>>WELCOME TO THE
WEDNESDAY AFTERNOON LECTURE
SERIES.
I'M KELLEY TENHAGUEIN, A SENIOR
INVESTIGATOR AT THE
BIOLOGY SECTION AT THE NATIONAL
INSTITUTE OF DENTAL AND
CRANIOFACIAL RESEARCH AND I'M
ALSO THE CHAIR OF THE WOMEN NIH
SCIENTIST ADVISORS COMMITTEE.
I AM EXCITED TO INTRODUCE
TODAY'S SPEAKER DR. CASSANDRA
EXTAVOUR, NOMINATED BY THE
NIH WOMEN ADVISORS.
OUR SPEAKER TODAY IS
DR. CASSANDRA EXTAVOUR, SHE IS
THE Ph.D. PROFESSOR WITH THE
DEPARTMENT OF ORGANIS MIC AND
EVOLUTIONARY BIOLOGY, DEPARTMENT
OF MOLECULAR AND CELLULAR
BIOLOGY HARVARD UNIVERSITY.
SHEES TALKING ABOUT EARLY
EMBIONIC DEVELOPMENT AND THE
GENES THAT CONTROL IT, THE
ORIGINS OF THESE
GENES AND HOW THEIR FUNCTIONS
HAVE CHANGED OVER EVOLUTIONARY
TIME.
IN STUDYING DROSOPHILA AND OTHER
NONTRADITIONAL MODEL ORGANISMS,
THE DOCTOR HAS UNCOVERED NOVEL
MECHANISMS IN GENERAL PRINCIPLES
OF EMBRYONIC GERMLINE AND GONAD
MORPH O GENESIS WITH CLEAR
IMPLICATIONS FOR UNDERSTANDING
HUMAN INFERTILITY.
SHE'S ALSO DISCOVERED WAYS THAT
ENVIRONMENTAL PRESSURES ON
REPRODUCTION CREATE HELP STEER
EVOLUTION, THE DOCTOR IS A
NATIVE OF TORONTO WHERE SHE WENT
ON TO ATTEND THE UNIVERSITY AND
OBTAIN A HONORS OF BATCHER
SCIENCE WITH MOLECULAR GENETICS
AND MOLECULAR BIOLOGY.
AND SHE PERFORMED POST DOCTORAL
WORK FIRST WITH [INDISCERNIBLE]
AT THE INSTITUTE OF MOLECULAR
BIOLOGY AND TECHNOLOGY IN CRETE
GREASE AND SUBSEQUENTLY WITH
MICHAEL THE UNIVERSITY OF CAME
BRIDGE.
IN.
2007, SHE ESTABLISHED HER
DEPARTMENT IN EVOLUTIONARY
BIOLOGY AT HARVARD WHY SMEE WAS
ROUGH ATOM PROTEIN COMPLEXED TO
ASSOCIATE PROFESSOR 2011 AND
FULL PROCESSOR IN 2014 AND THE
DOCTOR RECEIVED NUMEROUS HONORS
AND RECOGNITIONS INCLUDING BEING
SELECTED AS AN HHMI INVESTIGATOR
IN 2021 AS I MENTIONED EARLIER
AND ALSO RECEIVING THE ELLISON
NEW SCHOLAR AND AGING AWARD, IN
2020 SHE WAS NAMED HARVARD
COLLEGE PROFESSOR IN RECOGNITION
OF HER CONTRIBUTIONS TO
MENTORING AND TEACHING AT
HARVARD.
THE TITLE-THE DOCTOR'S TALK IS
EVOLVING ADAPTIVE REPRODUCTIVE
CAPACITY, A SYSTEMS APPROACH
USING DROSOPHILA MODELS.
OKAY, THAT'S CHANGED A BIT BUT
THAT'S OKAY.
AND DR. EXTAVOUR, WELCOME TO THE
NIH AND THANK YOU FOR BEING WITH
US.
>> THANK YOU SO MUCH KELLEY FOR
THE INTRODUCTION AND I WANT TO
THANK EVERYONE INVOLVED IN THE
INVITATION FOR ME TO BE HERE.
IT'S BEEN SCHEDULED FOR A LITTLE
WHILE NOW AND I'M EXCITED IT CAN
FINALLY TAKE PLACE.
I THINK HOPEFULLY WE'RE ALL
RELATIVELY USED TO THE VIRTUAL
FORMAT WHICH I THINK HAS A LOT
OF ADVANTAGES OF INCLUDING MORE
AND MORE PEOPLE.
SO I'M EXCITED TO TELL YOU
TODAY, ABOUT SOME OF THE WORK
WE'VE BEEN DOING IN MY LAB, 1
PARTICULAR LINE OF RESEARCH
THAT'S KIND OF GROWN AND BUILT
AND ADDED MANY DIFFERENT LAYERS
OF THE LAYERS WORKING ON IT AND
WE HOPE TO ADDED MORE LAYERS
GOING FORWARD, SO THAT'S WHY I
DECIDED TO SORT OF THINK ABOUT
THIS AS A SYSTEMS APPROACH
BECAUSE WE'RE TRYING TO
ENCOMPASS AS MANY DIFFERENT
ELEMENTS OF THE COMPLEX SYSTEM
OF BIOLOGICAL ORGANISMS AS WE
CAN IN OUR STUDY, WE CAN'T DO
EVERYTHING AT THE SAME TIME BUT
WE CAN DO A LITTLE BIT OF
EVERYTHING IF WE KEEP WORKING ON
IT LONG ENOUGH.
THE VIEW YOU'RE SEEING HERE ON
THE TITLE SLIDE IS THE VIEW,
IT'S NOT 1 OF OUR FIELD SITES, I
WOULD SAY IT'S A VIEW CAN YOU
HAVE ON THE WAY TO 1 OF OUR
FIELD SITES TO COLLECT SOME OF
THE ORGANISMS THAT WE WORK WITH
AS WE HAVE BEEN GUN TO WORK WITH
NATURAL POPULATIONS TO SORT OF
ENHANCE OUR WORK ON LABORATORY
POPULATIONS OF DROSOPHILA
SPECIES OF FRUIT FLIES.
SO YOU KNOW I'M INTERESTED IN
THE GENETIC AND EPIGENETIC
UNDERPINNING OF BIOLOGICAL
FUNCTION OF FORM AND DIVERSITY,
ALSO INTERESTED IN UNDERSTANDING
HOW ALL OF THESE SYSTEMS EVOLVED
AND SO WHEN WE CONSIDER THE
FUNCTION OF THE GENE OR THE
BEHAVIOR OF THE CELL, WE WANT TO
UNDERSTAND BOTH HOW THAT THING
IS WORKING IN A LIVING ORGANISM
AND ALSO HOW THE EVOLUTIONARY
PROCESS, THAT HAS TAKEN PLACE
BEFORE WE COULD REALLY OBSERVE
IT, KIND OF LED TO THAT
CHARACTERISTIC.
SO WHEN WE THINK ABOUT THE
EVOLUTION, WHICH IS HERITABLE
CHANGE OVER TIME WE KNOW WE NEED
3 MAIN THINGS FOR EVOLUTION TO
UPON HA, REALLY WE JUST NEED 2
EXPW THE THIRD IS A BONUS.
SOPHISTICATEDY WE NEED
VARIATION, IF EVERYTHING IS
IDENTICAL, THERE'S NO CHANGE TO
BE MADE AND SO EVOLUTION CAN'T
HAPPEN UNDER COMPLETELY STATIC
NO VARIANTS.
IF TERMS OF EVOLUTIONARY CHANGE
OR HERITABLE CHANGE WE NEED
THESE VARIATIONS TO BE
HERITABLE, THAT'S A KEY PILLAR
WITH JUST THOSE 2 ALONE CAN YOU
HAVE DIFFERENT PATTERNS OF
HERITABILITY OF VARIATION AND BY
DEFINITION EVOLUTIONARY CHANGE.
NONAPOPTOTIC YOU IF ANY OF THESE
VARIATIONS ARE ALSO LINKED TO
VARIATIONS IN FITNESS, THEN HAVE
YOU THE OPPORTUNITY FOR 1
PARTICULAR MECHANISM TO OPERATE
ON THE EVOLUTIONARY PROCESS AND
THAT IS NATURAL SELECTION.
I'M PARTICULARLY INTERESTED IN
THE LINK BETWEEN VARIATION AND
FITNESS, WHAT I MEAN BY THAT IS
IESM VERY INTERESTED IN TRAITS
WHOSE VARIABILITY DEFINITELY HAS
A LINK TO FITNESS BECAUSE THESE
ARE TRAITS THAT ARE SORT OF MORE
OBVIOUS CANDIDATINGS FOR THE
POTENTIAL FOR NATURAL SELECTION
TO THE ACTING BECAUSE OF COURSE
WE REMEMBER THAT NOT EVERYTHING
THAT'S PRODUCED IN EVOLUTION IS
PRODUCED BY ADAPTIVE FORCES
THEY'RE MANY NONADAPTIVE FORCES
THAT ARE VERY IMPORTANT BUT
TODAY I WANT TO SEE IF WE CAN
MAKE A STEP TOWARDS CONSIDERING
SOMETHING WE SUSPECT, IS OF
ADAPTED IMPORTANCE BECAUSE IT
IMPACTS FITNESS.
APPROXIMATE SO WE'RE INTERESTED
IN TRAITS THAT IMPACT
REPRODUCTION, OFFSPRING
REPRODUCTION BECAUSE THAT EAD
KEY ELEMENT OF FITNESS BECAUSE
IT'S A KEY ELEMENT OF THE NUMBER
OF OFFSPRING 1 PRODUCES IT WILL
HAVE A DIRECT IMPACT ON THE
NUMBER OF OFFSPRING IN THE NEXT
GENERATION THAT ARE CAN GOING TO
CONTAIN PARTICULAR VARIANTS OR
ALLELIC VARIATIONS AND WE
CONSIDER OFTEN SORT OF MANY
ASPECTS OF THE REPRODUCTIVE
PROCESS SINCE I SORT OF STARTED
AS A DEVELOPMENTAL BIOLOGIST, IT
MADE ME INTERESTED IN SCIENCE AS
A PROFESS, I THINK OF ALL LIFE
AS A DEVELOPMENTAL CYCLE, ALL
CELL LIFE AND 1 OF THE
DEFINITIONS OF LIVE OF
COURSE--TODAY THE PROCESS NEEDS
TO INVOLVE AT THE BEGINNING OF
DEVELOPMENT, THE SEPARATION OF
CELLS THAT WILL BE PALSZED ON
DIRECTLY TO THE NEXT GENERATION
SO THAT CELLS WILL MAKE GAM EATS
FOR EXAMPLE, NEED A GERMLINE
DISTINCTION.
YOU NEED TO GENERATE A BUNCH OF
SOMATIC CELL TYPES THIS IS AN
INVARIANT PROPERTY OF
MULTICELLULAR ORGANISMS LIKE
HUMANS OR FRUIT FLIES, THE
DEVELOPMENT PROCESS I'M USING AS
A HUGE BOX WITHIN WHICH ALL OF
THESE DIFFERENT CELL TYPES
ORGANIZE THEMSELVES INTO A
FUNCTIONING ENTITY AND ONCE YOU
ACCOMPLISHED THAT, CAN YOU
ACHIEVE YOUR PREPRACTICES
DUCTIVE OUTPUT THAT MIGHT BE
HIGH OR LOW REPRODUCTIVE OUTPUT
ASK THAT MIGHT CONTRIBUTE TO
YOUR HIGHER OR LOWER FITNESS.
