760 PROTEIN FAMILIES, WE CAN ASK 932 00:31:16,760 --> 00:31:17,400 ABOUT ENVIRONMENTAL ORIGIN. 933 00:31:17,400 --> 00:31:21,600 THESE ARE LINES, ROWS OF 934 00:31:21,600 --> 00:31:22,400 GENOMES, THEY'RE GROUPED BY 935 00:31:22,400 --> 00:31:23,880 ENVIRONMENT AND THEN THE COLUMNS 936 00:31:23,880 --> 00:31:24,640 ARE CAPACITIES. 937 00:31:24,640 --> 00:31:25,840 THIS IS A SLIGHTLY DIFFERENT WAY 938 00:31:25,840 --> 00:31:27,800 OF PRESENTING THE DATA, THE 939 00:31:27,800 --> 00:31:30,040 GENOME COMPLETENESS, ONE IN A 940 00:31:30,040 --> 00:31:33,440 BOX MEANS IT'S GOT ONE -- 941 00:31:33,440 --> 00:31:35,040 THEY'RE ALL REALLY GOOD QUALITY 942 00:31:35,040 --> 00:31:35,600 GENOMES. 943 00:31:35,600 --> 00:31:38,080 PRETTY CLEARLY, THE GENETIC 944 00:31:38,080 --> 00:31:44,520 CAPACITIES OF THE GUT ASSOCIATED 945 00:31:44,520 --> 00:31:45,880 MELANABACTERIA ARE PRETTY 946 00:31:45,880 --> 00:31:47,840 SUBSTANTIALLY LESS THAN THOSE OF 947 00:31:47,840 --> 00:31:48,720 THEIR ENVIRONMENTAL 948 00:31:48,720 --> 00:31:49,800 COUNTERPARTS, AGAIN POINTING TO 949 00:31:49,800 --> 00:31:53,960 THIS IDEA OF GENE REPERTOIRE 950 00:31:53,960 --> 00:31:55,760 LOSS IN GENOME REDUCTION 951 00:31:55,760 --> 00:32:00,560 ASSOCIATED WITH HUMAN 952 00:32:00,560 --> 00:32:00,880 COLONIZATION. 953 00:32:00,880 --> 00:32:02,520 I WANT TO TALK TO YOU ABOUT 954 00:32:02,520 --> 00:32:04,360 PHAGES BECAUSE I'VE BEEN VERY 955 00:32:04,360 --> 00:32:05,840 INTERESTED IN THE VIRUSES IN 956 00:32:05,840 --> 00:32:07,000 BACTERIA FOR QUITE A WHILE. 957 00:32:07,000 --> 00:32:08,520 ACTUALLY SOME OF THE MOST 958 00:32:08,520 --> 00:32:09,440 INTERESTING ONES TURN OUT TO BE 959 00:32:09,440 --> 00:32:16,520 THE ONES FROM THE HUMAN 960 00:32:16,520 --> 00:32:17,600 MICROBIOME. 961 00:32:17,600 --> 00:32:18,800 IF YOU LOOK AT THE AVERAGE SIZE 962 00:32:18,800 --> 00:32:20,280 OF PHAGE GENOMES IN PUBLIC DATA, 963 00:32:20,280 --> 00:32:23,560 AT LEAST WHEN WE DID IN 2019, IT 964 00:32:23,560 --> 00:32:27,880 WAS 55KB, WHICH IS PRETTY TINY. 965 00:32:27,880 --> 00:32:30,560 BUT WHEN WE WERE WORKING ON A 966 00:32:30,560 --> 00:32:33,600 PARTICULAR COHORT OF INDIVIDUALS 967 00:32:33,600 --> 00:32:35,800 FROM BANGLADESH, IT CAME TO 968 00:32:35,800 --> 00:32:37,080 LIGHT THAT THERE WERE SOME 969 00:32:37,080 --> 00:32:39,240 REALLY HUGE GENOMES IN THERE, 970 00:32:39,240 --> 00:32:40,600 MUCH BIGGER THAN WE HAD REALLY 971 00:32:40,600 --> 00:32:43,200 EXPECTED. 972 00:32:43,200 --> 00:32:45,160 AND ALL OF THESE WERE MANUALLY 973 00:32:45,160 --> 00:32:48,320 CURE WRAITED TO 974 00:32:48,320 --> 00:32:49,520 CURATED TO COMPLETION, IT'S 975 00:32:49,520 --> 00:32:52,600 ACTUALLY A HANDFUL OF INDIVIDUAL 976 00:32:52,600 --> 00:32:53,600 SUBJECTS, BUT THE BIGGEST ARE 977 00:32:53,600 --> 00:32:56,200 THE MOST INTERESTING, PERHAPS 978 00:32:56,200 --> 00:32:59,840 THOSE ARE AROUND 540 AND SOME A 979 00:32:59,840 --> 00:33:07,560 LITTLE LARGER NOW, SO ROUGHLY 10 980 00:33:07,560 --> 00:33:09,040 TIMES BIGGER THAN EXPECTED, 981 00:33:09,040 --> 00:33:10,240 BASED ON PUBLIC DATA. 982 00:33:10,240 --> 00:33:13,240 SO LET'S TAKE A LOOK AT THESE 983 00:33:13,240 --> 00:33:14,880 TWO GENOMES, OR THE GROUP OF 984 00:33:14,880 --> 00:33:16,320 GENOMES THAT THESE TWO GENOMES 985 00:33:16,320 --> 00:33:17,560 REPRESENT. 986 00:33:17,560 --> 00:33:19,280 BECAUSE THEY ARE SO DISTINCTIVE, 987 00:33:19,280 --> 00:33:21,280 WE GAVE THEM A NAME AND THE NAME 988 00:33:21,280 --> 00:33:22,160 COMES FROM THE NAME OF THE 989 00:33:22,160 --> 00:33:24,560 VILLAGE WHERE THESE SUBJECTS 990 00:33:24,560 --> 00:33:25,560 WERE RECRUITED, HUMAN SUBJECTS. 991 00:33:25,560 --> 00:33:28,720 AND SO WE CALLED THEM THE LAK 992 00:33:28,720 --> 00:33:29,480 PHAGES. 993 00:33:29,480 --> 00:33:33,840 SO THESE ARE THE FIRST TWO 994 00:33:33,840 --> 00:33:34,960 CLAVES, A1 AND A2. 995 00:33:34,960 --> 00:33:36,520 FIRST LET ME JUST ASK, WHY DOES 996 00:33:36,520 --> 00:33:38,040 IT MATTER THAT PHAGES HAVE LARGE 997 00:33:38,040 --> 00:33:38,520 GENOMES? 998 00:33:38,520 --> 00:33:39,800 FIRST OF ALL, IT'S NOT EXPECTED 999 00:33:39,800 --> 00:33:42,160 SO THERE'S GOT TO BE SOMETHING 1000 00:33:42,160 --> 00:33:43,880 INTERESTING THERE, A WAY OF 1001 00:33:43,880 --> 00:33:44,840 BEING FOR A PHAGE. 1002 00:33:44,840 --> 00:33:46,200 WE MIGHT ANTICIPATE BECAUSE OF 1003 00:33:46,200 --> 00:33:48,800 THEIR SUBSTANTIAL GENETIC 1004 00:33:48,800 --> 00:33:50,280 REPERTOIRES, THEY MAY BEHAVE 1005 00:33:50,280 --> 00:33:51,000 DIFFERENTLY DURING INFECTION. 1006 00:33:51,000 --> 00:33:52,080 PEOPLE HAVE SUGGESTED MAYBE THEY 1007 00:33:52,080 --> 00:33:54,160 DON'T ACTUALLY DO ANYTHING, THEY 1008 00:33:54,160 --> 00:33:55,480 JUST HANG OUT ALMOST LIKE A 1009 00:33:55,480 --> 00:33:56,000 PLASMID. 1010 00:33:56,000 --> 00:33:57,000 WE DON'T KNOW THAT TO BE THE 1011 00:33:57,000 --> 00:33:59,720 CASE. 1012 00:33:59,720 --> 00:34:03,320 THEIR LARGE CARGO CAPACITIES IS 1013 00:34:03,320 --> 00:34:04,040 POTENTIALLY MEDICALLY RELEVANT 1014 00:34:04,040 --> 00:34:05,560 AS WELL AS BIOLOGICALLY RELEVANT 1015 00:34:05,560 --> 00:34:06,760 FROM THE PERSPECTIVE OF THEIR -- 1016 00:34:06,760 --> 00:34:08,720 I DON'T WANT TO SAY LIFESTYLES, 1017 00:34:08,720 --> 00:34:10,000 BUT EXISTENCE STYLES, AND I 1018 00:34:10,000 --> 00:34:15,040 WOULD JUST NOTE THAT THE MEDICAL 1019 00:34:15,040 --> 00:34:16,320 IMPORTANCE ASSOCIATED WITH BEING 1020 00:34:16,320 --> 00:34:18,080 ABLE TO TRANSFER MANY GENES MAY 1021 00:34:18,080 --> 00:34:19,240 COME ABOUT THROUGH THE ABILITY 1022 00:34:19,240 --> 00:34:21,160 TO MOVE ANTIBIOTIC RESISTANCE 1023 00:34:21,160 --> 00:34:22,440 GENES AND VIRULENCE FACTORS. 1024 00:34:22,440 --> 00:34:26,280 I THINK MOST PEOPLE DON'T THINK 1025 00:34:26,280 --> 00:34:29,040 ABOUT PHAGE SPREAD OF DISEASE 1026 00:34:29,040 --> 00:34:30,280 BETWEEN ANIMAL HUMAN WISE 1027 00:34:30,280 --> 00:34:33,320 BECAUSE THEY'RE ALL FOCUSED ON 1028 00:34:33,320 --> 00:34:34,520 VIRUSES OF EUKARYOTES. 1029 00:34:34,520 --> 00:34:36,720 I THINK THERE'S ACTUALLY A KIND 1030 00:34:36,720 --> 00:34:37,800 OF PARALLEL PHENOMENON THAT 1031 00:34:37,800 --> 00:34:38,840 MIGHT BE POSSIBLE HERE, IN THE 1032 00:34:38,840 --> 00:34:43,320 CASE WHERE THE PHAGES CARRY IN 1033 00:34:43,320 --> 00:34:45,920 PENNSYLVANIA 1034 00:34:45,920 --> 00:34:47,880 TOXINS THAT MAKE THE MICROBES 1035 00:34:47,880 --> 00:34:48,400 PATHOGENIC. 1036 00:34:48,400 --> 00:34:51,360 THIS IS JUST A LITTLE LIST OF 1037 00:34:51,360 --> 00:34:54,440 DISEASES THAT ARE INTRODUCED 1038 00:34:54,440 --> 00:34:55,440 INTO HUMANS BY THAT MECHANISM. 1039 00:34:55,440 --> 00:34:57,480 SO IT'S ACTUALLY A PRETTY GOOD 1040 00:34:57,480 --> 00:34:58,000 LIST. 1041 00:34:58,000 --> 00:35:00,360 AND SO THIS RAISES A QUESTION 1042 00:35:00,360 --> 00:35:01,920 THAT I THINK IS PRETTY 1043 00:35:01,920 --> 00:35:03,480 UNDERSTUDIED THAT POINT IS, 1044 00:35:03,480 --> 00:35:04,800 COULD MIGRATION OF PHAGES FROM 1045 00:35:04,800 --> 00:35:06,480 ANIMALS INTO THE HUMAN 1046 00:35:06,480 --> 00:35:08,520 MICROBIOME ACTUALLY BE A 1047 00:35:08,520 --> 00:35:09,520 MECHANISM FOR TRANSFER OF 1048 00:35:09,520 --> 00:35:11,920 DISEASE? 