TO GIVE YOU A SENSE OF HOW WE
LIKE TO THINK ABOUT THESE SORTS
OF PROBLEMS IN MY LAB BEFORE WE
GET INTO THE NITTY-GRITTY OF THE
SPECIFIC EXAMPLE, I WANT TO LET
YOU KNOW THAT WE LIKE TO THINK
OF THE EVOLUTIONARY PROCESS AND
IT'S SORT OF MANIFESTATION TODAY
ON MANY LEVELS OF BIOLOGICAL
ORGANIZATION.
WE THINK ABOUT GENES THEIR
SEQUENCES,Y WE THINK ABOUT THE
PRODUCTS THEY ENCODE, RNA'S
PROTEIN, WHAT HAVE YOU, WE THINK
ABOUT THE CELLS, AND HOW THEY
RESPOND TO THESE DIFFERENT GENE
PRODUCTS.
HOW THE CELLS PUT THEMSELVES
TOGETHER INTO ORGAN SYSTEMS, AND
HOW THESE ORGANS FUNCTION WITHIN
THE ORGANIZATIONSISMS AND
INCREASINGLY IN THE FUTURE, I
HOPE YOU'RE GOING TO MOVE THIS
SPOT TO OTHER LEVEL OF SORT OF
BIOLOGICAL ORGANIZATIONS WHICH
IS CONSIDERING ORGANISMS IN
THEIR NATURAL ENVIRONMENTS WHERE
THEY'RE HAVING MANY INTERACTIONS
WITH A LOT OF ORGANISMS.
WE TAKE A MULTIMODEL APPROACH
BECAUSE IF WE WANT TO UNDERSTAND
THE EVOLUTIONARY PROCESS BY
DEFINITION WE'RE TALKING ABOUT
HERITABLE CHANGE SO WE CAN'T
LOOK AT 1 ORGANISM, WE HAVE TO
LOOK AT A MINIMUM MANY
GENERATIONS OF AN ORGANISM AND
EVEN BET FERRANDIS OUR POINT OF
VIEW, MANY ORGANISMS BECAUSE
WHEN WE COMPARE THE SIMILARITIES
AND DIFFERENCES BETWEEN
DIFFERENT ORGANISMS WE CAN BEGIN
TO MAKE EDUCATED GUESSES WHICH
WE LIKE TOICAL HYPOTHESIS AS
SCIENTISTS AS TO THE
EVOLUTIONARY ORIGINS OF THE
THINGS WE'RE SEEING TODAY.
SO I WILL FOCUS IN TODAY'S TALK
TO WORK WE'VE DONE USING
DROSOPHILA MELANO GHASTER, AND A
NUMBER OF OTHERS SPECIES IN THE
LAB AND IN THE WILDER BUT OTHER
PEOPLE WORKING ON OTHER PROJECTS
I WON'T TALK ABOUT TODAY, WORK
ON OTHER MODELS THAT PEOPLE LIKE
TO CALL EMERGING MODELS BECAUSE
THEY'RE NOT AS ESTABLISHED OR
MAN EPIGENETICALATABLE LIKE THIS
HERE, YET WE TBIEND THEM VERY
FRUITFUL TO INVESTIGATE BECAUSE
THEY CAN OFFER US INSIGHT INTOS
NEW TYPES OF BIOLOGY AT THE
STANDARD WILL NEVER SHOW YOU.
SO THAT MEANS WE SOMETIMES SPEND
TIME DEVELOPING NEW MODELS IN
THE TRUE THAT WE SUSPECT HAVE
NEW INSIGHTS TO SHOW US THAT WE
CAN'T SEE WHEN WE'RE FOCUSING ON
THE PART OF THE TRUTH.
BECAUSE EVERYTHING WE DO
BUILDING ON HISTORICAL WORK,
MANY CENTURIES OF SCIENTISTS
BEFORE US, WE ALSO TAKE VERY
SERIOUSLY CONSIDERING THE
HISTORICAL LITERATURE WHERE THE
CENTURIES OF SCIENTISTS BEFORE
US HAVE COLLECTIVELY STUDIED SO
MANY MORE ORGANISMS THAN WE CAN
IN OUR LIFETIME AND WE DON'T
WANT TO NEGLECT THAT DATA SET
AND WE TAKE ADVANTAGE OF THAT
LITERATURE IN A BIG WAY AND
SOMETIMES AGAIN IT WILL NOT
ENTER INTO THIS TALK MUCH BUT
SIMULATING ORGANISMS IS VERY
USEFUL WAY JUST LIKE SIMULATING
ANY PROCESS, IS A VERY USEFUL
WAY TO UNDERSTAND THE SORT OF
LIMITS OF POTENTIAL EVOLUTIONARY
VARIATION AND TO GENERATE
INFORMED EXPECTATIONS AS TO WHAT
YOU MIGHT SEE IN THE EXTRA
POPULATIONS.
AND THEN FINALLY, WE'RE NOT AN
ORGANISM LAB, OR ORGANISM DRIVEN
LAB AS WE'VE SEEN AND NOT A
LEVEL OF BIOLOGICAL ORGANIZATION
DRIVEN LAB AND WE'RE ALSO NOT A
TECHNIQUE DRIVEN LAB AND SO, WE
USE WHATEVER TECHNIQUE WE THINK
IS GOING TO PROVIDE THE MOST
INSIGHT INTO THE LEVEL OF
ORGANIZATION THAT WE'RE
INTERESTED IN.
SO THAT MEANS THAT WE USE
DIFFERENT TOOLS GENETICS, WE USE
FIELD WORK, USE MICROSCOPY,
MODELING, BIOCHEMIST RADIOY,
WHATEVER WE THINK WILL ALLOW US
TO SHED LIGHT ON THAT PARTICULAR
ELEMENT OF BIOLOGICAL
ORGANIZATION THAT WE'RE
INTERESTED IN THIS A GIVEN
MOMENT.
SORRY, I WILL STOP FOR A MOMENT
TO LOOK FOR A MISSING SLIDE,
BECAUSE IT'S IMPORTANT AND
THAT'S TO TELL YOU ABOUT THE
PEOPLE WHO DID THE WORK.
THE TEAM
THAT BUILT UP THIS SYSTEM, THE
CORE MEMBERS ARE HERE AND
THEY'RE MEMBERS CURRENT AND
FORMER IN MY LAB OVER MANY YEARS
AND ANDRE GREEN WAS A FIRST
GRADUATE STUDENT ALONG WITH
[INDISCERNIBLE] THEY'VE GONE ON
TO BETTER AND BRIGHTER THINGS IN
MY LAB, AND ESTABLISHING KEY
PARAMETERS THAT CONTROL AND VERY
DEVELOPMENT IN DROSOPHILA AND I
WILL TALK ABOUT A LOT TODAY.
SAM CHURCH WAS A STUDENT WHO
JUST LEFT US REEBTLY FOR HIS
POST DOC.
--THAT POPULATION WORK IN HAWAII
WAS POWERED IN OUR LAB BY SARAH
SO THIS IS THE TEAM OF PEOPLE
THAT REALLY LAID THE FOUNDATIONS
FOR ALMOST ALL THE DATA I WILL
ARE SHARING WITH YOU TODAY OR
MANY YEARS.
ANDRE AND DIDEM WERE 2 OF MY
STARTING MEMBERS, AND THEY LAID
THE BASIS THAT WE'RE INTERESTED
IN WHICH WE WILL GO INTO MORE
DETAIL SOON.
SAM WAS ABLE TO GO OUT IN THE
WILD AND FIGURE OUT HOW DO IT
WITH THE COLLABORATORS AND SAM
PICKED UP THE BATON FOR HER AND
PUSHED FORWARD THE HAWAIIAN WORK
TOWARDS TODAY'S TALK AND THEN
TARUN AND LEO WERE GREAT WITHIN
THE LAB, AND TARUN IS A
BIOLOGIST ANDLY O IS A SYSTEM
BIOLOGIST AND THEY WORKED OUT
THE THOUSANDS OF PHENOTYPES AND
HUNDREDS OF DIFFERENT GENETIC
BACKGROUNDS TO PROVIDE US WITH
THE SYSTEMS LEVEL REGULATORY
INFORMATION THAT WE WERE ABLE IT
GET ABOUT THIS SYSTEM.
OKAY, SO THE SPECIFIC STUDY
SYSTEM NOW, THE SPECIFIC TRAITS
WE'RE TALKING ABOUT TO
UNDERSTAND THE EFLIEWGDZARY
VARIATION AND ORIGINS OF
VARIATIONS IN THESE TRAITS WE
WILL USE A SPECIFIC ASPECT OF
REPROUCT DIDDIVE ANATOMY OF
FRUIT FLIES AND THAT'S THE TYPE
CALLED THE OVALID AND
RELIABLEIOLE MPLET SO HERE ON
THE LEFT-HAND SIDE WE HAVE A
SCHEMATIC OF THE FRUIT FLY, IT
HAS A BILATERALLY SYMMETRICAL
OVARY INSIDE IT WHICH IS THE
WHITE THING AT THE BOTTOM AND WE
TAKE OUT 1 OF THESE AND LOOK AT
IT CLOSE UP WE SEE CAN THAT
UNLIKE A MAMMALIAN OVARY, WHICH
IS A BAG OF
DISORGANIZATIONALINIZED CELLS IN
THE SIDES AND THE CELLS INSIDE
ARE AT DIFFERENT STAGES OF PHOTO
GENERATED CISION BUT THERE'S NOT
ANATOMICAL ORGANIZATION WITHIN
THAT BUT IN INSECTS THEY'RE
ORGANIZED ABOUT THEIR OVARIES,
THEY DIVIDE THEM INTO AN
ASSEMBLY LINE WHERE THE EGGS ARE
MADE AND THESE LINES ARE CALLED
CORRELATED VALID AND
RELIABLEIOLES AND YOU CAN SEE ON
THE RIGHTED HAND SIDE.
SO THESE IS ORGANIZED IN THE
WILL IFING WAY AT THE ANTERIOR
AT THE TOP, WE HAVE GERMLINE
STEM CELLS THAT ARE CONTINUALLY
PRODUCING SOURCES OF NEW
OSIGHTS, THESE ARE PRODUCED
INITIALLY AT THE TOP AND THEY
DIFFERENTIATE AND BECOME MORE
AND MORE MATURE AS WE MOVE
TOWARDS THE MOSTERIOR AND THEY
ARE COMPLETELY MATURE AND
ACTIVATED AND FERTILIZED AND
THEY ARE LAID AT THE BOTTOM OF
THE FLY OR POSTERIOR.
SO THIS TRAIT NOW OVALID AND
RELIABLEIOLES IN THE NUMBER OF
OVALID AND RELIABLEIOLES IS A
VERY INTERESTING TRAIT BECAUSE I
WILL SHOW YOU IN THE NEXT COUPLE
SLIDES IT INVOLVES KEY FEATURES
THAT WE WOULD LIKE TO SEE IN A
TRAIT WHOSE EVOLUTION MAY BE
ADAPTED THAT MEANS MAY CONVERG
WITH THE SPECIFIC FITNESS
ADVANTAGES INTO THE SPECIFIC
ENVIRONMENTS IS SO WE WILL LOOK
AT A OVALID AND RELIABLEIOLE
NUMBER BECAUSE WE THINK IT
PROVIDES A DIRECT LINK TO THE
FITNESS AND I WILL SHOW YOU
EVIDENCE FOR THAT THOUGHT IN A
SECOND.
SO, DOES OVARIOLE CHANGE?
YES, AT THE END OF THE TALK
OVARIOLE ACROSS INSECTS IS
EXTREMELY VARIABLE, SEVERAL
NUMBERS BUT EVEN WITHIN THE DROF
SOLILLA WE CAN CHANGE IT BY A
COUPLE ORDERS OF MAGNITUDE
ALONE.
HERE YOU'RE SEEING A SET OF
EVOLUTIONARY RELATIONSHIPS
BETWEEN 12 DIFFERENT SPECIES OF
THE GEANUS DROSOPHILA AND THE
OVARIOLE NUMBER IS THE TOTAL
NUMBER PERFEMALE AND WE FIND
THAT THE OVARIOLE NUMBER IS
SIGNIFY LATERALLY SYMMETRICAL,
SO THE OVARIOLE IN 1 OVARY WILL
BE HALF OF THIS.
SO SHOWN UP HERE CLOSE TO THE
TOP THAT HAS HALF THE NUMBER OF
THE OVARIOLE ALTHOUGH SOME OF
ITS RELATIVES, ARE SIMILAR.
SO WE HAVE A LOT OF VALID AND
RELIABLE YABTS TO TO WELCOMER
WITH SO EVOLUTION LOOKS
PROMISING.
WE HAVE HIGH HERITABILITY OF
THIS TRAIT.
THIS CAN BE INFLUENCED BY
PARAMETERS AS YOU WILL SEE IN 20
MINUTES OR SOMETHING, BUT LET ME
TELL YOU IT IS STRONGLY
GENETICALLY DETERMINED AND
HERE'S EVIDENCE FOR THAT, IN
THIS EXPERIMENT WHAT WE DID WAS
GO TO HAWAII, AND FIND FLIES
THAT NATURALLY ARE LIVING AND
THEREFORE WE THINK FEEDING ON
DIFFERENT TYPES OF SUBSTRATES,
FLOWER, SAP, ET CETERA.
THEY ARE LISTED AT THE TOP AND
WE CATCH THESE WILD CAUGHT
FEMALES WE DON'T KNOW WHAT
THEY'VE BEEN EATING, MATING
WITH, AND WE CATCH THEM, AND
BRING THEM BACK TO THE WILL BE,
GIVE THEM STANDARD FLY FOOD, TO
LAY THEIR EGGS ON IT, AND THEY
LAY THEIR EGGS IN LAB, THEIR
EGGS ARE HAPPY TO DEVELOP ON OUR
FOOD.
A NUMBER OF THESE WILD CAUGHT
MOTHERS THAT WERE EATING
WHATEVER THEY WANTED AND
WHATEVER ENVIRONMENT THEY FELT
LIKE, WE CAN COMPARE THEIR
OVARIOLE NUMBER TO THE OVARIOLE
OF THEIR OFFSPRING AND WE FIND
NOTICE SIGNIFICANT DIFFERENCE
EVEN THOUGH THE MOMS WERE EATING
WHATEVER THEY WANTED AND THE
OFFSPRING WERE EATING THE SAME
THING IN THE LAB CONDITIONS BUT
NEVERTHELESS THE NUMBER IS NOT
STATISTICALLY DIFFERENT.
SO THIS IS TELLING US WE HAVE A
HUGE AMOUNT OF GENERATEDETEC
CONTROL OVER THIS TRAIT.
SOPHISTICATEDY THAT'S 2 CHECK
MARKS FOR EVOLUTIONARY CHANGE
RIGHT NEW WE KNOW WE CAN GET IT
IN THIS TRAIT AND FINALLY WE
THINK EVOLUTION EAR CHANGE OVER
TIME MAY ACTUALLY BE ADAPTIVE IN
SUCH SITUATIONS BECAUSE IN
DROSOPHILA, THE MORE OVALID AND
RELIABLEIOLES HAVE YOU, THE MORE
EGGS YOU GET TO LAY, THIS
EXPERIMENT HERE, THESE DATA ARE
SHOWING YOU, THE RESULTS OF AN
EXPERIMENT WHERE WE USE GENETIC
TRICKS FOR THE [INDISCERNIBLE]
TO MAKE THE FLIES HAVE MORE AND
MORE OVARIOLES.
SO IF YOU LOOK AT THE RIGHT
PLOT, THE WILD TYPE IS AT THE
TOP AND IT HAS A CERTAIN NUMBER
OF OVARIOLE AND IN THE SECOND
ROLE, YOU SEE WE MANIPULATED THE
FLIES GENETICALLY, THE DETAILS
ARE NOT IMPORTANT BUT WE
INCREASED THE NUMBER SO THE BAR
IS SHIFTING TO RIGHT, AND
CORRESPONDINGLY IF YOU LOOK AT
THE LEFT HAND SPOT WHERE WE'RE
LOOKING AT THE TOTAL NUMBER OF
EGGS LAID BY THESE FEMALES
THEY'RE LAYING MORE THAN WHEN
THEY DID HAVE FEWER OVALID AND
RELIABLEIOLES AND WE CAN DO MORE
GENETIC TRICKS IN THE BOTTOM
REAL AND GIVE THEM A HIGHER
NUMBER AND CORRESPOND WHEN
THEY'RE GOING TO LAY MORE EGGS.
OVER HERE YOU CAN SEE MORE
EVIDENCE, FURTHER THAT THAT
NUMBER IS STRONGLY POSITIVE LE
CORRELATED WITH EGG LAYING IN
SOME IN60S INCLUDING DROSOPHILA.
SO OUR LABORATORY NORTH AMERICAN
CONTROL STRAIN OF THIS HAS ABOUT
40 OVALID AND RELIABLEIOLES
PERFEMALE AND IN OUR LABDS SHE
WILL LAY 50 TO A HUNDRED EGGS A
DAY GIVE OR TAKE, THIS OTHER
SPECIES, THIS CRICKET HAS AN
ORDER OF MAG NIITUTE OF OVARIOLE
AND IT LAYS MORE EGGS AND IN
CLOSELY RELATED SPECIES, THESE 2
SPECIES, THE MELANOGASTROON THE
TOP AND THE SEC HELLIA,OT
BOTTOM, IT ONLY HAS HALF THE
NUMBER OF OVARIOLE COMPARED TO
MELANOGASTER, AND IT LAYS FAR
FEWER EGGS AND IT SHOWS THE
FIRST 10 DAYS OF LIFE AND WE
COUNT UP THE EGGS THAT THESE
FEMALES LAID EVERY DAY OF THEIR
FIRST 10 DAYS OF LIFE, THE
NUMBER OF EGGS ON THE Y-AXIS AND
YOU CAN SEE FOR THESE 2 DAYS
THESE PLIES LAY VERY DIFFERENT
NUMBERS OF EGGS, EACH 1 IS A
FEMALE WE COUNTED.
THIS IS A SMALL DATA PILOT SET
WHERE WE HAD 10 PER SPECIES AND
WE COUNTED FOR DEN DAYS AND
COLLECTED A LARGER DATA SET WITH
A HUNDRED FEMALES PER SPECIES
OVER THEIR ENTIRE LIFETIME.
WE COUNTED HOW MANY THEY ALL
LAID UNTIL THEY DIED SEC HELLIA
NEVER CATCHES UP.
IT WILL ALWAYS LOSE OUT THERE SO
WE HAVE QUANTITATIVE TRAIT.
HIGHLY HERITABLE AND LINKED TO
FITNESS AND START TO INVESTIGATE
THE NUMBER OF DIFFERENT
QUESTIONS ABOUT HOW THIS
STRAIGHT GETS TO BE THE WAY IT
IS IN SPECIFIC SPECIES AND HOW
VARIATIONS IN THIS TRAIT MIGHT
POSSIBLY HAVE EVOLVED.
SO WE'RE GOING TO LOOK AT IT
FROM AT LEAST 3 DIFFERENT POINTS
OF VIEW AND I WILL GIVE YOU
EXAMPLES OF THE SORTS OF
EXPERIMENTS THAT WE DO WHEN
WE'RE CONCERNED WITH THE
DEVELOPMENTAL CONTROL OF THE
TRAIT, THE GENETIC CONTROL OF
THE STRAIGHT AND THE
ENVIRONMENTAL CONTROL OF THE
TRAIT.
SO WHEN WE THINK ABOUT
DEVELOPMENTAL CONTROL OF THE
TRAIT, WHAT I MEAN BY THAT IS
WHAT ARE THE CELLS THAT NEED TO
MAKE THE ON OVARIOLE, WHAT DO
THE CELLS DO THAT MAKES THENL
DECIDE HOW MANY THEY NEED TO
MAKE?
WHAT YOU ARE SEEING HERE WILL BE
CLEAR SHORTLY.
IT'S A MICROGRAPH OF A LARVA
OVARIOLE, BEFORE THE OVARIOLE
ARE EVEN FINISHED AND YOU CAN
SEE THAT THERE ARE A LOT OF
DIFFERENT CELL TYPES, EXPRESSING
JEEPS, DIFFERENT COLORS, THE
GENES ARE NOT IMPORTANT, THEY'RE
ORGANIZING THEMSELVES IN A WAY
THAT I WILL SHOW YOU CORRESPONDS
TO THE NUMBER THAT THESE OVARIES
GOING TO GIVE RISE TO.
SO A VARIABLE NUMBER IT TURNS
OUT, IT'S ASH ADULT TRAIT WE'RE
INTERESTED IN BUT IT'S
DETERMINED DURING THE LARVAL
STATES IN THIS INSECT SO DURING
THE EMBRYO, THE ANIMAL MAKES A
GONAD, AND AT THIS POINT AS FAR
AS WE CAN TELL UNDIFFERENTIATED
THESE SOMATIC CELLS.
AS THE LARVA GROWS, SO THE
DIFFERENT NUMBERS OF DIFFERENT
STARS OR DIFFERENT LARVAL
STAGES, YOU GET MORE CELLS AND
THESE REORGANIZE THEMSELVES ON
THE STOP NOW, THE WHITE CELLS
AND THE GERM CELLS ARE ALL DOWN
AT THE BOTTOM OR THE POSTERIOR
AND THE HANDFUL OF CELLS TURNED
GREEN, THESE ARE ALL A SPECIAL
TYPE OF SOMATIC CELL AND THEY
HANG OUT OR A INTERMINGLE WITH
THE CELLS.
SO THE SOMATIC CELLS ARE MOVING
IF ZINDER KACCT WILY AND THEY'RE
STARTING TO BECOME DIFFERENT IN
THEIR IDENTITY IN THEIR
BEHAVIOR.
THEY BEGAN TO EXPRESS DIFFERENT
JEERNS IN THOSE NEIGHBORS, THOSE
ARE THE RED CELLS, THOSE CELLS
THEY'RE EXPRESSING OTHER JEANS
I'M NOT SHOWING MORE COLORS HERE
BUT THEY'RE STARTING TO MOVE
DOWN BESIDE THE GERM CELLS SO
THERE'S SOME VIBRATION HAPPENING
AND THESE CELLS CHANGE SHAPE
NOW, THEY BECOME INSTEAD OF
BEING ROUND THEY BECOME FLAT AND
THEY STACK UP ON TOP OF EACH
OTHER, MIGRATING CELLS ON THE
RIGHT SIDE, POSTERIOR OF THE
OVARY AND FINALLY WHAT WE CALL
THE LP TRANSITION WHICH IS THE
LARVAL PIEWPA TRANSITION THIS IS
WHEN THE ANIMAL'S ABOUT TO HEAD
INTO MAKING A PUPA BEFORE THE
FINAL STAINCH BEFORE ADULTHOOD,
AND THE CELLS THEY MADE THE
STACKS CALLED TERMINAL FILAMENTS
THEY ARE CRITICAL BECAUSE THE
NUMBER OF TERMINAL FILAMENTS
THAT AN ANIMAL HAS WHEN THEY GO
INTO PUBLISHEDIPATION, WITH IT
WILL HAVE AN EFFECT ON WHAT
HATCHES OUT AS AN ADULT.