1049 00:35:11,920 --> 00:35:13,200 AND I PARTLY MAYBE CAN ANSWER A 1050 00:35:13,200 --> 00:35:14,840 LITTLE BIT OF WHY THAT MIGHT NOT 1051 00:35:14,840 --> 00:35:16,400 BE AS TRUE AS I'D ORIGINALLY 1052 00:35:16,400 --> 00:35:18,640 THOUGHT IN THE COMING SLIDES. 1053 00:35:18,640 --> 00:35:20,080 SO THE NEXT QUESTION WE HAVE IS, 1054 00:35:20,080 --> 00:35:23,720 WELL, OKAY, WE'VE GOT THESE HUGE 1055 00:35:23,720 --> 00:35:25,840 PHAGES IN THE HUMAN MICROBIOME, 1056 00:35:25,840 --> 00:35:28,120 WHAT DO THEY REPLICATE IN? 1057 00:35:28,120 --> 00:35:29,520 THE ANSWER AS INFORM BID CRISPR 1058 00:35:29,520 --> 00:35:30,640 SPACE, I WON'T GO INTO THE 1059 00:35:30,640 --> 00:35:35,800 DETAILS, IS VERY CLEARLY 1060 00:35:35,800 --> 00:35:37,160 PREVOTELLA. 1061 00:35:37,160 --> 00:35:42,560 RS THE THE REPRESENTATION IS N 1062 00:35:42,560 --> 00:35:44,920 THESE GOLD COLORS, IT'S THE MOST 1063 00:35:44,920 --> 00:35:45,840 ABUNDANT GENUS. 1064 00:35:45,840 --> 00:35:47,120 AND THESE INDIVIDUAL LITTLE 1065 00:35:47,120 --> 00:35:49,040 BLOCKS WITHIN THE BAR ARE ACTUAL 1066 00:35:49,040 --> 00:35:51,600 GENOMES. 1067 00:35:51,600 --> 00:35:54,000 SO MANY DIFFERENT SPECIES OF 1068 00:35:54,000 --> 00:35:54,520 PREVOTELLA. 1069 00:35:54,520 --> 00:35:55,320 ONE OF THE THINGS THAT CAUGHT 1070 00:35:55,320 --> 00:35:57,440 OUR EYE IMMEDIATELY PONZIING 1071 00:35:57,440 --> 00:36:00,800 THESE HUGE GENES, GENOMES, I BEG 1072 00:36:00,800 --> 00:36:01,640 YOUR PARDON, IS THE FACT THAT 1073 00:36:01,640 --> 00:36:05,400 WHEN WE PREDICTED THE GENES, THE 1074 00:36:05,400 --> 00:36:06,840 PREDICTIONS JUST LOOKED 1075 00:36:06,840 --> 00:36:08,360 COMPLETELY WRONG. 1076 00:36:08,360 --> 00:36:11,280 NORMALLY THEY HAVE ABOUT 90% 1077 00:36:11,280 --> 00:36:13,520 PLUS CODING DENSITY, AND THESE 1078 00:36:13,520 --> 00:36:17,400 HAD UP TO 50% REGIONS WHICH 1079 00:36:17,400 --> 00:36:18,320 PRETTY MUCH TELLS YOU SOMETHING 1080 00:36:18,320 --> 00:36:23,600 IS WRONG. 1081 00:36:23,600 --> 00:36:24,480 MOREOVER, GENES THAT YOU WOULD 1082 00:36:24,480 --> 00:36:26,320 HAVE EXPECTED TO BE MADE OF 1083 00:36:26,320 --> 00:36:27,640 THESE TWO PARTS WERE FRAGMENTED, 1084 00:36:27,640 --> 00:36:29,280 SUGGESTING THAT SOMETHING WAS 1085 00:36:29,280 --> 00:36:31,240 WRONG IN THE GENE CALLING. 1086 00:36:31,240 --> 00:36:33,160 THE ANSWER, AS HAS ALSO BEEN 1087 00:36:33,160 --> 00:36:36,080 SEEN IN THE CPR BACTERIA I 1088 00:36:36,080 --> 00:36:37,240 MENTIONED, THE BACTERIAL TYPES, 1089 00:36:37,240 --> 00:36:40,840 AND IN ONE PRIOR STUDY IN A BIG 1090 00:36:40,840 --> 00:36:42,480 SURVEY JGI DID IS THAT THE 1091 00:36:42,480 --> 00:36:44,960 PHAGES USE AN ALTERNATE GENETIC 1092 00:36:44,960 --> 00:36:45,320 CODE. 1093 00:36:45,320 --> 00:36:47,400 AND IT'S NOT COMPLETELY 1094 00:36:47,400 --> 00:36:48,840 MYSTERIOUS, IT'S JUST SIMILARLY 1095 00:36:48,840 --> 00:36:53,040 THAT A STOP CODON HAS BEEN 1096 00:36:53,040 --> 00:36:54,200 RE-ASSIGNED FROM AN AMINO ACID. 1097 00:36:54,200 --> 00:36:55,880 WHEN WE TELL THE PROGRAM THIS 1098 00:36:55,880 --> 00:36:57,200 PARTICULAR STOP CODON, WHICH I'M 1099 00:36:57,200 --> 00:36:59,800 GOING TO REFER TO AS TAG OR UAG 1100 00:36:59,800 --> 00:37:01,200 AS YOU PREFER, IS NOT REALLY A 1101 00:37:01,200 --> 00:37:02,520 STOP CODON. 1102 00:37:02,520 --> 00:37:03,760 IT'S AN AMINO ACID. 1103 00:37:03,760 --> 00:37:06,000 AND WHEN WE TELL THE PROGRAM 1104 00:37:06,000 --> 00:37:07,440 THAT AND WE DO THE GENE 1105 00:37:07,440 --> 00:37:10,320 PREDICTIONS, YOU CAN SEE WE 1106 00:37:10,320 --> 00:37:12,080 RECOVER GOOD CODING DENSITY AND 1107 00:37:12,080 --> 00:37:13,080 FULL PROTEIN PREDICTIONS. 1108 00:37:13,080 --> 00:37:16,520 SO PRETTY CLEARLY, THE CODE OF 1109 00:37:16,520 --> 00:37:19,320 THE PREVOTELLA AND OF THE PHAGE 1110 00:37:19,320 --> 00:37:21,200 THAT AFFECTS IT, THIS PHAGE THAT 1111 00:37:21,200 --> 00:37:22,360 AFFECTS IT OR THIS GROUP OF 1112 00:37:22,360 --> 00:37:23,480 PHAGES IS DIFFERENT, WHICH 1113 00:37:23,480 --> 00:37:25,000 RAISES ALL SORTS OF INTERESTING 1114 00:37:25,000 --> 00:37:26,440 QUESTIONS WHEN IT COME TO 1115 00:37:26,440 --> 00:37:26,760 TRANSLATION. 1116 00:37:26,760 --> 00:37:29,080 SO YOU'VE GOT ONE RIBOSOME AND 1117 00:37:29,080 --> 00:37:29,960 TWO GENETIC CODES FEEDING IN, 1118 00:37:29,960 --> 00:37:30,800 HOW DOES THAT WORK AND WHY WOULD 1119 00:37:30,800 --> 00:37:33,480 THAT BE THE CASE? 1120 00:37:33,480 --> 00:37:35,560 SO JUST TO MAKE THAT REALLY 1121 00:37:35,560 --> 00:37:39,200 CLEAR, A STOP CODON IS NOW READ 1122 00:37:39,200 --> 00:37:41,240 THROUGH AND AN AMINO ACID IS 1123 00:37:41,240 --> 00:37:42,000 INCORPORATED, SO THE NEXT 1124 00:37:42,000 --> 00:37:44,000 QUESTION MIGHT BE WHAT AMINO 1125 00:37:44,000 --> 00:37:44,880 ACID? 1126 00:37:44,880 --> 00:37:47,280 I SHOULD SAY THERE'S THREE STOP 1127 00:37:47,280 --> 00:37:48,240 CODONS. 1128 00:37:48,240 --> 00:37:49,760 TAG, TGA AND TAA. 1129 00:37:49,760 --> 00:37:52,200 IT TURNS OUT NOBODY'S EVER FOUND 1130 00:37:52,200 --> 00:37:54,960 TAA RE-ASSIGNED, BUT BOTH TAG 1131 00:37:54,960 --> 00:37:59,320 AND TGA CAN BE RE-ASSIGNED, SO 1132 00:37:59,320 --> 00:38:01,400 IT CAN JUST CODE FOR AMINO ACID. 1133 00:38:01,400 --> 00:38:02,960 SO WE CAN MAKE ALIGNMENTS OF THE 1134 00:38:02,960 --> 00:38:04,040 VARIOUS SEQUENCES OF THESE 1135 00:38:04,040 --> 00:38:07,800 PHAGES, AND BY LOOKING AT THE 1136 00:38:07,800 --> 00:38:08,800 AMINO ACID CODED FOR IN THE 1137 00:38:08,800 --> 00:38:10,320 POSITION THAT'S NOW READING IN A 1138 00:38:10,320 --> 00:38:11,440 WAY THAT WE WOULD THINK TO MEAN 1139 00:38:11,440 --> 00:38:13,920 STOP, WE CAN FIGURE OUT THAT THE 1140 00:38:13,920 --> 00:38:18,080 UAG IS TRANSLATED AS GLUTAMINE. 1141 00:38:18,080 --> 00:38:19,680 SO WHEN WE LOOK AT THE 1142 00:38:19,680 --> 00:38:22,040 DISTRIBUTION OF RE-ASSIGNED STOP 1143 00:38:22,040 --> 00:38:23,520 CODONS ACROSS THE GENOMES, ONE 1144 00:38:23,520 --> 00:38:25,000 THING THAT BECAME REALLY OBVIOUS 1145 00:38:25,000 --> 00:38:28,120 IN THESE LAK PHAGES IS THAT IT'S 1146 00:38:28,120 --> 00:38:28,680 REALLY HETEROGENEOUS. 1147 00:38:28,680 --> 00:38:30,440 SOME GENES HAD NO RE-ASSIGNED 1148 00:38:30,440 --> 00:38:31,280 CODON, OTHERS HAD MANY. 1149 00:38:31,280 --> 00:38:32,680 AND IF WE LOOK AT THE CATEGORIES 1150 00:38:32,680 --> 00:38:35,200 OF GENES THAT HAVE MANY STOP 1151 00:38:35,200 --> 00:38:36,720 CODON, IT'S ALL THE STRUCTURAL 1152 00:38:36,720 --> 00:38:37,800 PROTEINS. 1153 00:38:37,800 --> 00:38:39,800 AND LATE STAGE PROTEINS. 1154 00:38:39,800 --> 00:38:40,800 I'LL COME BACK TO THAT IN A 1155 00:38:40,800 --> 00:38:42,840 MOMENT. 1156 00:38:42,840 --> 00:38:46,160 SO WE ASKED, WELL, WHERE WE FIND 1157 00:38:46,160 --> 00:38:52,520 THESE LAQ PHAGES AND LAE 1158 00:38:52,520 --> 00:38:55,040 FIND CERTAIN KINDS OF 1159 00:38:55,040 --> 00:38:55,520 PREVOTELLA. 1160 00:38:55,520 --> 00:39:02,800 IN WESTERN DIET, THE BACK BAS 1161 00:39:02,800 --> 00:39:03,040 GENUS. 1162 00:39:03,040 --> 00:39:06,360 IN THE U.S. WE FIND ALMOST NONE 1163 00:39:06,360 --> 00:39:11,480 AND WE FIND THE LAK PHAGES IN 1164 00:39:11,480 --> 00:39:14,360 PREVOTELLA AND BABOONS, HUNTER 1165 00:39:14,360 --> 00:39:15,000 GATHERER COMMUNITIES, CHILDREN 1166 00:39:15,000 --> 00:39:19,800 FROM INDIA AND CHOLERA-IMPACTED 1167 00:39:19,800 --> 00:39:20,520 BANGLADESHIS AND SO FORTH. 