AND THIS UNDERSTANDS IN ADULT
FLIES WE NEED DEVELOPMENTAL
BIOLOGIST IS THE CELL BEHAVIOR
THAT TAKES PLACE DURING LARVAL
STAGES IN THE OVARY.
HERE'S MICROGRAPHS TO SHOW YOU
WHAT THEY LOOK LIKE TO US UNDER
THE MICROSCOPE, THIS IS SHOWING
THE OVARY, NUCLEI ARE IN BLUE
AND THE FILAMENT CELLS ARE IN
RED AS THEY BEGIN TO ACQUIRE
IDENTITY AND THEY TURN ON
SPECIAL GENES AND CALLED
ENGRAILED FOR THOSE WHO LIKE TO
KNOW GENE NAMES, THE CELLS ARE
CHANGING THEIR SHAPE AND
BECOMING FLATTENED AND DISK
SHAPED.
THEY STAM UP INTO LITTLE STACKS
THAT WE OUTLINED WITH A WHITE
DOTTED LINE FOR YOU TO SEE MORE
CLEARLY WITH THE RESULT THAT BY
THE TIME IT GOES IN THERE, THIS
OVARY NOW HAS THE SAME NUMBER OF
TOURNAMENT FILAMENT STACKS AS IT
WILL HAVE IN THE ADULT SO THIS
IS HOW IN 1 SPECIES OOVARIOLES
GET MADE AND DETERMINED IS BY
DETERMINING THE NUMBER AND
ORGANIZATION OF THESE CELLS.
WHAT HAPPEN FIST WE LOOK AT 2 OR
MORE SPECIES WHOSE NUMBERS ARE
DIFFERENT EXPW WE GO BACKWARDS
IN TIME AND TRY TO FIND THE
POINT DURING LARVAL
DEPRIVATIONMENT WHEN THEY BEHAVE
DIFFERENTLY IN THE DIFFERENT
SPECIES TO GIVE US THE RESULT
THAT AS AN ADULT THEY HAVE THE
DIFFERENT TRAITS.
WE CHOSE FRS THIS STUDY, TO ROOK
AT EVOLVING DEVELOPMENT WITH A
SPECIES.
THE NUMBERS ON THE RIGHT HAND
SIDE TO THE RIGHT OF EACH
SPECIES NAME ARE THE NUMBER OF
OVARIOLE OF AN ADULT FEMALE OF
THIS SPECIES AND THE NUMBERS IN
THE YELLOW BOXES ARE THE NUMBERS
THAT WE INFER THROUGH
AN ANCESTRAL STATE
RECONSTRUCTION, THE LAST COMMON
ANCESTOR THESE SPECIES MIGHT
HAVE HEAD AND WE AND SEE THAT WE
FOCUS DOWN ON THE BOTTOM OF THE
TREE HERE, DROSOPHILA, THAT'S
OUR TYPE HERE, OR OREGON OUR
REFERENCE STRAIN HAS ABOUT 36
OVARIOLES IN A FEMALE.
ANOTHER STRAIN OF MELANO
GHASTER, IS A SAME SPECIES
LIVING IN INDIA HAS A MUCH LOWER
NUMBER OF OVARIOLE, 24, AND NOT
A DIFFERENT STRAIN OF THE SAME
SPECIES BUT A DIFFERENT SPECIES
ENTIRELY, SO DOWN AT THE BOTTOM
AS YOU HEARD BEFORE, IT HAS MANY
FEWER OVARIOLA THAN MELANO
GHASTER AND WHAT WE'RE LOOKING
AT IS THE EVOLUTION,
INDEPENDENTLY IN THESE 2
DIFFERENT LINEAGES OF A LOWER
OVARIOLE NUMBER COMPARED TO THE
LAST COMMON ANCESTRAL NUMBER IN
THIS GROUP WAS AROUND 32 OR
SOMETHING LIKE THAT IN THE
BRIGHT YELLOW CONTROLLER OF
BANK.
SO WHAT ANDRE DID HERE IS HE
LOOKED CAREFULLY, COUNTED THE
NUMBER OF CELLS, DOCUMENTED
THEIR BEHAVIOR IN THE LARVAL
DEVELOPMENT OF THE OVARY OF ALL
3 LINEAGES, 2 SPECIES OF MEL AN
GHASTER AND 1 WITH HIGH AND LOW,
AND SOME SHELLIA WITH THE LOW
NUMBER AND HE ASKED DO THEY HAVE
LOWER NUMBERS THAN THE OTHER
LINEAGE FOR THE SAME
DEVELOPMENTAL REASONS?
THE THINGS THAT THEIR CELLS DID
DIFFERENTLY ARE THOSE THINGS THE
SAME BETWEEN THOSE LINEAGES OR
ARE THEY DIFFERENT BETWEEN THOSE
LINLIAGES.
>> AND THE ANSWER IS, THEY'RE
DIFFERENT.
IN OTHER WORDS THERE ARE MANY
DIFFERENT WAYS CAN YOU LOWER
OOVARIOLE NUMBER, THERE ARE MANY
DIFFERENT CHOICES THE CELLS CAN
MAKE WITH THE RESULT THAT THEY
WILL HAVE FEWER, THAN SOME
RELATIVE, THIS IS THE BEGINNING
OF THE DEVELOPMENT OF 3
LINEAGES, INDIA ON THE LEFT,
OREGON IN THE MIDDLE AND SHELLY
ON THE RIGHT.
ANDRE COUNTED UP THE TOTAL
MEMBER OF AMOUNT IN THE OVARY IN
THE LARVAL DEVELOPMENT AND SAW
THAT SHELLIA WILL HAVE A VERY
LOW NUMBER AS AN ADULT INDEED
HAS A SMALLER NUMBER OF THAT
SOMATIC CELLS AT THE BEGINNING
OF THE ITSELF DEVELOPMENT, THE
OTHER 2, LINEAGES WHICH ARE THE
SPECIES FOR DROSOPHILA MELANO
GHASTER, HAVE THE SAME NUMBER,
BECAUSE THAT'S INTERESTING
BECAUSE WE'RE EXPECTING INDIA TO
GROW UP AND HAVE FEWER OVARIOLE,
BUT WHEN IT'S GROWN UP IT HAS
THE SAME NUMBER.
ANDRIE COUNTED UP THESE CELLS
AGAIN, AND WE FOUND THAT AS WE
MIGHT EXPECT THIS HAS FEWER
CELLS IN ITS OVARY THAN MELANO
GHASTER, SO SHELLY STARTED OUT
WITH FEWER, IT WILL END UP WITH
FEWER AND IT WAS NOT ABLE TO
CATCH UP IN THE LARGER STAGE.
IT STARTS SMALL, STAYS SMALL.
BUT THE IBDIA STRAIN IS
INTERESTING BECAUSE WE KNOW IT
WILL HAVE FEWER OVARIOLES THAN
THE NORTH AMERICAN COUNT'RE
COUSIN AND WHEN IT'S TIME TO
MAKE A PIEWPA THIS OVARY HAS WAY
MORE CELLS IN IT THAN THE MELANO
GHASTER DOES AND YOU CAN SEE
THAT AS THIS MASSIVE OVORY, SO
WHY IS IT NOT MAKING TERMINAL
ILAMENTS.
IT TURNS OUT IT'S ALLOCATED
THESE DIFFERENTLY.
YOU MIGHT REMEMBER THAT WHEN WE
WERE LOOKING AT THE CARTOON OF
LARVAL DEVELOPMENT THERE'S A
BUNCH OF CELLS, SOMATIC CELLS
THAT START ANTERIOR TO THE GERM
CELLS AND THEY MIGRATE DOWN TO
THE POSTERIOR, IT TURNS OUT THAT
GROUP OF CELLS IS MUCH BIGGER IN
INDIA, THAN IT IS IN MELANO
GHASTER KYOU STILL SEE MY
SCREEN, IT STARTED SOMEONE ELSE
STARTED SCREEN SHARING.
>> INDEED THAT, IS THE CASE, I
DON'T KNOW WHAT'S HAPPENING.
MAYBE YOU CAN RESHARE YOUR
SCREEN.
>> OKAY, I DOLL THAT.
--SORRY I DON'T KNOW WHAT
HAPPENED.
>> SO WITH THE INDIA SERIES, IT
SEN ILLEGALSEN WAY MORE THAN IT
HAD TO THE PESTERIOR OF THE GERM
CELLS, IT LEFT A SMALLER
PROPORTION OF CELLS IN THE
ANTERIOR REGION WHERE THE CELLS
HAVE TO COME FROM.
AND SO, THIS LITTLE STUDY TOLD
US THAT THERE ARE A LOT OF
DIFFERENT CELL DECISIONS THAT
YOU CAN MAKE AND THAT CAN YOU
CHANGE OVER EVOLUTIONARY TIME TO
END UP WITH A DIFFERENT RESULT,
DEPENDING ON THE LINEAGE THAT
YOU'RE IN.
NOW 1 THING THAT DIDUM WANTED TO
KNOW WHEN SHE WENT TO HAWAII FOR
THE FIRST TIME IF THE KEY
PARAMETER THAT CONTROLS IT IN
THE DROSOPHILA MELANO GHASTER IS
THAT KEY PARAMETER ALSO A KEY
PARAMETER THAT CORRELATES WITH
VARIABLE NUMBER IN NATURAL
POPULATIONS.
SO TO ANSWER THOSE QUESTIONS,
SHE WENT TO HAWAII, SHE
COLLECTED A BUNCH OF DIFFERENT
SPECIES THAT ALL HAD VERY
DIFFERENT OVARIOLE NUMBERS SO
THE OVARIOLES ARE PLOTSOT BOTTOM
AND SHE COUNTED THEM UP IN
LARVAL STAGES WHICH YOU CAN SEE
ON THE GRAY PLOTS ON THE TOP AND
YOU CAN SEE THEREYA A PERFECT 1
TO 1 CORCALCULATIONS BETWEEN THE
NUMBER OF TOURNAMENT FILAMENTS
YOU MAKE AND THE TOTAL NUMBER OF
OVARIOLE YOU WILL HAVE EVEN IN
THESE WILD POPULATIONS SO THIS
SUGGESTION WE WERE GETTING FROM
OUR LAB SPECIES, THE TOURNAMENT
FILAMENT CELL NUMBER IS THE CELL
BIOLOGY PARAMETER TO CONTROL THE
NUMBER, THIS OBSERVATION SEEMS
TO HOLD UP FOR THESE NATURAL
POPULATIONS.
OKAY, LET ME TELL YOU ABOUT SOME
OF THE WAYS THAT WE LOOK AT THE
GENETIC REGULATION OF A NUMBER,
HOW DO WE FIGURE OUT WHAT JEERNS
CONTROL THE NUMBER OF OOVARIOLES
AND HOW THOSE GENES AND THEIR
ACTIVITIES MIGHT BE CHANGE
NOTHING DIFFERENT SPECIES TO
GIVE US RESULTSA THE END.
THIS IS A LITTLE SCHEMATIC, 1 OF
THESE HIDEOUS SIGNALING
DIAGRAMS, IT SHOWS SOME OF THE
DIFFERENT SIGNALING PATHWAYS
THAT WERE KNOWN TO BE INVOLVED
IN SETTING UP THE CORRECT NUMBER
AND ORIENTATION AND ARRANGEMENT
OF THESE DIFFERENT KEY CELL
TYPES IN THE OVARY 10 YEARS AGO
SO SOMETHING WHEN WE STARTED
THIS WORK SO TOURNAMENT FILAMENT
CELLS IN RED, INTERMINGLED GERM
CELLS AND NUMBERS AND PLACEMENT
ARE THESE TO GET THE CORRECT
OVARIOLE NUMBER, DIDUM DID A
NICE STUDY SHOWED THAT HIPPO
SIGNALING THAT IS A RECENTLY
DISCOVERED PROLIF CONTROLLER
SIGNALING PATHWAY IN ANIMALS
ALSO PLAYS A KEY ROLE IN THIS
SYSTEM, BY CONTROLS THIS, AND
NOW WE KNOW THAT THERE'S NO
SINGLE JEERN THAT CONTROLS ANY
SINGLE TRAIT.
SO WE TOOK ADVANTAGE OF THE NEW
KNOWLEDGE THAT WE HAD THAT HIPPO
SIGNALING WAS INVOLVED IN
REGULATING THE FILAMENT AND WE
ASKED WHAT OTHERS MIGHT AFFAIRS
TEAM LEADERRER THIS WITH HIPPO
OR INDEPENDENTLY OF HIPPO.
AND SO FOR THE FLY NERDS IN THE
AUDIENCE WE DID A CLASSIC SORT
OF SUPPRESSION JEAN, AND
ENHANCER SCREEN AND HIPPO LOSS
OF FUNCTION BACKGROUND AND WE
SYSTEMATICALLY KNOCKED OUT
RNACKING I, ALL OF THE SIGNALING
PATHWAYS SO 800 GENES 1 AT A
TIME WE KNOCK THEM OUT IN A WILD
TYPE BACKGROUND AND A HYPOLOSS
OF FUNCTION BACKGROUND AND ASKED
IF THIS AFFECTED THE OVALID AND
RELIABLEIOLE NUMBER OF THE FLIES
AND IF IT AFFECTED THE EGG
LAYING SO WE HAVE 2 DIFFERENT
REPRODUCTIVE TRAITS WE'RE
LOOKING AT HERE AND IF YOU ARE
WORKING ON A SIGNALING PATHWAY
AND YOU ARE WONDER FIGURE YOU'RE
SIGNALING PATHWAY WAS INVOLVED
IN THE OVARIOLE DETERMINE
NATION, THE ANSWER IS YES
BECAUSE EVERY CONSERVED ANIMAL
SIGNALING PATHWAY IS INVOLVED IN
OVALID AND RELIABLEIOLE NUMBER
OF DETERMINE NATION, IT TURNS
OUT.
ONE OF THE WAYS WE THOSE TO LOOK
AT THIS SCREEN, WAS TO LOOK AT
IT FROM A SYSTEMS BIOLOGY LENS
THROUGH THE PERSPECTIVE OF
ASKING--AND THERE PROTEIN,
PROTEIN IRPT ACTIONS WHICH
SUGGESTS SOME TYPE OF GENE
REGULATORY RELATIONSHIP.
SO LEO TOOK THE KNOWN PROTEIN
PROTEIN INTERACTIONS AND SUPER
IMPOSE THAD ON TO THE RESULT OF
OUR FUNCTIONAL SCREEN HERE FOR
THE DIFFERENT FEIGNEE TYPES WE
LOOK AT, EGG LAYING AND HIPAA O
NUMBER AND IN A WILD TYPE
BACKGROUND AND WHAT HE
DISCOVERED WAS THAT THERE WERE
CERTAIN GENES THAT INTERACT WITH
EACH OTHER MORE AWNCH THAN YOU
WOULD EXPECT BY CHANCE THAT ALSO
IMPACT THE SAME PHENOTYPE, MORE
OFTEN THAN YOU WOULD EXPECT BY
CHANCE.
THESE MORE OFTEN THAN YOU WOULD
EXPECT BY CHANCE RELATIONSHIPS
SUGGIEST TO US THAT THESE MIGHT
BE CONSERVED, FUNCTIONAL GENE
REGULATORY NETWORKS THAT GENES
THAT WORK TOGETHER TO CONTROL
THESE SPECIFIC TRAITS.
WE FOUND GENES THAT WORK
TOGETHER TO CONTROL BOTH OF THE
TRAITS THAT WE LOOKED AT.
THEY SHUT DOWN OVARIOLE AND EGG
LAYING OR THEY RAISE OVARIOLE
AND EGG LAYING TOGETHER, SORT OF
AN ALL OR NOTHING GROUP.
SO WE ALSO FOUND SUBMODDULES
HERE WHICH WERE SMALLER GROUPS
OF GENES THAT TOGETHER APPEAR TO
REGULATE JUST 1 ELEMENT OR JUST
SORT OF LIKE 1 LEG OF THE
PHENOTYPE, LIKE THIS GROUP OF
GENES UP HERE AT THE TOP, IT
REGULATES ONLY IN THE HIPAA LOSS
OF FUNCTION BACKGROUND, THESE
GROUPS OF GENES HERE AND SO ON
FOR THESE DIFFERENT PHENOTYPES
THAT WE SCORE.
THE MOST EXCITING PART OF THIS
SCREEN HERE WAS NOT TO DISCOVER
THAT SOME OF THE JEERNS WE
TESTED FOR FUNCTION ACTUALLY
FUNCTION, I MEAN WE KNEW WE WERE
GOING TO GET SOMETHING, BUT
WHAT'S EXCITING ABOUT THIS
ANALYSIS WHICH WAS THAT BECAUSE
IT KEPT IN MIND ALL KNOWN
PROTEIN, PROTEIN ISHT ACTIONS
PRACTICES THE ENTIRE DROSOPHILA
GENOME, NOT JUST THE 1S WE
SCREEN BUT ALL OF THEM, IT WAS
ABLE PREDICT FOR US THE CONNECT
OR GENES IN THE POPPOLOGY
ANALYSIS, THESE ARE GENES WE
HADN'T TEST INDEED OUR SCREEN
BUT ACCORDING TO THE NETWORK
ANALYSIS WE DID, THEY SHOULD BE
INVOLVED IN VERY SPECIFIC
PHENOTYPES BECAUSE YOU CAN SEE
THAT SOME DOTS ARE BLUE AND SOME
ARE AND SOME AREN'T AND THEN
WHAT WE DID IS WE TESTED ALL THE
BLUE JEANS WE TESTED ALL THE
GENES THAT THE NETWORK
PRODETECTION ANTIBODIED SHOULD
BE BASED ON PHENOTYPE ON WHAT WE
OBSERVED AND WE FOUND THAT
ACTUALLY MORE OFTEN THAN IN OUR
ORIGINAL SCREEN, THESE NETWORK
PREDICTIVE CONNECTOR GENES WERE
ALSO KEY REGULATES OF THE MELANO
GHASTER.
SO WE HAVE A LOT INFORMATION
ABOUT A LOT OF GENES, EVERYBODY
CAN SEE THIS, IS THERE A WAY WE
CAN IDENTIFY IF THERE ARE SOME
OF THESE GENES WHOSE ACTIVITY IS
DIFFERENT EVOLVED TO BE
DIFFERENT BETWEEN SPECIES THAT
MIGHT SMAIN TO US WHY THESE
SPECIES END UP WITH DIFFERENT
OVARIOLE NUMBERS.
HERE'S AN EXAMPLE OF A STUDY WE
DID.
FOR REASONS WE SUSPECTED THAT
INSULIN SIGNALING WAS VERY
IMPORTANT TO REGULATE OVARIOLE
NUMBER IN DROSOPHILA MELANO
GHASTER YOU CAN RAISE THOSE WITH
GAIN OF FUNCTION MUTATIONS AND
YOU AM GET MORE EGGS AND YOU CAN
LOWER OVARIOLE NUMBER BY
DEPRESSING INSULIN SIGNALING AND
KEPT FEWER OVARIOLE AND FEWER
EGGS, SINCE WE KNEW THAT THEY
HAD FEWER IN MELANO GHASTER WE
ASKED IF THERE WAS A SYSTEMIC
EVOLVED DIFFERENCE IN THE LEVEL
OF THE SIGNIFY SIGNAL NOTHING
THE OVARY OF DROSOPHILA MELANO
GHASTER VERSES SHELLIA IN THE
KEY TIME IN MARVEL DEVELOPMENT
WHEN THEY'RE MAKING THE OVARIOLE
NUMBER, WE FOUND THE ANSWER WAS
YES, WE'RE HERE'S 1 WAY WE WANT
TO LOOK AT THAT AND INSULIN
BETWEEN 2 SPECIES WE KNOW HAVE
DIFFERENT TRAITS AND 1 WHY DEE
THIS WAS TO QUANTIFY THE
PHOSPHORALATED AKT, WHICH IS A
DROWN STREAM EFFECTOR OF INSULIN
ANIMALS AND PHOSPHORALATED AKT
WHICH IS A PROXY FOR INSULIN
SIGNALING LEVELS OR HIGHER IN
MELANO GHASTER WITH MORE
OVARIOLE THAN THEY WERE IN
SHELLIA WITH LOWER VARIABLES AND
THROUGH A NUMBER OF OTHER
EXPERIMENTS I SHOWED HERE, WE
FOUND EVIDENCE THAT THE
DROSOPHILA SHELLIA INSULIN
RECEPTOR ALLELE HAS EVOLVED A
LIFE ON EARTHER LEVEL OF
ACTIVITY COMPARED TO THE MELANO
GHASTER AND THAT IN PART
ACCOUNTS FOR THE SHELLIA LOWER
NUMBER THAT'S ALSO EVOLVED IN
THE LYE 3 AREAS.
SO FOR THE LAST BIT OF THE TALK
I WANT TO TURN TO SOME OF THE
WAYS WE'RE CONSIDERING
ENVIRONMENTAL REGULATION OF THIS
TRAIT.
I TALKED A LOT ABOUT GENES AND
GENETIC CONTROL OF CELL BEHAVIOR
AND IMPLIED IT'S VERY HERITABLE
TRAIT AND INDEED IT IS, THAT
DOESN'T MEAN IT'S COMPLETELY PIM
PERVIOUS TO ENVIRONMENTAL
REGULATION, LET ME SHOW YOU AN
EXAMPLE OF WHAT I MEAN.
WE KNOW FROM A WORK OF DIFFERENT
MEDIATORS THAT SAEVERRATION HAS
A BIG IMPACT ON NUMBERS, IF YOU
STARVE FRUIT FLIES, THEY HAVE
FEWER OVARIOLE, ANYONE WHO
STAEVER YOUR ANIMALS THEY ARE
GOING TO BE SMALLER, THEY'RE
GOING TO HAVE LESS CELLS, TOTAL
AND THE CELLS THEY DO HAVE ARE
PROBABLY GOING TO BE PHYSICALLY
SMALLER AND WE DID MEASUREMENTS
AND CELL NUMBERS AND CELL SIZE
AND THE STAEVERRED MELANO
GHASTER FLIES HAD FEWER SMALLER
CELLS IN TOTAL INCLUDING
FILAMENT CELLS AND THAT'S WHAT
EXPLAINS WHERE THEY GET FEWER
OVARIOLE WHEN YOU STARVE THEM.
NOW WE ALSO NOTICED THAT AND
THIS STARVATION EFFECT, BY THE
WAY, APPLY TOTION ALL THE
SPECIES THAT WE STUDIED.
SO STARVE MELANO GHASTER, FEWER
OVARIOLE IN NUMBER.
HERE'S THE INTERESTING THING WE
NOTICED.