1168 00:39:20,520 --> 00:39:23,120 SO WE ASKED, THEN, OKAY, LET'S 1169 00:39:23,120 --> 00:39:25,080 LOOK AT LAK PHAGES MORE BROADLY 1170 00:39:25,080 --> 00:39:28,920 AND SO WE DELIBERATELY COLLECTED 1171 00:39:28,920 --> 00:39:31,120 A TON OF DIFFERENT ANIMAL 1172 00:39:31,120 --> 00:39:33,040 MICROBIOME SAMPLES AND MADE A 1173 00:39:33,040 --> 00:39:37,040 PHYLOGENIC TREE IN WHICH WE 1174 00:39:37,040 --> 00:39:38,720 REPRESENT EACH GENOME AS A 1175 00:39:38,720 --> 00:39:40,200 BRANCH AND WE CODE THE BRANCHES 1176 00:39:40,200 --> 00:39:41,560 BY ORGANISM OF ORIGIN. 1177 00:39:41,560 --> 00:39:43,040 SO ANIMAL ORGANISM OF ORIGIN. 1178 00:39:43,040 --> 00:39:44,720 WE CAN SEE HERE, FOR EXAMPLE, IN 1179 00:39:44,720 --> 00:39:47,920 THIS BRANCH ON THE RIGHT, WE 1180 00:39:47,920 --> 00:39:49,600 HAVE MANY GREEN AND YELLOW DOTS. 1181 00:39:49,600 --> 00:39:52,080 THESE ARE ALL BABOON-ASSOCIATED 1182 00:39:52,080 --> 00:39:52,360 ORGANISMS. 1183 00:39:52,360 --> 00:39:53,360 HERE INTERESTINGLY ENOUGH, WE 1184 00:39:53,360 --> 00:39:55,320 HAVE GREEN AND PINK AND BLUE 1185 00:39:55,320 --> 00:39:57,360 WHICH ARE A MIXTURE OF HUMANS 1186 00:39:57,360 --> 00:40:00,680 AND QUITE DISTANTLY RELATED 1187 00:40:00,680 --> 00:40:01,440 ORGANISMS, WHICH WOULD BE PIGS 1188 00:40:01,440 --> 00:40:04,680 AND HORSES, SO DOMESTICATED 1189 00:40:04,680 --> 00:40:04,920 ANIMALS. 1190 00:40:04,920 --> 00:40:06,320 BY THE WAY, THE LARGEST GENOME 1191 00:40:06,320 --> 00:40:09,400 IS NOW 660KB, SO FOR A 1192 00:40:09,400 --> 00:40:10,400 HUMAN-ASSOCIATED ORGANISM. 1193 00:40:10,400 --> 00:40:11,800 WE CAN ASK NOW THE SAME KIND OF 1194 00:40:11,800 --> 00:40:13,760 QUESTION ABOUT PROTEIN FAMILIES 1195 00:40:13,760 --> 00:40:15,880 BY MAKING EXACTLY THE KIND OF -- 1196 00:40:15,880 --> 00:40:18,200 SAME KIND OF ARRAY I SHOWED YOU 1197 00:40:18,200 --> 00:40:20,200 BEFORE BUT HERE CODING PRESENCE 1198 00:40:20,200 --> 00:40:20,680 IS GREY. 1199 00:40:20,680 --> 00:40:22,360 WE CAN SEE THERE ARE GROUPS OF 1200 00:40:22,360 --> 00:40:23,000 PROTEIN FAMILIES THAT ARE 1201 00:40:23,000 --> 00:40:25,240 SPECIFIC TO PHAGES THAT ARE 1202 00:40:25,240 --> 00:40:26,720 FOUND IN DIFFERENT MICROBIOME 1203 00:40:26,720 --> 00:40:28,640 TYPES. 1204 00:40:28,640 --> 00:40:32,320 SO FOR EXAMPLE, WE CAN PUT BOXES 1205 00:40:32,320 --> 00:40:33,760 AROUND PROTEIN FAMILIES THAT ARE 1206 00:40:33,760 --> 00:40:35,360 SPECIFIC TO PIGS AND THEN 1207 00:40:35,360 --> 00:40:36,680 PROTEIN FAMILIES THAT ARE 1208 00:40:36,680 --> 00:40:38,120 SPECIFIC TO ALL BABOONS AND SOME 1209 00:40:38,120 --> 00:40:39,680 KINDS OF BABOONS AND OTHER KINDS 1210 00:40:39,680 --> 00:40:40,440 OF BABOONS. 1211 00:40:40,440 --> 00:40:42,720 SO THIS ACTUALLY TELLS US THAT 1212 00:40:42,720 --> 00:40:45,280 PROBABLY IF NOT IMMEDIATELY UPON 1213 00:40:45,280 --> 00:40:46,800 MIGRATION, OVER TIME AFTER 1214 00:40:46,800 --> 00:40:47,840 MIGRATION OF THE PHAGES AND 1215 00:40:47,840 --> 00:40:49,240 PROBABLY THE BACTERIAL HOSTS 1216 00:40:49,240 --> 00:40:51,320 INTO THESE NULL OR DIFFERENT 1217 00:40:51,320 --> 00:40:53,720 ANIMAL MICROBIOMES, THERE'S BEEN 1218 00:40:53,720 --> 00:40:55,520 PRETTY SUBSTANTIAL CHANGES IN 1219 00:40:55,520 --> 00:41:00,720 GENE CAPACITIES. 1220 00:41:00,720 --> 00:41:02,040 SO I THINK I'M GOING TO SKIP 1221 00:41:02,040 --> 00:41:04,880 THIS SLIDE ON THE ORDER OF TIME 1222 00:41:04,880 --> 00:41:08,920 BUT SAY VERY BRIEFLY THAT THESE 1223 00:41:08,920 --> 00:41:11,600 LIVE PHAGES ARE NOT RARE AND THE 1224 00:41:11,600 --> 00:41:13,440 CODING STUDY IS NOT RARE. 1225 00:41:13,440 --> 00:41:15,120 NEXT I'LL TALK ABOUT THE LARGER 1226 00:41:15,120 --> 00:41:17,840 ANALYSIS OF THE CODED PHAGES NOT 1227 00:41:17,840 --> 00:41:18,960 JUST LIMITED TO LAK. 1228 00:41:18,960 --> 00:41:21,200 LOTS OF -- THIS IS JUST 10 1229 00:41:21,200 --> 00:41:22,240 SAMPLES, LOTS AND LOTS OF 1230 00:41:22,240 --> 00:41:24,320 INSTANCES OF BIG GENOMES AND 1231 00:41:24,320 --> 00:41:25,840 ALTERNATE CODED PHAGES THAT ARE 1232 00:41:25,840 --> 00:41:26,880 QUITE ABUNDANT. 1233 00:41:26,880 --> 00:41:29,200 SO WE CONDUCTED A STUDY 1234 00:41:29,200 --> 00:41:33,080 PUBLISHED RECENTLY IN WHICH WE 1235 00:41:33,080 --> 00:41:35,200 BASICALLY SURVEYED ANIMAL AND 1236 00:41:35,200 --> 00:41:36,520 HUMAN MICROBIOMES AND WE 1237 00:41:36,520 --> 00:41:38,840 BASICALLY CLASSIFIED EACH OF THE 1238 00:41:38,840 --> 00:41:40,960 PHAGE GENOMES BASED ON WHETHER 1239 00:41:40,960 --> 00:41:44,320 OR NOT TAG OR TGA WAS 1240 00:41:44,320 --> 00:41:45,440 RE-ASSIGNED. 1241 00:41:45,440 --> 00:41:47,480 AND WE FIND BOTH. 1242 00:41:47,480 --> 00:41:49,320 AND WE FIND THAT THE GENOMES 1243 00:41:49,320 --> 00:41:50,920 HAVE QUITE A WIDE DISTRIBUTION 1244 00:41:50,920 --> 00:41:52,040 OF LENGTH SO IT'S NOT JUST 1245 00:41:52,040 --> 00:41:53,520 ASSOCIATED WITH BIG GENOMES. 1246 00:41:53,520 --> 00:41:57,480 AND THAT IT VARIES QUITE A BIT, 1247 00:41:57,480 --> 00:42:00,600 AND IT'S VERY SUBSTANTIALLY MORE 1248 00:42:00,600 --> 00:42:02,560 PREVALENT IN HUMANS WITH A 1249 00:42:02,560 --> 00:42:03,680 NON-WESTERN DIET COMPARED TO 1250 00:42:03,680 --> 00:42:05,400 WESTERN DIET. 1251 00:42:05,400 --> 00:42:07,000 SO I WON'T GO INTO THIS IN 1252 00:42:07,000 --> 00:42:08,400 DETAIL, BUT THIS IS A PHYLOGENIC 1253 00:42:08,400 --> 00:42:10,040 TREE THAT BASICALLY ON THE 1254 00:42:10,040 --> 00:42:13,240 OUTSIDE IS DECORATED WITH BARS 1255 00:42:13,240 --> 00:42:14,080 TO INDICATE GENOME LENGTH. 1256 00:42:14,080 --> 00:42:15,520 SO AGAIN, YOU CAN SEE 1257 00:42:15,520 --> 00:42:17,800 SUBSTANTIAL DIFFERENCES IN 1258 00:42:17,800 --> 00:42:19,960 GENOME LENGTH. 1259 00:42:19,960 --> 00:42:21,160 AND SHOWN IN THE COLORS HERE, 1260 00:42:21,160 --> 00:42:23,720 JUST AS THESE BLOCKS OF COLORS 1261 00:42:23,720 --> 00:42:26,840 ARE THE DIFFERENT -- WE FIND 1262 00:42:26,840 --> 00:42:28,840 FOUR DISTINCT FAMILIES OF 1263 00:42:28,840 --> 00:42:33,800 ALTERNATIVELY RE-CODED 1264 00:42:33,800 --> 00:42:35,840 BACTERIOPHAGES, THAT INFECT 1265 00:42:35,840 --> 00:42:36,280 FIRMICUTES. 1266 00:42:36,280 --> 00:42:39,600 THIS IS A MUCH BROADER PHENOMENA 1267 00:42:39,600 --> 00:42:40,760 THAT MIGHT HAVE BEEN INDICATED 1268 00:42:40,760 --> 00:42:43,240 BY MY ONE INTRODUCTORY STUDY OF 1269 00:42:43,240 --> 00:42:45,800 THE LAK FAIDGES. 1270 00:42:45,800 --> 00:42:46,480 PHAGES. 1271 00:42:46,480 --> 00:42:47,440 WHAT'S EVEN MORE INTERESTING, I 1272 00:42:47,440 --> 00:42:50,520 THINK, IS THIS RESULT 1273 00:42:50,520 --> 00:42:52,240 ILLUSTRATED HERE WHERE WE HAVE 1274 00:42:52,240 --> 00:42:54,880 CLOSELY RELATED PHAGES, CLOSE 1275 00:42:54,880 --> 00:42:56,200 TOGETHER ON THE TREE THAT HAVE 1276 00:42:56,200 --> 00:42:57,640 YELLOW, GREEN AND GREY CODE. 1277 00:42:57,640 --> 00:43:02,920 THAT MEANS STANDARD CODE, TAG 1278 00:43:02,920 --> 00:43:04,120 RE-ASSIGNED -- THEY CAN BE 1279 00:43:04,120 --> 00:43:05,640 CLOSELY, CLOSELY RELATED AND USE 1280 00:43:05,640 --> 00:43:06,640 DIFFERENT GENETIC CODES. 1281 00:43:06,640 --> 00:43:07,960 THIS IS NOT SOMETHING WE 1282 00:43:07,960 --> 00:43:08,800 EXPECTED AS ANOTHER EXAMPLE 1283 00:43:08,800 --> 00:43:13,080 HERE. 1284 00:43:13,080 --> 00:43:16,200 SO OVERALL, BETWEEN 2 AND 6% OF 1285 00:43:16,200 --> 00:43:18,040 THE PHAGES WE FOUND IN HUMAN 1286 00:43:18,040 --> 00:43:19,600 MICROBIOME USE AN ALTERNATE 1287 00:43:19,600 --> 00:43:19,920 GENETIC CODE. 1288 00:43:19,920 --> 00:43:21,240 SO IT'S NOT REALLY, REALLY 1289 00:43:21,240 --> 00:43:22,560 COMMON, BUT IT'S CERTAINLY NOT 1290 00:43:22,560 --> 00:43:25,240 RARE AND PROBABLY STILL 1291 00:43:25,240 --> 00:43:28,400 UNDERRECOGNIZED. 1292 00:43:28,400 --> 00:43:30,040 SO EXPANDING ON THIS JUST A TINY 1293 00:43:30,040 --> 00:43:35,760 BIT MORE, THE DIFFERENT CLAVES 1294 00:43:35,760 --> 00:43:38,600 ARE ILLUSTRATED BY THE ROWS, THE 1295 00:43:38,600 --> 00:43:40,040 BLOCKS, VERY CLOSELY RELATED 1296 00:43:40,040 --> 00:43:41,480 PHAGES CAN USE DIFFERENT GENETIC 1297 00:43:41,480 --> 00:43:45,840 CODES. 1298 00:43:45,840 --> 00:43:47,360 THIS IS AN EXAMPLE WHERE WE'VE 1299 00:43:47,360 --> 00:43:48,800 DONE WHOLE GENOME ALIGNMENTS, 1300 00:43:48,800 --> 00:43:50,120 WHICH YOU CAN ONLY DO WITH 1301 00:43:50,120 --> 00:43:51,560 CLOSELY RELATED GENOMES. 1302 00:43:51,560 --> 00:43:53,760 AND HERE IS 90% AVERAGE 1303 00:43:53,760 --> 00:43:55,240 NUCLEOTIDE IDENTITY. 1304 00:43:55,240 --> 00:43:57,640 AS WE CAN SEE HERE, THERE'S 1305 00:43:57,640 --> 00:44:00,360 INTERSPERSING OF TGA RECURRING 1306 00:44:00,360 --> 00:44:03,320 PHAGES, AND STANDARD CODE 1307 00:44:03,320 --> 00:44:03,680 PHAGES. 1308 00:44:03,680 --> 00:44:05,400 WHEN WE ALIGN THE GENOMES, YOU 1309 00:44:05,400 --> 00:44:06,960 CAN ALIGN THE WHOLE GENOMES HERE 1310 00:44:06,960 --> 00:44:08,760 AS SHOWN BELOW, WE FIND AGAIN 1311 00:44:08,760 --> 00:44:10,040 IT'S STRUCTURAL AND ACTUALLY 1312 00:44:10,040 --> 00:44:12,400 LYSIS PROTEINS THAT HAVE 1313 00:44:12,400 --> 00:44:13,680 ACCUMULATED THESE IN-FRAME STOP 1314 00:44:13,680 --> 00:44:15,880 CODONS OR WHAT WOULD BE STOP 1315 00:44:15,880 --> 00:44:16,840 CODONS IF READ IN THE NORMAL 1316 00:44:16,840 --> 00:44:18,440 WAY, AND WHAT'S PERHAPS EVEN 1317 00:44:18,440 --> 00:44:20,640 MORE INTERESTING IS THAT THE 1318 00:44:20,640 --> 00:44:23,240 STOP CODON THAT'S BEEN 1319 00:44:23,240 --> 00:44:24,680 RE-ASSIGNED HERE IS ALMOST NOT 1320 00:44:24,680 --> 00:44:27,080 USED IN THE STANDARD CODE PHAGE. 1321 00:44:27,080 --> 00:44:30,400 SO IT WOULD APPEAR THAT A 1322 00:44:30,400 --> 00:44:33,280 PRECURSOR, AND THIS IS MORE 1323 00:44:33,280 --> 00:44:34,920 GENERALLY TRUE, BY THE WAY, 1324 00:44:34,920 --> 00:44:35,920 PRECURSOR CODE SWITCH IS 1325 00:44:35,920 --> 00:44:38,640 PROBABLY REDUCTION IN USE OF THE 1326 00:44:38,640 --> 00:44:41,840 CODON THAT'S BEEN RE-ASSIGNED. 1327 00:44:41,840 --> 00:44:43,400 ANOTHER DRIVER APPEARS TO BE LOW 1328 00:44:43,400 --> 00:44:46,640 GC. 1329 00:44:46,640 --> 00:44:48,680 SO LOW GC, STOP CODON AVOIDANCE, 1330 00:44:48,680 --> 00:44:50,280 AND THE CODE CAN SWITCH. 1331 00:44:50,280 --> 00:44:53,040 SO THIS TELLS US THE GENETIC 1332 00:44:53,040 --> 00:44:59,960 CODE IS EVOLUTION MORE DYNE 1333 00:44:59,960 --> 00:45:00,280 EXPECTED. 1334 00:45:00,280 --> 00:45:01,880 WE THINK THE RE-ASSIGNMENT OF 1335 00:45:01,880 --> 00:45:02,880 STOP CODONS MAY BE IMPORTANT IN 1336 00:45:02,880 --> 00:45:03,960 TERMS OF THE PROCESS OF 1337 00:45:03,960 --> 00:45:05,320 INFECTION AND SUCCESSFUL 1338 00:45:05,320 --> 00:45:07,120 INFECTION BY THE PHAGES FOR THE 1339 00:45:07,120 --> 00:45:07,840 FOLLOWING REASONS. 1340 00:45:07,840 --> 00:45:10,720 WE SEE THAT MANY OF THE PHAGES 1341 00:45:10,720 --> 00:45:11,760 ENCODE SOME MACHINERY KNOWN TO 1342 00:45:11,760 --> 00:45:14,960 BE REQUIRED FOR CODE SWITCH. 1343 00:45:14,960 --> 00:45:17,400 THESE REQUIRE -- THIS INVOLVES A 1344 00:45:17,400 --> 00:45:18,960 TRNA THAT CAN RECOGNIZE THE STOP 1345 00:45:18,960 --> 00:45:19,360 CODON. 1346 00:45:19,360 --> 00:45:27,000 IN SOME CASES, WE CAN IDENTIFY A 1347 00:45:27,000 --> 00:45:27,880 SYNTHETASE AND THAT WOULD 1348 00:45:27,880 --> 00:45:28,840 RECOGNIZE STOP CODONS. 1349 00:45:28,840 --> 00:45:31,240 WE THINK DURING THE EARLY PART 1350 00:45:31,240 --> 00:45:33,400 OF INFECTION, THE GENOME IS READ 1351 00:45:33,400 --> 00:45:35,160 WITH CODE 11, THE HOST'S 1352 00:45:35,160 --> 00:45:36,760 BACTERIAL CODE. 1353 00:45:36,760 --> 00:45:39,360 AND THEN THE PHAGE MANAGES TO 1354 00:45:39,360 --> 00:45:40,720 PRODUCE THIS CODE SWITCH 1355 00:45:40,720 --> 00:45:41,960 MACHINERY, AND NOW IT FLIPS THE 1356 00:45:41,960 --> 00:45:43,240 RIBOSOME. 1357 00:45:43,240 --> 00:45:45,240 SO THAT IT READS THE STOP CODON 1358 00:45:45,240 --> 00:45:48,320 AS THE AMINO ACID OF CHOICE. 1359 00:45:48,320 --> 00:45:50,800 AND WE THINK THAT THIS IS A 1360 00:45:50,800 --> 00:45:52,200 SPECULATION, WE NEED TO DO 1361 00:45:52,200 --> 00:45:53,600 EXPERIMENTS TO VALIDATE THIS, 1362 00:45:53,600 --> 00:45:55,480 THAT POSSIBLY THIS IS BECAUSE 1363 00:45:55,480 --> 00:45:58,400 IT'S REALLY IMPORTANT THAT THE 1364 00:45:58,400 --> 00:45:59,960 PHAGE NOT PREMATURELY PRODUCE 1365 00:45:59,960 --> 00:46:01,840 THE PROTEINS INVOLVED IN LYSIS 1366 00:46:01,840 --> 00:46:03,040 AND STRUCTURAL PROTEINS. 1367 00:46:03,040 --> 00:46:05,240 SO IT MAY JUST BE AN INSURANCE 1368 00:46:05,240 --> 00:46:10,280 POLICY FOR THAT REASON. 1369 00:46:10,280 --> 00:46:13,280 I WANT TO SAY THE ALTERNATE 1370 00:46:13,280 --> 00:46:16,560 CODED PHAGES -- WE'VE BEEN ABLE 1371 00:46:16,560 --> 00:46:18,120 TO IDENTIFY INCORPORATED INTO 1372 00:46:18,120 --> 00:46:21,400 THE GENOME, IN OTHER WORDS, PRO 1373 00:46:21,400 --> 00:46:23,000 PHAGE, THAT USE THE ALTERNATE 1374 00:46:23,000 --> 00:46:23,600 GENETIC CODE. 1375 00:46:23,600 --> 00:46:25,280 SO THIS IS JUST TWO EXAMPLES, 1376 00:46:25,280 --> 00:46:27,840 ONE IN THE PREVOTELLA GENOME, 1377 00:46:27,840 --> 00:46:30,520 QUITE SMALL PHAGES, AND LIKEWISE 1378 00:46:30,520 --> 00:46:32,400 IN A FIRMICUTE GENOME. 1379 00:46:32,400 --> 00:46:34,040 SO WE CAN PICK THIS OUT VERY 1380 00:46:34,040 --> 00:46:39,160 EASILY BECAUSE THE NORMAL TBEENE 1381 00:46:39,160 --> 00:46:42,040 PREDICTIONS GIVE YOU SUCH LOW 1382 00:46:42,040 --> 00:46:45,040 DENSITY. 1383 00:46:45,040 --> 00:46:47,560 SO THE LAST PIECE OF WORK IS NOT 1384 00:46:47,560 --> 00:46:48,320 PUBLISHED YET. 1385 00:46:48,320 --> 00:46:51,520 IT DONE WITH LONG TERM 1386 00:46:51,520 --> 00:46:53,080 COLLABORATORS WHO DO PROTEOMICS. 1387 00:46:53,080 --> 00:46:54,280 WE'VE PROVIDED THEM WITH HUMAN 1388 00:46:54,280 --> 00:46:56,280 MICROBIOME SAMPLES THAT CONTAIN 1389 00:46:56,280 --> 00:46:57,360 ABUNDANT ALTERNATIVELY CODED 1390 00:46:57,360 --> 00:47:00,000 PHAGES AND THEY'VE BEEN ABLE TO 1391 00:47:00,000 --> 00:47:01,040 CONFIRM THE BIOINFORMATIC 1392 00:47:01,040 --> 00:47:03,200 PREDICTION THAT THE STOP CODON 1393 00:47:03,200 --> 00:47:04,360 READS AS, IN THIS CASE, 1394 00:47:04,360 --> 00:47:05,440 GLUTAMINE. 1395 00:47:05,440 --> 00:47:10,440 THIS WAS ACTUALLY -- WHEN WE SAW 1396 00:47:10,440 --> 00:47:14,560 THE LAK FAIDGES BECAUSE E 1397 00:47:14,560 --> 00:47:16,880 LISTING OF ALL GENETIC CODES 1398 00:47:16,880 --> 00:47:19,960 THAT EXIST IN BIOLOGY, TOOK US A 1399 00:47:19,960 --> 00:47:23,040 WHILE TO REALIZE IT GOES 11, 12, 1400 00:47:23,040 --> 00:47:23,680 13, 14, 16. 