THE DEGREE OF REDUCTION IN
OVARIOLE IS MUCH GREATER IN
MELANO GHASTER THAN IT IS IN
SHELLIA, AND HERE WHAT YOU'RE
SEEING, THE MELANO GHASTER AND
THE RED BARS ARE THESE 2 SPECS
MELANO GHASTER ON THE RIGHT AND
SHELLY ON THE RIGHT, THE
OVARIOLE NUMBERS ON THE Y-AXIS
MEN WITH HIGHER YOU STARVE THEM.
SO WHEN YOU STAEVER THE MELANO
GHASTER, THE RIGHT PAIR OF BARS,
THE FLIES GET 20% FEWER
OVARIOLES IS WHAT THEY END UP
WITH WITH, WHEN YOU STARVE
SHELLIA, THEY END UP WITH 10%
FEWER OVARIOLES, I TOLD YOU WE
HAVE EVIDENCE THAT INSULIN
SIGNALING SYSTEMICALLY IS
OPERATING AT A LOWER LEVEL AND
WE SUSPECTED THAT PERHAPS
BECAUSE THIS KEY NUTRIENT
SENSING PATHWAY IS OPERATING AT
A LOWER LEVEL, DROSOPHILA
SHELLIA IS LESS ABLE OR LESS APT
TO DETECT CHANGES IN NUCLEOTIDES
THRIGZ WHEN WE SUBJECT IT TO
STARVATION AND THE RESULT THAT
IT NOTICES THAT IT'S BEING
STARVED, THE OVARIOLE DROPS
ACCORDINGLY BUT NOT AS MUCH AS
MELANO GHASTER, IF THIS IS THE
CASE WE MIGHT EXPECT THAT
DIFFERENT POPULATIONS, WHERE
THEY'RE LIVING, WHERE THEY'RE
ENDEMIC TOO, THEY MIGHT DISPLAY
LOWER DEGREES OF ENVIRONMENTAL
OR POPULATION LEVEL VARIATION IN
THE OVARIOLE NUMBER COMPARED TO
MELANO GHASTER THAT WE
HYPOTHESIZE THAT DIFFERENT
POPULATIONS OF MELANO GHASTER
FROM AROUND THE WORLD BECAUSE OF
HIGHER LEVELS OF INSULIN
SIGNALING AND THE GREATER
ABILITY TO DETECT NUTRITIONAL
CHANGES WE MIGHT OBSERVE A
GREATER VARIANCE IN THE NUMBER
WHEN WE COMPARE DIFFERENT
POPULATIONS IN THE MELANO
GHASTER FROM AROUND THE WORLD.
SO ANDRE GOT HIS HANDS ON A
BUNCH OF POPULATIONS OF MELANO
GHASTER FROM AROUND THE WORLD
AND A BUNCH OF DIFFERENT
POPULATIONS FROM AROUND THE
SHELLS, HE COMPARED THE OVARIOLE
NUMBER AND THE KEY THING WE'RE
ASKING ABOUT HERE IS THE
VARIANTS.
AND WE FOUND THAT OUR PREDICTION
WAS SUPPORTED BY THE DATA WE
GATHERED.
SO THE BLACK SYMBOLS, WHITE AND
BLACK, ARE THE OVALID AND
RELIABLEIOLE NUMBERS ON THE
Y-AXIS OF DIFFERENT DROSOPHILA
POPULATIONS.
AND THE RED SIM BOOM BOOM SYMBOLS ARE MU CH
SMALLER THAN THE MELANO GHASTER
VARIANT.
SO BECAUSE THE MOLECULAR
MECHANISM IS THE SAME FOR FRUIT
FLIES NUTRIENT SENSING AND FOR
HERITABLE CHANGE IN OVARIOLE
NUMBER, THIS EVOLVED DIFFERENCE
IN THIS KEY NUTRIENT SENSING
SIGNALING PATHWAY MIGHT EXPLAIN
NOT JUST SPECIES SPECIFIC
DIFFERENCES IN OVARIOLE NUMBER
BUT SPECIES SPECIFIC TO
PLASTICITY IN OVARIOLE NUMBER
WHICH IS WHAT WE'RE SEEING IN
THESE POPULATIONS.
ALL RIGHT, TO END UP THIS TALK,
I WANT TO TELL YOU ABOUT SOME OF
THE WORK WE'RE DOING IN HAWAII
AND HOW THIS IS HELPING US THINK
ABOUT THIS PROBLEM.
WE'VE LOOKED AT A RANGE OF
OVARIOLE NUMBERS FROM SOMETHING
LIKE 10-20 PER OVARIOLE BY DO
EGULATION--REGULATORY THESE
COMPARISONS RIGHT AND THAT'S AS
PITCHER AS WE CAN PUSH IT IN
THIS GROUP OF DWELVE DROSOPHILA
SPECIES AND I SHOWED AT THE
BEGINNING THESE ARE JUST THE 12
WHOSE GENOMES WERE FIRSTYQUENCED
AND MADE PUBLICLY AVAILABLE.
THERE ARE ABOUT 4000 DESCRIBED
SPECIES WORLD WIDE, ABOUT A
THOUSAND OF THEM EVOLVED ONLY
ABOUT TWEBT MILLION YEARS AGO,
ON THE HAWAIIAN ISLANDS.
THIS GROUP, DROSOPHILA ABOUT A
QUARTER WORLD WIDE OF DIVERSITY,
IT IS INCREDIBLY VARIABLE IN
TOMPLES OF ALL SORTS OF
MORPHOLOGICAL TRAITS ASK
INCLUDING A NUMBER, AND MUCH
3000 DROSOPHILA SPECIES FROM THE
REST OF THE WORLD.
THE KONT NEBT AT VARIABLE NUMBER
RANGE AS WE TALKED ABOUT IS SORT
OF BETWEEN 10 AND 20 VARIABLE,
BUT IN HAWAII CAN YOU FIND THE
SPECS WITH 1 OR 2 OVARIOLES OR
ALMOST A HUNDRED OVARIOLE IN
THEIR OVARIES SO WE'RE
INTERESTED IN UNDERSTANDING THE
GENLETTIC AND ECOLOGICAL BASIS
OF THIS HUGE VARIATION IN THIS
GROUP OF SPECIES THAT UNDERWENT
AN EXPLOSIVE ISLAND IN THE
RADIATION AND A VERY SHORT
PERIOD OF TIME.
SO TO DO THIS WORK, IT INVOLVES
FIELD WORK, IT'S NOT VERY
GLAMOROUS AND YOU'RE LITERALLY
SITTING ON THE FOREST FLOOR IN A
RAIN FOREST DIGGING THROUGH MUD
AND LOOKING FOR MAGGOTS BUT IT'S
NOT AMAZING, BUT THE INSIGHTS WE
HOPE IT WILL BE AMAZING WE GO TO
HAWAII, WE DENTIFY THE KEY
FORESTS FILLED WITH INDEMMIC
HAWAIIAN PLANTS BECAUSE AS YOU
WILL SEE THESE HAWAIIAN
DROSOPHILA HAVE SPECIFIC
ASSOCIATIONS WITH SPECIFIC TYPES
OF PLANTS THAT ARE ALSO ENDEMIC
TO THE HAWAIIAN ISLANDS.
IF YOU FIND MAGGOTS YOU MIGHT
GET LUCKY BUT MORE OFTEN WE
CATCH ADULTS AND LITERALLY HAVE
TO HAND CATCH THEM 1 BY 1 WITH A
SERIES OF DIFFERENT SNEAKY
TRICKS AND TRAPS AND SOME OF
THESE SPECIES ARE AICIAL TO COME
BACK TO THE LAB AND LIVE WITH
US.
AND I WANT TO SAY WE COULD NEVER
HAVE ACCOMPLISHED WITH WITH OUT
OUR COLLABORATORS IN HAWAII
[LISTING NAMES ] SEE US THE
PLANTS AND HELP US WREER THE
FLIES AND I NEED TO THANK THEM
AS WELL.
SO I ALREADY SAID THE HAWAII
KNOW DROSOPHILA MAKE UP A WORLD
WIDE POPULATION OF THESE, WE
KNOW AND OTHERS BEFORE US HAVE
LOOKED AT THIS, THE APPROXIMATE
ORIGIN IN TIME AND IN SPACE OF
THESE DIFFERENT LINEAGES SORT OF
WHO ORIGINATED WHERE AND THE
SHORT VERSION OF THE STORY IS
THAT MANY LINEAGES ROSE ON MANY
INDEPENDENTLY AND THERE ARE MANY
LINEAGES THAT DRAFUL BACK AND
FORTH BETWEEN ISLANDS.
OKAY?
I MENTIONED ALREADY THAT THE
HAWAIIAN DROSOPHILA HAVE
SPECIFIC PRESCRIBING FERENCES
FOR INDEMMIC HAWAIIAN PLANTS.
SOPHISTICATEDY THERE ARE SOME OF
THEM ARE MUCH MORE SPECIALIZED
THAN OTHERS, SOME OF THEM WILL
ONLY LAY THEIR EGGS ON CERTAIN
FRUITS OR CERTAIN FUNNING I OR
IN THE SPIDER CO COONS OF A
SPECIFIC ENDEMIC SPIDER SPECS IN
HAWAII SOME OF THEM ARE MORE
SPECIFIC AND SOME OF THEM ARE
MORE GENERALIZED, SOME LAY THEM
IN THE BARK, AND WHERE THEY LAY
THE EGGS, THAT'S WHERE THEY WILL
HATCH AND WHERE WHERE THEY HARCH
THEY WILL EAT AND AS UF SEEN
THERE'S PLASTICITY AVAILABLE TO
CONTRIBUTE TO EVOLUTION IN THIS
SYSTEM.
AND SO, WHAT YOU ARE SEEING HERE
IS A TREE OF A NUMBER OF
DIFFERENT HAWAIIAN DROSOPHILA
SPECIES, THEY FALL INTO 5 MAJOR
GROUPS WHICH YOU CAN SEE IN
THESE LITTLE VERTICAL CLAIFS
HERE, THIS IS THE KACCT TININE
PATHWAYA MYSELFA, WHICH IS ALL
THE REST OF THE GROUP, THE
MORPHED PARTS AND THE
HOLLOACULA, THEY ARE A
UNDERSTUDIED GROUP AND HARD TO
CATCH.
WE HAVE THE SO CALLED AMC GROUP
AND THE AMC AND THE MMs, YOU
CAN SAY THEY REALLY LIKE THESE
GREEN SUBSTRATES, THEY EVOLVED
THROUGH SPECIALIZATIONOT LEAVES
OF SPRVEG HAWAIIAN PLANTS.
AND THEN WE HAVE THE P NA CLAYED
KNOWN AS THE PICTURE WINING
CLAYED AND THEY ARE OFTEN BARK
BREEDERS WITH A FEW DIFFERENT
VARIATIONS AND THE CIRCLES ON
THESE, ON THE LITTLE DIFFERENT
NODES AND LINES OF THIS TREE
INDICATE PLACES WHERE THIS
ANALYSIS SUGGEST THAT THERE HAVE
BEEN EVOLUTIONARY SHIFTS IN MOST
PREFERENCE, SO ALL OF A SUDDEN A
LINEAGE WILL EVOLVE WITH
DIFFERENT PREFERENCE FOR A
SUBSTRATE TO LAY THEIR EGGS TO
WITHIN ANCESTORS SO WITH ALL OF
THIS INFORMATION COMBINED, WE
HAVE A BIT OF INFORMATION ABOUT
THE EVOLUTIONARY RELATIONSHIPS
OF THE CLIENTS WHERE THEY LIVE,
THE OVARIOLE NUMBERS, SUBSTRATE
REFERENCES, ULTIMATELY LAWN
MOWER I WOULD LOVE TO GET AT ARE
WHAT ARE THE EVOLUTIONARY
DIFFERENCES IN GENE EXPRESSION
AND FUNCTION BETWEEN THESE
DIFFERENT LINEAGES THAT CAN HELP
US EXPLAIN THE EVOLUTION OF
DIFFERENT GENETIC CONTROL OF
THESE VARIABLE TRAITSER, HERE
WE'RE TALKING ABOUT OVARIOLE.