1401 00:47:23,680 --> 00:47:24,760 SO THERE IS A CODE 15. 1402 00:47:24,760 --> 00:47:26,360 WHEN I CONTACTED NIH AND I SAID, 1403 00:47:26,360 --> 00:47:28,800 HEY, BY THE WAY, THERE IS A CODE 1404 00:47:28,800 --> 00:47:30,120 15, THEY TELL ME IT'S NEVER BEEN 1405 00:47:30,120 --> 00:47:31,640 SEEN IN BIOLOGY, BUT HOPEFULLY 1406 00:47:31,640 --> 00:47:33,600 NOW WE HAVE PROTEOMIC 1407 00:47:33,600 --> 00:47:34,920 VERIFICATION NOT JUST BIOIB FOR 1408 00:47:34,920 --> 00:47:37,240 MA 1409 00:47:37,240 --> 00:47:38,040 BIOINFORMATICS, WE CAN FIX THE 1410 00:47:38,040 --> 00:47:38,280 LISTING. 1411 00:47:38,280 --> 00:47:40,600 SO I TELL YOU, CODE 15 REALLY 1412 00:47:40,600 --> 00:47:42,040 DOES EXIST, I THINK VERY CLEARLY 1413 00:47:42,040 --> 00:47:43,840 NOW, AND THIS IS JUST A DIAGRAM 1414 00:47:43,840 --> 00:47:46,200 OF THE TWO PHAGES THAT WERE 1415 00:47:46,200 --> 00:47:48,280 STUDIED WITH THE ASTERISKS 1416 00:47:48,280 --> 00:47:49,600 INDICATING WHERE THERE WAS 1417 00:47:49,600 --> 00:47:52,760 PROTEOMIC CONFIRMATION THAT TAG 1418 00:47:52,760 --> 00:47:57,120 EQUALS GLUTAMINE. 1419 00:47:57,120 --> 00:47:58,320 SO I THINK IT'S A GOOD TIME TO 1420 00:47:58,320 --> 00:47:59,480 WRAP UP, GIVEN THE HOUR. 1421 00:47:59,480 --> 00:48:00,880 I WANTED TO MAKE A FEW 1422 00:48:00,880 --> 00:48:06,360 CONCLUSIONS. 1423 00:48:06,360 --> 00:48:07,560 I FIRST WANT TO BACK OUT AND SAY 1424 00:48:07,560 --> 00:48:09,960 AGAIN THERE'S A LOT IN THE HUMAN 1425 00:48:09,960 --> 00:48:12,440 MICROBIOME THAT WOULD BE MISSED 1426 00:48:12,440 --> 00:48:13,240 BY CULTURE INDEPENDENT 1427 00:48:13,240 --> 00:48:14,440 APPROACHES AND THE ENVIRONMENT 1428 00:48:14,440 --> 00:48:17,400 MORE BROADLY, OF COURSE, AS 1429 00:48:17,400 --> 00:48:18,080 WELL. 1430 00:48:18,080 --> 00:48:19,960 THEY'RE NOW KNOWN TO SOME EXTENT 1431 00:48:19,960 --> 00:48:21,480 THROUGH GENOME RESOLVED META 1432 00:48:21,480 --> 00:48:22,080 GENOMICS. 1433 00:48:22,080 --> 00:48:23,480 THERE'S A LOT WE CAN PREDICT, A 1434 00:48:23,480 --> 00:48:26,080 LOT WE STILL DON'T KNOW. 1435 00:48:26,080 --> 00:48:28,560 MANY OF THESE ORGANISMS MAY HAVE 1436 00:48:28,560 --> 00:48:30,240 MEDICAL SIGNIFICANCE. 1437 00:48:30,240 --> 00:48:32,040 AND THE EVIDENCE IS EMERGING 1438 00:48:32,040 --> 00:48:33,240 FROM THE STUDIES OF OTHERS THAT 1439 00:48:33,240 --> 00:48:34,560 THEY DO. 1440 00:48:34,560 --> 00:48:36,360 AS I SAID, WE'RE INTERESTED IN 1441 00:48:36,360 --> 00:48:37,760 WHERE DO THEY COME FROM, HOW 1442 00:48:37,760 --> 00:48:39,960 DOES THE ENVIRONMENT IMPACT 1443 00:48:39,960 --> 00:48:41,840 HUMAN MICROBIOME DEVELOPMENT. 1444 00:48:41,840 --> 00:48:44,280 WE THINK THAT THEY, GIVEN THE 1445 00:48:44,280 --> 00:48:45,760 LATE APPEARANCE OF HUMANS, MUST 1446 00:48:45,760 --> 00:48:46,840 HAVE COME FROM THE ENVIRONMENT 1447 00:48:46,840 --> 00:48:50,800 AND PROBABLY THEY CAME FROM 1448 00:48:50,800 --> 00:48:51,080 GROUNDWATER. 1449 00:48:51,080 --> 00:48:54,040 COLONIZATION WAS PROBS BLI PROBY 1450 00:48:54,040 --> 00:48:54,840 ACCIDENTAL FIRST BUT OVER TIME, 1451 00:48:54,840 --> 00:48:55,680 IN EVOLUTION OF THE ASSOCIATION, 1452 00:48:55,680 --> 00:49:00,960 THERE WERE CHANGES IN THE JEAN E 1453 00:49:00,960 --> 00:49:01,720 REPERTOIRES MOSTLY ASSOCIATED 1454 00:49:01,720 --> 00:49:02,880 WITH LOSS OF CAPACITIES AND 1455 00:49:02,880 --> 00:49:03,480 GENOME REDUCTION. 1456 00:49:03,480 --> 00:49:04,960 I THINK IT'S REALLY IMPORTANT WE 1457 00:49:04,960 --> 00:49:07,720 KEEP OUR EYES ON NOT JUST THE 1458 00:49:07,720 --> 00:49:11,880 MICROBES BUT THEIR ASSOCIATED 1459 00:49:11,880 --> 00:49:13,240 BACTERIOPHAGES OR VIRUSES. 1460 00:49:13,240 --> 00:49:16,800 WE SEE CLOSELY RELATED PHAGES IN 1461 00:49:16,800 --> 00:49:19,600 NOT VERY CLOSELY RELATED 1462 00:49:19,600 --> 00:49:22,600 ORGANISMS, AND WE SEE NOT SO 1463 00:49:22,600 --> 00:49:25,320 CLOSELY RELATED PHAGES IN 1464 00:49:25,320 --> 00:49:26,400 CLOSELY RELATE ORGANISMS. 1465 00:49:26,400 --> 00:49:28,440 FOR EXAMPLE, HUMANS AND BABOONS, 1466 00:49:28,440 --> 00:49:30,080 THEIR PHAGES ARE VERY DIFFERENT. 1467 00:49:30,080 --> 00:49:31,200 HUMANS, DOGS AND HORSES, THEY 1468 00:49:31,200 --> 00:49:34,840 SEEM TO BE MUMP CLOSER. 1469 00:49:34,840 --> 00:49:35,720 MUCH CLOSER. 1470 00:49:35,720 --> 00:49:38,480 SO ASSOCIATION MAY BE IMPORTANT 1471 00:49:38,480 --> 00:49:41,560 IN TERMS OF -- INTO THE HUMAN 1472 00:49:41,560 --> 00:49:42,520 MICROBIOME. 1473 00:49:42,520 --> 00:49:43,840 I PERSONALLY FIND THAT THIS 1474 00:49:43,840 --> 00:49:47,320 TOPIC OF ALTERNATE CODING OF 1475 00:49:47,320 --> 00:49:48,400 PHAGES IS REALLY FASCINATING. 1476 00:49:48,400 --> 00:49:49,920 I CAN'T TELL YOU WHY IT'S GOING 1477 00:49:49,920 --> 00:49:51,840 TO BE IMPORTANT YET, BUT I KNOW 1478 00:49:51,840 --> 00:49:53,240 ACTUALLY THE PERSON I SAT NEXT 1479 00:49:53,240 --> 00:49:55,960 TO ON THE PLANE COMING OUT HERE 1480 00:49:55,960 --> 00:49:58,440 RUNS A NON-PROFIT IN OAKLAND ON 1481 00:49:58,440 --> 00:49:59,680 PHAGE THERAPY, AND SHE WAS GOING 1482 00:49:59,680 --> 00:50:00,680 TO A CONFERENCE WHERE SHE'S 1483 00:50:00,680 --> 00:50:04,160 GOING TO CONVENE A SECTION ON 1484 00:50:04,160 --> 00:50:05,120 SUCCESSFUL IMPLEMENTATION OF 1485 00:50:05,120 --> 00:50:06,240 PHAGE THERAPY TRIALS AND SO 1486 00:50:06,240 --> 00:50:07,560 FORTH, AND I THINK THAT THERE 1487 00:50:07,560 --> 00:50:09,800 MAY BE SOME REASON TO LOOK AT 1488 00:50:09,800 --> 00:50:10,840 THE GENETIC CODE AND HOW IT CAN 1489 00:50:10,840 --> 00:50:13,360 BE USED BY PHAGES TO JUST ADD 1490 00:50:13,360 --> 00:50:17,360 THAT LITTLE BIT MORE PROBABILITY 1491 00:50:17,360 --> 00:50:19,880 OF SUCCESSFUL INFECTION. 1492 00:50:19,880 --> 00:50:22,760 PERHAPS MORE BROADLY 1493 00:50:22,760 --> 00:50:25,040 EVOLUTIONARY SPEAKING, I THINK A 1494 00:50:25,040 --> 00:50:29,040 REALLY FASCINATING -- THE IDEA 1495 00:50:29,040 --> 00:50:30,240 THAT A PHAGE CAN SWITCH THEIR 1496 00:50:30,240 --> 00:50:32,960 CODE VERY EASILY. 1497 00:50:32,960 --> 00:50:34,160 THEIR CODE SWITCH IS VERY 1498 00:50:34,160 --> 00:50:34,640 FACILE. 1499 00:50:34,640 --> 00:50:36,640 IT'S NOT FIXED, IT'S NOT STATIC. 1500 00:50:36,640 --> 00:50:37,800 PROBABLY IT CAN SWITCH ONE WAY 1501 00:50:37,800 --> 00:50:40,560 AND PROBABLY BACK AGAIN. 1502 00:50:40,560 --> 00:50:43,240 THERE ARE OBVIOUS COMPONENTS OF 1503 00:50:43,240 --> 00:50:45,240 THE MECHANISM OF CODE 1504 00:50:45,240 --> 00:50:46,440 ADAPTATION, BUT I'M SURE THERE 1505 00:50:46,440 --> 00:50:47,920 WILL BE A LOT MORE TO LEARN AS 1506 00:50:47,920 --> 00:50:50,760 WE START TO GET ALTERNATE PHAGES 1507 00:50:50,760 --> 00:50:52,200 INTO CULTURE, SO WHY HAVE WE NOT 1508 00:50:52,200 --> 00:50:53,400 DONE THE EXPERIMENTS ALREADY? 1509 00:50:53,400 --> 00:50:56,920 THERE IS, TO MY KNOWLEDGE, NO 1510 00:50:56,920 --> 00:50:58,240 ALTERNATIVELY CODED PHAGE IN 1511 00:50:58,240 --> 00:50:59,560 CULTURE, AT LEAST NOT ONE 1512 00:50:59,560 --> 00:51:05,720 PUBLISHED TO THIS DAY. 1513 00:51:05,720 --> 00:51:07,280 I WANT TO THANK OBVIOUSLY OUR 1514 00:51:07,280 --> 00:51:09,560 FUNDING SOURCES WHICH INCLUDE 1515 00:51:09,560 --> 00:51:10,080 THE NATIONAL INSTITUTES OF 1516 00:51:10,080 --> 00:51:11,240 HEALTH AND SOME OTHER 1517 00:51:11,240 --> 00:51:12,240 ORGANIZATIONS. 1518 00:51:12,240 --> 00:51:14,560 I LISTED PUBLICATIONS 1519 00:51:14,560 --> 00:51:15,840 THROUGHOUT, BUT THE PEOPLE WHOSE 1520 00:51:15,840 --> 00:51:17,720 NAMES HERE ARE, WITH ONE 1521 00:51:17,720 --> 00:51:21,240 EXCEPTION, JOANNE SANTINI AT THE 1522 00:51:21,240 --> 00:51:22,360 TOP ARE MEMBERS OR PAST MEMBERS 1523 00:51:22,360 --> 00:51:24,080 OF MY LAB AND WE'VE BEEN REALLY 1524 00:51:24,080 --> 00:51:25,400 LUCKY TO WORK WITH MEMBERS OF 1525 00:51:25,400 --> 00:51:31,760 THE FORSYTHE INSTITUTE ON THE 1526 00:51:31,760 --> 00:51:32,240 TH7 SACCHARIBACTERIA. 1527 00:51:32,240 --> 00:51:33,160 I'D BE HAPPY TO TAKE QUESTIONS. 1528 00:51:33,160 --> 00:51:37,080 [APPLAUSE] 1529 00:51:37,080 --> 00:51:40,760 >>I'M GOING TO START FROM ONE ONLINE 1530 00:51:40,760 --> 00:51:47,120 THE APPEARANCE OF A GROUP OF 1531 00:51:47,120 --> 00:51:49,520 SYMBIONTS THAT HAVE LOST AEROBIC 1532 00:51:49,520 --> 00:51:50,720 METABOLISM RAISE THIS QUESTION: 1533 00:51:50,720 --> 00:51:54,360 I HAVE ALWAYS THOUGHT THAT THE 1534 00:51:54,360 --> 00:51:56,400 ORIGINAL MITOCHONDRION WAS 1535 00:51:56,400 --> 00:51:59,760 ENGULFED WHEN IT CONTAINED ALL 1536 00:51:59,760 --> 00:52:00,160 OXFOS CAPABILITY. 1537 00:52:00,160 --> 00:52:01,560 DO YOU SEE EVIDENCE THAT THOSE 1538 00:52:01,560 --> 00:52:03,360 ORIGINAL ORGANISMS, 1539 00:52:03,360 --> 00:52:05,520 QUOTE-UNQUOTE, MAY HAVE ALREADY 1540 00:52:05,520 --> 00:52:09,600 LOST MOST ETC PROTEINS, IE, ARE 1541 00:52:09,600 --> 00:52:12,640 THERE NASCENT NEW MITOCHONDRIA 1542 00:52:12,640 --> 00:52:13,840 OUT THERE AS SYMBIONTS? 1543 00:52:13,840 --> 00:52:15,360 >>OH, I LOVE THIS QUESTION. 1544 00:52:15,360 --> 00:52:19,960 BUT FIRST OF ALL, IT'S A BIT 1545 00:52:19,960 --> 00:52:21,600 BACKWARDS. 1546 00:52:21,600 --> 00:52:22,640 TRANSPORT CHAIN -- THEY GO 1547 00:52:22,640 --> 00:52:23,600 TOGETHER, I THINK IT'S ACTUALLY 1548 00:52:23,600 --> 00:52:24,200 THE OPPOSITE. 1549 00:52:24,200 --> 00:52:31,280 I THINK THAT THE ORGANISMS IN 1550 00:52:31,280 --> 00:52:32,880 SOIL PROBABLY GAINED THE 1551 00:52:32,880 --> 00:52:33,640 POSSIBILITY -- IT'S NOT THAT 1552 00:52:33,640 --> 00:52:37,840 WELL REPRESENTED AT THIS TIME. 1553 00:52:37,840 --> 00:52:39,520 AND MOSTLY THEY'RE ASSOCIATED 1554 00:52:39,520 --> 00:52:39,800 ORGANISMS. 1555 00:52:39,800 --> 00:52:41,640 I THINK THE VAST MAJORITY OF 1556 00:52:41,640 --> 00:52:46,040 THESE CPR ORGANISMS ARE AN 1557 00:52:46,040 --> 00:52:47,400 AEROBES AND THAT SEEMS TO BE THE 1558 00:52:47,400 --> 00:52:48,800 NORMAL MODE OF LIFE IN EARTH'S 1559 00:52:48,800 --> 00:52:51,680 ENVIRONMENTS WHERE THEY OCCUR. 1560 00:52:51,680 --> 00:52:52,800 AND IN THE HUMAN BODY. 1561 00:52:52,800 --> 00:52:55,520 SO I DON'T KNOW ABOUT THE -- I 1562 00:52:55,520 --> 00:52:58,240 DON'T THINK THE ANALOGY WITH 1563 00:52:58,240 --> 00:52:59,040 MITOCHONDRIA IS QUITE 1564 00:52:59,040 --> 00:52:59,920 APPROPRIATE IN THIS KAY. 1565 00:52:59,920 --> 00:53:01,360 I THINK IT'S MORE LIKE ANOTHER 1566 00:53:01,360 --> 00:53:03,520 KIND OF ORGANISM, ORGANISM 1567 00:53:03,520 --> 00:53:06,120 ASSOCIATION, SO ON THE CONTINUUM 1568 00:53:06,120 --> 00:53:09,160 OF ENDOSYMBIOSIS WHICH WOULD BE 1569 00:53:09,160 --> 00:53:10,600 THE MITOCHONDRION AND LOOSE 1570 00:53:10,600 --> 00:53:11,480 ASSOCIATION -- THIS IS A CASE 1571 00:53:11,480 --> 00:53:14,480 WHERE THEY HAVE DIRECT PHYSICAL 1572 00:53:14,480 --> 00:53:17,600 CONTACT OR EPISIM SYMBIOSIS. 1573 00:53:17,600 --> 00:53:18,840 I THINK THAT'S AN EVOLVED 1574 00:53:18,840 --> 00:53:20,600 STRATEGY, I THINK IT'S A VERY 1575 00:53:20,600 --> 00:53:22,000 COMMON STRATEGY AND I THINK IT'S 1576 00:53:22,000 --> 00:53:23,560 EXTREMELY UNDERSTUDIED, BUT I 1577 00:53:23,560 --> 00:53:26,160 DON'T THINK IT'S ANALOGOUS IN 1578 00:53:26,160 --> 00:53:26,800 QUITE THAT WAY. 1579 00:53:26,800 --> 00:53:27,720 >> HI. 1580 00:53:27,720 --> 00:53:29,400 THANK YOU FOR THE LECTURE. 1581 00:53:29,400 --> 00:53:34,200 MY QUESTION IS ABOUT LAK PHAGES, 1582 00:53:34,200 --> 00:53:35,760 BECAUSE YOU SAID THAT THEY CAN 1583 00:53:35,760 --> 00:53:37,560 BE REALLY VARIABLE IN THE GENOME 1584 00:53:37,560 --> 00:53:41,240 SIZE, BUT IT ALSO MEANS THAT 1585 00:53:41,240 --> 00:53:44,760 THEY HAVE TO BE ABLE TO PAD THIS 1586 00:53:44,760 --> 00:53:46,200 GENOME IN THE CA PSI. 1587 00:53:46,200 --> 00:53:47,600 AS YOU SHOWED ON ONE OF THE 1588 00:53:47,600 --> 00:53:50,240 TREE, SOME OF THEM REALLY -- 1589 00:53:50,240 --> 00:53:52,600 LIKE SOME GROUPS REALLY WERE IN 1590 00:53:52,600 --> 00:53:53,760 THE GENOME SIZE AS OTHERS ARE 1591 00:53:53,760 --> 00:53:54,280 NOT. 1592 00:53:54,280 --> 00:53:56,360 DO YOU SEE ANY DIFFERENCE IN THE 1593 00:53:56,360 --> 00:53:58,160 CAPSIDS OR PROTEIN THAT FORM 1594 00:53:58,160 --> 00:53:59,960 THOSE CAPSIDS? 1595 00:53:59,960 --> 00:54:01,320 >> I THINK BY WAY OF 1596 00:54:01,320 --> 00:54:02,920 CLARIFICATION I WANT TO SAY I 1597 00:54:02,920 --> 00:54:04,040 TALKED ABOUT TWO THINGS, I 1598 00:54:04,040 --> 00:54:05,840 TALKED ABOUT LAK PHAGES FIRST 1599 00:54:05,840 --> 00:54:08,800 AND THEIR GENOME SIZES RANGE 1600 00:54:08,800 --> 00:54:09,880 FROM 465KB TO 660. 1601 00:54:09,880 --> 00:54:11,160 SO IT'S NOT A HUGE RANGE IN 1602 00:54:11,160 --> 00:54:12,280 SIZE. 1603 00:54:12,280 --> 00:54:13,560 BUT IT'S LINEAGE-SPECIFIC. 1604 00:54:13,560 --> 00:54:15,520 SO THERE'S A FEW MAJOR LINEAGES 1605 00:54:15,520 --> 00:54:16,360 OF LAK PHAGES. 1606 00:54:16,360 --> 00:54:17,480 SO I THINK THERE'S NO BIG 1607 00:54:17,480 --> 00:54:19,200 MYSTERY WITH THE CAPSIDS. 1608 00:54:19,200 --> 00:54:22,880 WE CAN IDENTIFY THE CAPSID 1609 00:54:22,880 --> 00:54:24,880 PROTEINS, BUT SO THEY'VE EVOLVED 1610 00:54:24,880 --> 00:54:26,560 DIFFERENT SIZES BUT THE SIZES 1611 00:54:26,560 --> 00:54:27,760 AREN'T HUGELY DIFFERENT AND 1612 00:54:27,760 --> 00:54:28,840 CLOSELY RELATED LAK PHAGES HAVE 1613 00:54:28,840 --> 00:54:29,720 THE SAME SIZE. 1614 00:54:29,720 --> 00:54:31,240 WHAT I SHOWED YOU IN TERMS OF 1615 00:54:31,240 --> 00:54:33,520 THE HUGE RANGE IN GENOME SIZE, 1616 00:54:33,520 --> 00:54:34,280 THEY'RE ALL-OF-US TERNTIVELY 1617 00:54:34,280 --> 00:54:35,480 CODED PHAGES. 1618 00:54:35,480 --> 00:54:37,200 IN THAT CASE, THEY'VE GOT 1619 00:54:37,200 --> 00:54:37,840 DIFFERENT HOSTS, DIFFERENT TYPES 1620 00:54:37,840 --> 00:54:38,400 OF PHAGES. 1621 00:54:38,400 --> 00:54:40,480 THEY'RE JUST ALL OVER THE TREE. 1622 00:54:40,480 --> 00:54:42,680 AND SO I'M SURE THERE PROBABLY 1623 00:54:42,680 --> 00:54:44,160 WOULD BE DIFFERENCES IN THE 1624 00:54:44,160 --> 00:54:45,040 CAPSID PROTEINS BUT I HAVEN'T 1625 00:54:45,040 --> 00:54:46,240 LOOKED AT THAT IN DETAIL. 1626 00:54:46,240 --> 00:54:48,240 >> BUT I MEAN, YOU HAVE SOME 1627 00:54:48,240 --> 00:54:50,240 CLOSELY RELATED GROUPS THAT VARY 1628 00:54:50,240 --> 00:54:52,960 IN SIZE, YES, FOR ALTERNATIVE -- 1629 00:54:52,960 --> 00:54:53,960 THE ONE WITH ALTERNATIVE. 