NOW I MIGHT SAY, OKAY, LYOU KNOW
ABOUT THE GENES IN MELANO
GHASTER WHY DON'T YOU SEQUENCE
THIS TRANSCRIPTOME OR SOMETHING
OF THESE HAWAIIAN OVARIOLES AND
THEN COMPARE THEM AND EXPRESS
DIFFERENTLY THOSE ARE THE JEERNS
THAT WILL BE IMPORTANT AND THAT
IS ABSOLUTELY A GREAT APPROACH,
HOWEVER, 1 THING WE HAVE TO
THINK ABOUT IS OKAY, WE WILL
SEQUENCE LET'S SAY THE
TRANSCRIPT ORDER OF MICRONSS,
GENOMES WHATEVER YOU FEEL LIKE
SEQUENCING, BETWEEN THESE
DIFFERENT SPECIES AND YOU WILL
SAY, - BEING IF I SEE
DIFFERENCES, MAYBE THOSE ARE THE
DIFFERENCES THAT ARE RESPONSIBLE
FOR THE TRAIT DIFFERENCE BETWEEN
THE SPECIES.
HERE'S THE THING, YOU KNOW
THERE'S GOING TO BE DRVESS, THE
DIFFERENCE SPECIES, ARE
DIFFERENT EVOLVING ABOUT LAWN
MOWER'S LONG AND SHORT BUT WE
EXPECT THEM TO BE DIFFERENT,
RADIOIT?
I WAS SAYING EARLIER TO SUSAN,
WHY DON'T I HAVE ELEPHANT'S
TRUNK, WELL I'M NOT AN ELEPHANT
WORKERS SHARE A COMMON ANCESTOR
A WHILE AGO, SO WE EVOLVE TO BE
DIFFERENT.
OUR QUESTION IS HOW CAN WE TELL
WHICH DIFFERENCES ARE GREATER
THAN THOSE WE WOULD EXPECT TO
OCCUR JUST BECAUSE THESE
LINEAGES HAVE BEEN DIVERGING,
WHICH OF THESE DIFFERENCES WE
SHOULD BE PAYING ATTENTION TO
BECAUSE THEY MIGHT EXPLAIN THIS
ADAPTIVE EVOLUTION OF DIFFERENT
OVARIOLE.
SO I WANT TO TAKE YOU JUST FOR A
COUPLE OF MINUTES THROUGH A
THOUGHT EXERCISE TO ILLUSTRATE
THE COMPLEXITY OF THIS PROBLEM.
LET'S SAY YOU'RE JUST DOG A 3
SPECIES COMPARISON AND HAVE YOU
3 SPECIES OF YOUR FAVORITE
INSECTS HERE AND COMPARING THE
TIMING OF GENE EXPRESSION AND
YOU FIND THAT IN 2 SPECIES, YOUR
GENE THAT YOU LIKE IS EXPRESSED
AT 1 STAGE, AND AT THE OTHER
SPECIES IT'S EXPRESSED AT A
DIFFERENT STAGE, YOU MIGHT SAY
WELL, BY SORT OF STRICT
PARSIMONY, I HAVE 2 SPECIES
EXPRESSING AT STAGE 1 AND 1 AT
STAGE 2 AND ALSO, 1 OF MY
SPECIES THAT EXPRESSES AT STAGE
1 IS THE OUTGROUP TO THE OTHER 2
SPECIES BY STRICT PARSE MONEY, I
WILL HAVE TO HYPOTHESIZE THAT
THE GRAY EXPRESSION STAGE AND
STAGE 1 IS THE ANCESTRAL STATE
AND THE BLUE IS THE DERIVED
STATE, YOU SAY THERE IS
REASONABLE, I HAVE READ LOTS OF
PAPERS INCLUDING OUR OWN THAT
MAKE THIS SORT OF INFERENCE.
OKAY, HERE'S THE THING, WHEN WE
THINK ABOUT THE EVOLUTIONARY
PROCESS WE HAVE TO ADMIT THAT
THINGS COULD BE MORE
COMPLICATED.
BECAUSE WE KNOW THAT THERE ARE
NOT JUST 3 INSECTS IN THE WORLD
NOR--A MILLION INSECTS THAT ARE
DESCRIBED THAT WE KNOW ARE ALIVE
TODAY AND COLLECTIVELY, THE
COURSE OF EVOLUTION OF THESE
INSECTS SPANS LITERALLY BILLIONS
OF YEARS OF EVOLUTIONARY TIME.
SO THERE HAVE BEEN BILLIONS OF
OPPORTUNITIES TO MAKE
EVOLUTIONARY CHANGE.
NONAPOPTOTIC YOU YOU COULD SAY,
WELL, IN MY VERY LIMITED TAXON
SAMPLING, I SAMPLED 3 SPECIES
OUT OF A MILLION LIVING SPECIES,
MAYBE THERE WAS ONLY 1
EVOLUTIONARY CHANGE IN THIS
STRAIGHT, THE BLUEAR O AND I
HAPPEN TO CATCH IT BY CHANCE,
THAT COULD BE.
BUT IT'S--IT SEEMS A LITTLE LESS
LIKELY, THERE WASN'T ONLY 1
CHANGE BUT YOU HAPPEN TO CATCH 1
OF THE CHARGES AND HOW MANY
CHAIMPLES ARE THERE AND HOW CAN
WE KNOW WHEN WE'RE ONLY SAMPLING
A VERY SMALL AMOUNT OF THE
LIVING VARIATION?
WE CAN'T OBSERVE THE PREVIOUS
VARIATION AND WE KNOW WE HAVEN'T
OBSERVED ALL THE LIVING
VARIATION, SOPHISTICATEDY I
MOOIT SAY WELL, THIS TRAIT
CHANGES QUICKLY OVER
EVOLUTIONARY TIME, THERE WERE
NOT THAT MANY CHANGES, THERE
WERE MORE THAN 1 BUT I
DEPARTMENT THINK THERE WERE THAT
MANY AND I DID GET LUCK SKPE
BAKUGAN I SASM ED 1 OF THE FEW
THERE ARE.
BUT WHAT IF THIS TRAIT CHANGES
VERY QUICKLY OVER EVOLUTIONARY
TIME WHARKS IF IT'S CONTRIBUTED
TO BY 300 GENES ALL OF WHICH ARE
POTENTIAL TARGET FOR THE CHANGE.
SO YOU MY EXPECT A GREAT DEGREE
OF THIS RANGE WHAT IF IT'S HIGH
IN THE ORGANISM OR HIGH IN THE
HOT SPOTS OF THE GENOME OF THE
GENES YOU CARE ABOUT, NOW YOU
THINK, CAN I BE CONFIDENT THAT
THE BLUE STATE REALLY IS A
DERIVED STATE AND NOT ANN
CESTERAL STATE?
AND OF COURSE WE ALSO KNOW WE
KNOW SO LITTLE OF THESE EVENTS
THAT WE HAVE TO BE HONEST AND
EXCLUDE THE POSSIBILITY THAT WE
CAN'T SAY ANYTHING WITH WE DO A
TAXON SAMPLING OF 3.
OKAY CROSS LINKING SO HOW WE
GOING TO DEAL WITH THIS?
HERE'S HOW WE'RE THINK BEING IT
IN THE LAST COUPLE OF SLIDES,
SAM 20 TO HAWAII, COLLECTED
DWELVE SPECIES IN THE GRAY BOXES
OVER HERE, AND SAMPLED 12FUL
THEM HERE IN THE CYAN THINGS FOR
EXPRESSION OF ANALYSIS.
THESE WILD CAUGHT ANIMALS HE
CREATED SORT OF BULK SEQ RNA
TRANSCRIPT OHMS OF THE THEIR
HEADS BECAUSE WE'RE INTERESTED
IN NERVOUS SYSTEM FUNCTIONS FOR
BEHAVIORAL REASONS OF THE
OVARIOLES AND THE REST OF THE
CARCUS, AND FROM A WHOLE
INDIVIDUAL FROM EACH SPECIES AND
THESE ARE INDIVIDUAL RNAI CROSS
LINKING SO THEY'RE SEQUENCES
FROM 1 OVARY TO FROM 1 HAND, ET
CETERA PERSPECIES, IN TRIPLICATE
AND TECHNICAL TRIPLICATE AND
BIOLOGICAL TRIPLICATE.
AND WHAT ARE WE ASKING IS WHAT
ARE EXPRESSION DRCHS BETWEEN THE
FOCUS ON THE OVARY BETWEEN THE
DIFFERENT SPECIES, WE KNOW
THERE'S DIFFERENCES BUT WHAT ARE
THE DIFFERENCES WE SHOULD FOCUS
ON?
HERE'S A PLOT OF THE SORT OF
EXPRESSION BIAS SO ON THE RIGHT
ARE GENES THAT HAVE HIGHER
EXPRESSION IN THE OVARY THAN IN
THE REST OF THE BODY.
ON THE LEFT ARE GENES THAT HAVE
HIGHER EXPRESSION IN THE WHOLE
REST OF THE BODY AND RATHER THAN
THE OVARY AND WE ASKED WHICH OF
THESE ARE KNOWN TO BE HIGHLY
EXPRESS INDEED THE DROSOPHILA
MELANO GHASTER AVARY BECAUSE
THOSE ARE LIKELY TO BE
FUNCTIONAL IN THE OVALID AND
RELIABLE SKPE BAKUGAN ARE THERE
POTENTIALLY OVARY BIASED GENES
THAT HAVE EVOLVED DIFFERENT
DEGREES OF BIAS IN DIFFERENT
LINEAGES OF THE HAWAIIAN FLIES.
OKAY, WE ALREADY KNOW AND THIS
PLOT IS SHOWING YOU LOTS OF
EVOLVED CHANGES IN THE
EXPRESSION AND EVEN JUST IN THIS
STORY.
NOW WE CAN SAY OKAY ARE THERE
YEENS THAT HAVE EVOLVED IN OVARY
BIASED EXPRESSION RELATIVE TO
SOME OF THEIR NEIGHBORS OR SOME
OF THERE ARE COUSINS.
WE KNOW THE EVOLUTIONARY REAPS
BETWEEN THESE FLIES AND THIS IS
A CRITICAL PREREQUISITE FOR THIS
ANALYSIS AND THEN WE CAN SAY
OKAY, IN THIS SPECIES NOT ONLY
IS THIS BIASED TOWARDS THE
EXPRESSION IN THE ASLARY, MORE
IN THE OVARY THAN THE REST OF
THE BODY BUT IT EVOLVED THAT
NEWEL FREE RADICALS ANN CESTOR
THAT DIDN'T HAVE THE BIAS, THOSE
ARE THE RED DOTS WE CAN ASK THE
OTHER QUESTIONS WHICH ARE GENES
THAT DIDN'T USED TO BE BIAS AND
EXPRESSION IN THE REST OF THE
BODY AND THE NONOVARY, BUT THEN
THEY EVOLVE THAT CARCUS BI AS
AND THOSE ARE THE BLUE DOTS AND
SO O. SO AGAIN WE HAVE LOTS OF
CHANGES.