1630 00:54:53,960 --> 00:54:56,160 SO FOR THE CLOSELY RELATED 1631 00:54:56,160 --> 00:54:57,520 GROUP, HOW YOU EXPLAINED THAT 1632 00:54:57,520 --> 00:54:58,400 THEY CAN TACK THESE GENES -- 1633 00:54:58,400 --> 00:54:59,680 >> I SEE WHERE YOU'RE GOING WITH 1634 00:54:59,680 --> 00:55:00,160 THIS. 1635 00:55:00,160 --> 00:55:01,800 SO THAT'S A PRETTY ZOOMED OUT 1636 00:55:01,800 --> 00:55:03,280 VIEW OF THE TREE, AND I DON'T 1637 00:55:03,280 --> 00:55:06,200 KNOW HOW REALLY VERY CLOSELY 1638 00:55:06,200 --> 00:55:07,400 RELATED THEY ARE, BUT YES, IT 1639 00:55:07,400 --> 00:55:08,880 TENDS TO BE, AND I'M PRETTY SURE 1640 00:55:08,880 --> 00:55:10,640 ABOUT THIS, THAT CLOSELY RELATED 1641 00:55:10,640 --> 00:55:12,120 PHAGES HAVE THE SAME GINO SIZE. 1642 00:55:12,120 --> 00:55:14,440 SO IF WE FIND ONE LARGE PHAGE, 1643 00:55:14,440 --> 00:55:19,000 WE FIND A CLAVE OF THEM. 1644 00:55:19,000 --> 00:55:20,520 CLADES OF HUGE PHAGE ACROSS 1645 00:55:20,520 --> 00:55:22,920 THOSE ENVIRONMENTS. 1646 00:55:22,920 --> 00:55:24,920 SO ONE, YOU FIND MORE BIG. 1647 00:55:24,920 --> 00:55:27,040 AND MORE DISAT THAT PARTICULAR 1648 00:55:27,040 --> 00:55:27,640 TIMELY BRANCHING, WE FIND THE 1649 00:55:27,640 --> 00:55:28,360 SMALLER ONES. 1650 00:55:28,360 --> 00:55:29,800 SO I DON'T KNOW ANYTHING BEYOND 1651 00:55:29,800 --> 00:55:31,040 THAT IN TERMS OF THE MECHANISM, 1652 00:55:31,040 --> 00:55:34,200 BUT I THINK IT'S QUITE A BIT OF 1653 00:55:34,200 --> 00:55:34,920 EVOLUTIONARY TIME THAT SEPARATES 1654 00:55:34,920 --> 00:55:35,520 THEM. 1655 00:55:35,520 --> 00:55:36,800 >> THANK YOU. 1656 00:55:36,800 --> 00:55:41,720 >> ANY OTHER QUESTIONS? 1657 00:55:41,720 --> 00:55:48,000 SUSAN, GO AHEAD. 1658 00:55:48,000 --> 00:55:49,600 >> LET ME START WITH ONE BACK 1659 00:55:49,600 --> 00:55:52,280 WHEN YOU WERE SHOWING THE 1660 00:55:52,280 --> 00:55:56,440 ACQUISITION OR LOSS OF METABOLIC 1661 00:55:56,440 --> 00:55:58,920 THINGS AND SORT OF INDEPENDENT 1662 00:55:58,920 --> 00:55:59,160 EVENTS. 1663 00:55:59,160 --> 00:56:01,200 IT LOOKED LIKE THEY WERE IN 1664 00:56:01,200 --> 00:56:05,360 GROUPS AS IF THERE'S NOT A 1665 00:56:05,360 --> 00:56:06,520 CAPACITY THAT MUST BE GAINED 1666 00:56:06,520 --> 00:56:07,840 WHEN YOU GO FROM THE 1667 00:56:07,840 --> 00:56:09,000 ENVIRONMENT, THAT YOU CAN DO IT 1668 00:56:09,000 --> 00:56:10,360 MANY DIFFERENT WAYS AND IT'S 1669 00:56:10,360 --> 00:56:13,720 NOT -- YOU KNOW, THAT YOU MUST 1670 00:56:13,720 --> 00:56:14,480 GET SOMETHING IN PARTICULAR. 1671 00:56:14,480 --> 00:56:16,000 IS THAT ACCURATE? 1672 00:56:16,000 --> 00:56:17,640 >> I THINK THAT'S FAIR, YES. 1673 00:56:17,640 --> 00:56:20,440 AND THE FACT THAT -- I MEAN, 1674 00:56:20,440 --> 00:56:22,680 THESE ARE PHYLUM LEVEL VIEW, SO 1675 00:56:22,680 --> 00:56:25,920 IF WE SAY A BRANCH -- THOSE HAVE 1676 00:56:25,920 --> 00:56:27,160 REALLY DIFFERENT ORGANISMS, SO 1677 00:56:27,160 --> 00:56:28,640 DIFFERENT STARTING POINTS, AND I 1678 00:56:28,640 --> 00:56:32,680 DO THINK IT'S REALLY -- AS IT 1679 00:56:32,680 --> 00:56:34,360 SHOWED SO FAR, CONTINUOUS 1680 00:56:34,360 --> 00:56:35,960 MODIFICATION, NOT ONE 1681 00:56:35,960 --> 00:56:36,280 REQUISITE -- 1682 00:56:36,280 --> 00:56:37,440 >> THING THAT YOU START WITH, 1683 00:56:37,440 --> 00:56:37,640 YEAH. 1684 00:56:37,640 --> 00:56:38,880 >> IN THE CASE OF THE LAK 1685 00:56:38,880 --> 00:56:40,920 PHAGES, IT'S REALLY INTERESTING 1686 00:56:40,920 --> 00:56:42,480 THAT WHAT STANDS OUT IS THE 1687 00:56:42,480 --> 00:56:42,680 GAINS. 1688 00:56:42,680 --> 00:56:44,720 IN THE CASE OF THE MICROBES, 1689 00:56:44,720 --> 00:56:46,400 IT'S MORE THE LOSS, LOSS OF 1690 00:56:46,400 --> 00:56:47,200 DIVERSITY. 1691 00:56:47,200 --> 00:56:49,800 DIVERSITY OF CAPACITIES. 1692 00:56:49,800 --> 00:56:52,200 >> MAYBE WHY YOU CAN DO MORE 1693 00:56:52,200 --> 00:56:52,440 EASILY. 1694 00:56:52,440 --> 00:56:54,160 >> OR WHAT YOU DON'T NEED TO DO, 1695 00:56:54,160 --> 00:56:54,640 YOU SHOULD. 1696 00:56:54,640 --> 00:56:58,680 ONCE YOU GET TO THE HUMAN BO BO, 1697 00:56:58,680 --> 00:56:59,840 IT'S REALLY DIFFERENT THAN BEING 1698 00:56:59,840 --> 00:57:07,800 IN AN AN AN AQUIFER OR SEDI. 1699 00:57:07,800 --> 00:57:10,160 >> I JUST HAD A COMMENT, NOT A 1700 00:57:10,160 --> 00:57:10,880 QUESTION. 1701 00:57:10,880 --> 00:57:12,360 >> OKAY. 1702 00:57:12,360 --> 00:57:16,800 I REALLY LOVE THE ALTERNATE 1703 00:57:16,800 --> 00:57:17,600 TRANSLATION CODE. 1704 00:57:17,600 --> 00:57:19,680 THAT'S REALLY FASCINATING. 1705 00:57:19,680 --> 00:57:22,240 BUT OF COURSE IN THE MODEL IN 1706 00:57:22,240 --> 00:57:23,440 WHICH -- SO THE PHAGES ARE 1707 00:57:23,440 --> 00:57:26,640 CARRYING THE MACHINERY TO DO 1708 00:57:26,640 --> 00:57:26,840 THAT. 1709 00:57:26,840 --> 00:57:27,560 >> FOR THE MOST PART. 1710 00:57:27,560 --> 00:57:29,960 >> AND YOU THINK THOSE ARE SORT 1711 00:57:29,960 --> 00:57:31,160 OF EARLY GENES THAT ARE COMING 1712 00:57:31,160 --> 00:57:32,560 IN, BUT NOT ONLY ARE THEY GOING 1713 00:57:32,560 --> 00:57:35,560 TO AFFECT WHEN THE PHAGE CAN 1714 00:57:35,560 --> 00:57:37,120 MAKE THOSE LYTIC ONES BUT 1715 00:57:37,120 --> 00:57:38,040 THEY'RE GOING TO DO STRANGE 1716 00:57:38,040 --> 00:57:39,360 THINGS TO THE HOST TOO. 1717 00:57:39,360 --> 00:57:41,680 AND DO YOU SEE ANY -- I MEAN, I 1718 00:57:41,680 --> 00:57:42,760 GUESS YOU NEED ONE THAT DOESN'T 1719 00:57:42,760 --> 00:57:45,760 DO IT AND ONE THAT DOES TO KNOW 1720 00:57:45,760 --> 00:57:49,000 WHETHER THE HOST HAS ADAPTED AT 1721 00:57:49,000 --> 00:57:49,400 ALL. 1722 00:57:49,400 --> 00:57:51,080 >> I HAVE TWO HUGE QUESTIONS AND 1723 00:57:51,080 --> 00:57:51,960 THIS IS A REALLY INTERESTING 1724 00:57:51,960 --> 00:57:52,240 QUESTION. 1725 00:57:52,240 --> 00:57:54,280 I THINK THAT -- WELL, WE JUST 1726 00:57:54,280 --> 00:57:55,880 DON'T KNOW, ARE ALL THE 1727 00:57:55,880 --> 00:57:57,840 RIBOSOMES SWITCHED, IS IT JUST A 1728 00:57:57,840 --> 00:57:59,600 SUBSET S IT A COMPLETE SWITCH? 1729 00:57:59,600 --> 00:58:00,720 THERE'S A LOT OF QUESTIONS 1730 00:58:00,720 --> 00:58:01,040 THERE. 1731 00:58:01,040 --> 00:58:02,560 WHAT WE COULD LOOK FOR ARE 1732 00:58:02,560 --> 00:58:04,160 PEPTIDES THAT ARE TERMINATED AND 1733 00:58:04,160 --> 00:58:05,480 CLASSIFY THEM AS TERMINATED 1734 00:58:05,480 --> 00:58:07,920 PHAGE PROTEINS, AND TERMINATED 1735 00:58:07,920 --> 00:58:09,400 HOST PROTEINS. 1736 00:58:09,400 --> 00:58:13,120 BECAUSE ONCE WE HAVE THE GENOMES 1737 00:58:13,120 --> 00:58:13,760 CULTIVATION-INDEPENDENT, REALLY, 1738 00:58:13,760 --> 00:58:17,200 WE CAN PLEA PREDICT THE PROTN 1739 00:58:17,200 --> 00:58:18,320 SEQUENCES AND THE PEPTIDES AND 1740 00:58:18,320 --> 00:58:19,960 WE CAN VALIDATE THEM. 1741 00:58:19,960 --> 00:58:21,480 SO WE REALLY NEED TO ASK THAT 1742 00:58:21,480 --> 00:58:23,640 QUESTION, DO THEY MAKE THE 1743 00:58:23,640 --> 00:58:25,600 TERMINATED -- THE PREMATURELY 1744 00:58:25,600 --> 00:58:27,000 TERMINATED BACTERIAL PROTEINS, 1745 00:58:27,000 --> 00:58:28,120 AND THE ONE QUESTION I WOULD ASK 1746 00:58:28,120 --> 00:58:31,240 ON TOP OF THAT IS, DOES THE HOST 1747 00:58:31,240 --> 00:58:31,760 BACK 1748 00:58:31,760 --> 00:58:33,280 BACTERIA HAVE A WAY OF SWITCHING 1749 00:58:33,280 --> 00:58:37,080 THE RIBOSOME RIBOSOME BACK? 1750 00:58:37,080 --> 00:58:38,280 BASED ON THE OTHER THINGS WE 1751 00:58:38,280 --> 00:58:39,400 KNOW ABOUT THIS INTERACTION, I 1752 00:58:39,400 --> 00:58:41,720 BET THERE'S A WAY THAT THE 1753 00:58:41,720 --> 00:58:45,440 BACTERIA GOES, NO, YOU DON'T. 1754 00:58:45,440 --> 00:58:47,720 AND NOBODY HAS THE RESOURCES YET 1755 00:58:47,720 --> 00:58:50,880 TO DO THE EXPERIMENTS. 1756 00:58:50,880 --> 00:58:53,160 I THINK CAN YOU DO SOME WITH 1757 00:58:53,160 --> 00:58:54,320 CULTIVATION INDEPENDENTLY, WE'VE 1758 00:58:54,320 --> 00:58:55,480 JUST NEVER HAD THE RESOURCES TO 1759 00:58:55,480 --> 00:58:56,000 DO IT. 1760 00:58:56,000 --> 00:58:58,480 OKAY. 1761 00:58:58,480 --> 00:58:59,280 >>ONE MORE ONLINE 1762 00:58:59,280 --> 00:59:02,520 THIS QUESTION IS FROM OUR 1763 00:59:02,520 --> 00:59:04,360 COLLEAGUE, HECTOR ROMERO. 1764 00:59:04,360 --> 00:59:05,480 HELLO, THIS WAS A FASCINATING 1765 00:59:05,480 --> 00:59:05,960 TALK. 1766 00:59:05,960 --> 00:59:07,800 I'VE WORKED WITH BACTERIA PHAGES 1767 00:59:07,800 --> 00:59:09,520 IN THE PAST AND HAVE ALSO BEEN 1768 00:59:09,520 --> 00:59:11,160 REALLY INTERESTED IN THE WAYS 1769 00:59:11,160 --> 00:59:12,880 THAT BACTERIA PHAGES FROM THE 1770 00:59:12,880 --> 00:59:14,480 SAME CLUSTER CAN VARY IN THE 1771 00:59:14,480 --> 00:59:22,840 WAYS THEY ACHIEVE LISOGENY. 1772 00:59:22,840 --> 00:59:24,080 THERE ARE THOSE THAT AFFECT THE 1773 00:59:24,080 --> 00:59:26,160 SAME HOST SPECIES BUT ONE MIGHT 1774 00:59:26,160 --> 00:59:28,360 AFFECT THROUGH LYSIS THE OTHER 1775 00:59:28,360 --> 00:59:29,000 PREFER INTEGRATE. 1776 00:59:29,000 --> 00:59:30,160 DO YOU THINK THAT THE 1777 00:59:30,160 --> 00:59:31,520 DIFFERENCES IN THE INTEGRATION 1778 00:59:31,520 --> 00:59:34,560 MECHANISMS USED BY 1779 00:59:34,560 --> 00:59:35,600 BACTERIOPHAGES IS ALSO RELATED 1780 00:59:35,600 --> 00:59:37,760 TO ALTERATIONS FROM THE 1781 00:59:37,760 --> 00:59:43,840 ENVIRONMENTAL ASSOCIATIONS? 1782 00:59:43,840 --> 00:59:45,920 >> I REALLY DON'T HAVE A 1783 00:59:45,920 --> 00:59:48,480 RESPONSE TO THAT. 1784 00:59:48,480 --> 00:59:49,480 >> I DON'T EITHER. 1785 00:59:49,480 --> 00:59:52,320 >> I THINK THAT'S A TOUGH 1786 00:59:52,320 --> 00:59:52,880 QUESTION. 1787 00:59:52,880 --> 00:59:54,440 IT'S AN INTERESTING POSSIBILITY, 1788 00:59:54,440 --> 00:59:55,680 BUT I DON'T THINK THERE'S ANY 1789 00:59:55,680 --> 01:00:00,080 DATA TO REALLY SPEAK FROM IN 1790 01:00:00,080 --> 01:00:00,560 RESPONSE. 1791 01:00:00,560 --> 01:00:01,640 >> AND ONE MORE, THEN WE CAN 1792 01:00:01,640 --> 01:00:02,720 WRAP UP? 1793 01:00:02,720 --> 01:00:02,920 >> SURE. 1794 01:00:02,920 --> 01:00:09,480 THANK YOU. 1795 01:00:09,480 --> 01:00:10,360 SO THANK YOU, THAT WAS REALLY 1796 01:00:10,360 --> 01:00:10,760 GREAT. 1797 01:00:10,760 --> 01:00:13,600 I JUST WAS WONDERING, TO FOLLOW 1798 01:00:13,600 --> 01:00:14,800 UP ON SUSAN'S QUESTION, GIVEN 1799 01:00:14,800 --> 01:00:16,520 THAT YOU'RE FINDING A LOT OF 1800 01:00:16,520 --> 01:00:19,800 PREF TA 1801 01:00:19,800 --> 01:00:21,480 PREVOTELLA WHERE THE LAK PHAGES 1802 01:00:21,480 --> 01:00:24,600 ARE DOES THAT MAYBE SUGGEST THE 1803 01:00:24,600 --> 01:00:29,680 PREVOTELLA IS FINDING A WAY TO 1804 01:00:29,680 --> 01:00:30,480 RESIST, MAYBE IT'S FOUND A WAY 1805 01:00:30,480 --> 01:00:31,120 TO SORT OF -- 1806 01:00:31,120 --> 01:00:32,000 >> GREAT QUESTION. 1807 01:00:32,000 --> 01:00:33,200 I GET YOU. 1808 01:00:33,200 --> 01:00:35,440 YES, THE ANSWER IS ACTUALLY 1809 01:00:35,440 --> 01:00:36,680 FIRST OF ALL, LET ME GO BACK TO 1810 01:00:36,680 --> 01:00:39,520 HOW WE IDENTIFIED PREVOTELLA AS 1811 01:00:39,520 --> 01:00:40,600 THE HOST FOR THE LAK. 1812 01:00:40,600 --> 01:00:45,080 THE ANSWER IS -- TARGETING, 1813 01:00:45,080 --> 01:00:45,800 THAT'S CRISPR. 1814 01:00:45,800 --> 01:00:47,800 BUT WE NEVER FOUND THE CRISPR 1815 01:00:47,800 --> 01:00:50,560 SPACES THAT CONFER IMMUNITY IN 1816 01:00:50,560 --> 01:00:51,920 THE SAME MICROBIOMES THAT WE 1817 01:00:51,920 --> 01:00:53,360 FIND THE LAK PHAGE. 1818 01:00:53,360 --> 01:00:58,360 WE USE CRISPR SPACE TARGETING TO 1819 01:00:58,360 --> 01:01:01,200 DO FIRST HOST-PHAGE LINKAGES FOR 1820 01:01:01,200 --> 01:01:01,640 10 MORE YEARS. 1821 01:01:01,640 --> 01:01:03,800 THIS IS ACTUALLY THE NORMAL 1822 01:01:03,800 --> 01:01:04,680 PATTERN. 1823 01:01:04,680 --> 01:01:06,920 THE PREVOTELLA THAT HAVE THE 1824 01:01:06,920 --> 01:01:08,840 LACK LAK 1825 01:01:08,840 --> 01:01:11,160 PHAGES HAVE DIED MOST PROBABLY, 1826 01:01:11,160 --> 01:01:12,920 BEEN PREDATED BEFORE THE LAK 1827 01:01:12,920 --> 01:01:13,320 PHAGES APPEARED. 1828 01:01:13,320 --> 01:01:14,880 WE HAVE TIME SERIES DATA TOO, SO 1829 01:01:14,880 --> 01:01:16,960 WE HAVE FOUR CONSECUTIVE-DAY 1830 01:01:16,960 --> 01:01:18,680 SAMPLES, SO THE LAK PHAGES ARE 1831 01:01:18,680 --> 01:01:20,120 REALLY CHANGING VERY QUICKLY, 1832 01:01:20,120 --> 01:01:21,960 THESE ARE VERY DYNAMIC SYSTEMS. 1833 01:01:21,960 --> 01:01:25,600 SO I WOULD SAY NO IMMUNITY, LAK 1834 01:01:25,600 --> 01:01:26,840 PHAGES PREVALENT. 1835 01:01:26,840 --> 01:01:29,160 IMMUNITY, WE DON'T FIND THE LAK 1836 01:01:29,160 --> 01:01:31,280 PHAGES, IT'S ONLY GOING ACROSS 1837 01:01:31,280 --> 01:01:32,040 THOSE TWO SAMPLE SETS WE CAN 1838 01:01:32,040 --> 01:01:32,840 MAKE THE CONNECTION. 1839 01:01:32,840 --> 01:01:35,440 SO THE IMMUNITY IS AT LEAST BY 1840 01:01:35,440 --> 01:01:36,840 CRISPR, MAYBE OTHER MECHANISMS 1841 01:01:36,840 --> 01:01:37,280 AS WELL. 1842 01:01:37,280 --> 01:01:39,880 BUT WE DON'T KNOW THE LIFE STOOL 1843 01:01:39,880 --> 01:01:40,520 OTHER THAN THERE'S NO EVIDENCE 1844 01:01:40,520 --> 01:01:42,760 THAT THEY INTEGRATE, THEY NEVER 1845 01:01:42,760 --> 01:01:44,200 BECAME PRO PHAGE, AS BEST AS WE 1846 01:01:44,200 --> 01:01:47,840 CAN SEAL FOR ANY OF THESE -- ANY 1847 01:01:47,840 --> 01:01:49,960 HUGE -- THAT WE KNOW THEY DO 1848 01:01:49,960 --> 01:01:51,560 THAT. 1849 01:01:51,560 --> 01:01:53,400 SO WHETHER THEY HANG AROUND AND 1850 01:01:53,400 --> 01:01:54,840 ARE SOMEHOW BENEFICIAL TO THE 1851 01:01:54,840 --> 01:01:56,680 HOST THAT MAKES THEM MORE LIKE A 1852 01:01:56,680 --> 01:01:57,800 PLASMID, I THINK THAT'S ON THE 1853 01:01:57,800 --> 01:01:58,400 TABLE STILL. 1854 01:01:58,400 --> 01:02:01,120 SO HOW DEFENSIVE THE PREVOTELLA 1855 01:02:01,120 --> 01:02:03,080 HAS TO BE IS ALSO IN QUESTION. 1856 01:02:03,080 --> 01:02:06,040 THANKS FOR THE QUESTIONS. 1857 01:02:06,040 --> 01:02:07,240 >> THAT'S WONDERFUL. 1858 01:02:07,240 --> 01:02:08,320 I GUESS WE'RE SUPPOSED TO FINISH 1859 01:02:08,320 --> 01:02:10,480 UP BECAUSE WE'VE HIT THE HOUR. 1860 01:02:10,480 --> 01:02:13,000 LOTS TO TALK ABOUT, REMIND 1861 01:02:13,000 --> 01:02:14,280 EVERYONE HERE AND ONLINE THAT 1862 01:02:14,280 --> 01:02:17,000 THERE WILL BE A LAMBDA LUNCH 1863 01:02:17,000 --> 01:02:19,200 CHAPTER 2 TOMORROW. 1864 01:02:19,200 --> 01:02:20,320 AND CONTACT SUSAN GOTTESMAN IF 1865 01:02:20,320 --> 01:02:21,960 YOU NEED THE LINK. 1866 01:02:21,960 --> 01:02:23,240 AND THANK YOU SO MUCH FOR 1867 01:02:23,240 --> 01:02:23,960 COMING. 1868 01:02:23,960 --> 01:02:25,520 IT'S BEEN WONDERFUL, A LOT OF 1869 01:02:25,520 --> 01:02:27,960 FUN AND LOTS OF THINGS TO KEEP 1870 01:02:27,960 --> 01:02:28,320 TALKING ABOUT. 1871 01:02:28,320 --> 01:02:30,200 [APPLAUSE] 1872 01:02:30,200 --> 01:02:31,120 >>THANK YOU. 1873 01:02:31,120 --> 00:00:00,000 THANKS FOR THE QUESTIONS.