WE CAN PINPOINT THE SORT OF
EVOLUTIONARY DIRECTION OF SOME
OF THESE CHANGES BUT WHICH 1S OF
THESE CHANGE SAYS ARE KIND OF
UNUSUALLY LARGE OR UNUSUALLY
INTERESTING TO US FOR THE BACK
DROP OF LINEAGE DIVERSIFICATION
THAT IS ALREADY HAPPENING AND WE
ASK ASK A COUPLE OF QUESTIONS
AND ARE THERE A GROUP OF GENES
THAT EVOLVE IN A LARGE CHAIN AND
EXPRESSION BIAS, THOSE MIGHT BE
INTERESTING CANDIGATES RELATIVE
TO THE WHOLE TRANSCRIPTIONAL
ACTIVITY BACKGROUND OF THE FLY.
AND OTHER - QUESTION RELATED IS
WE CAN ASK WHETHER GROUPS OF
GENES WHO WHOSE EXPRESSION
EVOLVES IN THE SAME DIRECTION,
WE ALL EVOLVE IN OVARY BIAS,
MAYBE THESE ARE CHARGES AGAIN
THAT INVOLVE AN OVARY BIAS
TOGETHER IN PARTICULAR LINEAGES
BUT NOT AS A SIMPLE CONSEQUENCE
OF THE EVOLUTIONARY
DIVERSIFICATION OF THESE
LINEAGES.
THESE MIGHT BEING CHANGES WE'RE
INTERESTED IN AND SO SAM
DEVELOPED A COUPLE OF METHODS TO
ASK THESE 2 DIFFERENT 83S, IN
THIS PLOT HERE WHAT ARE WE'RE
DOING IS COMPARING, WE'RE
BASICALLY ASKING HOW MUCH OF THE
VARIATION IN OVARY BIASED
EXPRESSION, SNOW MUCH OF THAT
DIFFERENT EXPRESSION APPEARS TO
BE ATTRIBUTABLE TO JUST THE
EVOLUTIONARY DISTANCE BETWEEN
THE LINEAGES WHICH IS ON THE
X-AXIS?
AND HOW MUCH IT MIGHT BE DUE NOT
TO THERE'S BEEN A LOT OF
DISCIPLINARY VERSIFICATION
BETWEEN THE LIGANS BUT A LOT OF
CHANGE BETWEEN THE ORGANS WHICH
WE ASK THE QUESTION THAT WAY, IT
HELPS US SEE WHAT SHOULD BE THE
NEXT STEPS WE SHOULD TAKE IN
THIS ANALYSIS.
WE SHOULD CHOOSE FOR EXAMPLE,
GENES THAT HAVE EVOLVE INDEED
VERY DIFFERENT DEGREE OF OVARY
BIAS IN FLIES FROM CLAYEDS A AND
B SORRY EXAMPLE BECAUSE THEIR
OVARY EXPRESSION IS MORE
DIFFERENT THAN WE WOULD EXPECT
GIVEN HOW CLOSELY RELATED THERE
A ARE, CHOOSING IF ARE EXAMPLE,
TO COMPARE A SPECIES FROM GROUP
A WITH A SPECIES FROM GROUP D
AND SAYING WHOA, I FOUND SOME
GENES THAT ARE REALLY
DIFFERENTLY EXPRESSED FROM THE
OVARIES FROM SPECIES A AND D AND
THAT MIGHT BE A GREAT CLOIS
BECAUSE WE EXPECT THEM TO BE
DIFFERENT IN THEIR DEGREE OF
BIAS GIVEN THE AMOUNT OF
DIVERSIFICATION THAT'S HAPPENING
BETWEEN THESE LINEAGES AND
FINALLY ANOTHER WAY WE CAN THINK
ABOUT THIS PROBLEM IS TO
LEVERAGE INFORMATION FROM
DROSOPHILA MELANO GHASTER, WHERE
EVERY GENETIC INTERACTION HAS
BEEN KNOWN TO REACT.
AND WE KNOW IF THESE INTERACT IN
FUNCTIONALLY RELEVANT WAYS LIKE
PROTEINSOT PLOT, OR GENETIC
INTERACTIONS OF ENHANCEMENT OR
SUPPRESSION OF THE RIGHT HAND
PLOT AND WE CAN ASK WHETHER
GENES THAT IN THE MELANO GHASTER
INTERACT IN THESE KNOWN WAYS ARE
MORE LIKELY TO EVOLVE CONCERTED
OVARY BIAS OR LOSS OF OVARY BIAS
IN THE HAWAIIAN DROSOPHILA AND
INDEED WE FIND THAT GENES THAT
EVOLVE SIMILAR BIASED EXPRESSION
IN THIS ORGAN OR THAT ORGAN WE
CARE FOR THE OVARY HERE, THEY DO
TEND TO HAVE SOME SORT OF
FUNCTIONAL RELATIONSHIP WITH
EACH OTHER WHETHER GENETIC OR
PHYSICAL.
SO THESE TYPES OF APPROACHES OF
THESE COMPARATIVE TRANSCRIPTOMES
THAT WE HAVE DMOW, GIVE US NEW
TESTABLE GENE REGULATORY
HYPOTHESIS THAT WE CAN GO IN AND
INVESTIGATE AND SPECIFIC SORT OF
LOGICALLY SELECTED HAWAIIAN
SPECIES THAT HELP US UNDERSTAND
AND EXPLAIN THE LINEAGE
DIVERSIFICATION OF THE OVARIOLE
NUMBER THAT MAY HAVE BEEN
ADAPTED ON THE DIFFERENT
SUBSTRATES THAT THEY EVOLVE
THEIR RELATIONSHIPS WITH.
AND FINALLY I WANT TO LEAVE YOU
HAVING SPENT SO MUCH TIME ON
MELANO GHASTER, ON DROSOPHILA
AND LET'S SOMATIC CELLUTE AND
CONSIDER ALL INSECTS AND WE SAID
THAT IN THE DROSOPHILA, WE HAVE
A RANGE OF NUMBERS OF 1 TO A
HUNDRED, GIVE OR TAKE THAT
NUMBER IS VERY STRONGLY
CORRELATED WITH EGG LAYING, IT
TURNS OUT NEITHER OF THOSE ARE
TRUE IF WE ZOOM OUT AND LOOK
ACROSS ALL THE SIN SECTIONAL
ANALYSISS SO WHAT THEY DID WAS
LOOK THROUGH COUPLE THOUSAND
DIFFERENT PAPERS FROM THE
LITERATURE THAT OTHER PEOPLE
HAVE COUNTED OVARIOLE NEAR US SO
WE DON'T HAVE TO COUNT ALL THE
OVARIOLE NOBS IN THE WORLD WE
CAN LOOK AT WHAT OTHER VS DONE
AND WE CAN PLOT THE NUMBER ON
THE X-AXIS HERE AND WE HERE
WE'RE YOU GROUPING ON THE Y-AXIS
DIFFERENT MAJOR GROUPS OF
INSECTS THE COLORS ARE DIFFERENT
SO WE CAN DEVELOPMENTAL
ENDOCRINOLOGY REBTIATE THEM FROM
EACH OTHER AND THEY ARE INSECTS
THAT HAVE ONLY 1 OVALID AND
RELIABLEIOLE IN THE WHOLE BODY,
THIS MEANS THEY DO NOT HAVE A
BILATERALLY SYMMETRICAL 1 AND
THAT INSECTS THAT HAVE 10,000
OVALID AND RELIABLEIOLES IN
THEIR BODY, THESE ARE TEND TO BE
THE SOCIAL INSECTS LIKE ANT
QUEEN EXPWS SO O. STILL THOUGH
IF IF WE DESCRIBE THE SHOASH
INSECTS WHICH HAVE THEIR OWN
THING GOING ON, WE HAVE BEATLESS
THAT HAVE OVER A THOUSAND
OVARIOLE IN AN AVARY SO A
MISCELLANEOUSIVE AMOUNT OF
VARIATION, I DON'T KNOW ABOUT
THE TOURNAMENT FILAMENT ITSELF,
NUMBER OR BEHAVIOR CAN EXPLAIN
ALL OF THIS VARIATION, RIGHT?
EVEN MORE CRAZY TO ME, IS THE
FACT THAT WE OBSERVE REPEATEDLY,
GROUPS OF INSECTS THAT HAVE
EVOLVED AN INVARIANT NUMBER, IF
YOU REMEMBER THE COMPARISON
WHERE WE LOOKED AT THE DEGREE OF
VALID AND RELIABLE YABTS IN THE
POPULATIONS AROUND THE WORLD SO
DIFFERENCES OF SHE'LLIA
POPULATIONS FROM THE SHELLS AND
I TOLD YOU, I KEPT SAYING
OOVARIOLE NUMBER MEAN OVARIOLE
NUMBER, THERE'S A SPECIES
SPECIFIC NUMBER IN DROSOPHILA IN
ALL DROSOPHILA SPECIES THAT WE
LOOKED AT.
IF YOU DISSECT A HUNDRED FLIES
THEY DON'T HAVE EXACTLY 10
OVALID AND RELIABLEIOLES THEY
HAVE 10, PLUS OR MINUS 2
DEPENDING ON THE SPECIES.
HOWEVER, CAN YOU SEE THEM IN
THESE VETERINARY RESOURCES
CALIFORNIA LINES THAT POP UP
HERE AND THERE TOWARDS THE
LEFT-HAND SIDE OF THIS PLOT,
THESE ARE INSECTS THAT HAVE
INVARIANT NUMBER AND YOU CAN
SIGNIFY SECTIONAL ANALYSIS A
HUNDRED AND FIND THE EXAM SAME
NUMBER OF OVARIOLES IN THERE.
I ALSO DON'T THINK THAT THE CELL
BIOLOGICAL AND MORPH O GENETIC
PROGRAMS THAT WE DISCOVERED ARE
IMPORTANT FOR OVARIOLE MORPH O
GENESIS AND DETERMINATION IN
MELANO GHASTER, I THINK THEY CAN
EXPLAIN HOW YOU ALWAYS GET THE
SAME NUMBER OF OVARIOLES EVERY
TIME AND YET THIS IS A COMMON
OCCURRENCE THAT'S EVOLVED MANY
DIFFERENT TIMES IN THE INSECTS.
SO GOING FORWARD ANOTHER
DIRECTION I WOULD LOVE TO GO IN
WE HAVE THOUSANDS OR THEY HAVE
EXACTLY THE SAME NUMBER OF
OVARIOLES EVERY TIME AND ASK
WHAT THE DEVELOPMENT AT BASIS OF
THAT BEHAVIOR IS.
AND FROM THERE WE CAN DISCOVER
THE DIFFERENT GENETIC BASIS FOR
CONTROLLING DIFFERENT OVARIOLES
IN THESE DIFFERENT LINEAGES.
ALL RIGHT, SO TO WRAP UP, THE
BIG TAKE AWAYS THAT I HAVE FOUND
REALLY USEFUL, OVER THESE YEARS,
FROM THIS APPROACH IS TO
UNDERSTAND THAT THESE COMPLEX
ADULT FITNESS TRAITS CAN
ULTIMATELY THROUGH A
DEVELOPMENTAL BI OMGIST LENS CAN
COME DOWN TO DECISIONS DURING
DEVELOPMENTAL STAGES, THERE'S NO
SINGLE SMOKES GUN GENE OR
REGULATORY PATHWAY THAT CAN
EXPLAIN ALL THE VARIATION IN
THIS TRAIT, LET ALONE REGULATION
IN A SINGLE ORGANISM, IN TERMS
OF CELL-CELL SIGNALING CLEARLY
EXTREMELY IMPORTANT EVERY SINGLE
EVOLVED CONSERVED ACTIVITIES AND
PROJECTS MALSIGNALING PATHWAY
HAS SOME SKIN IN THIS GAME AND
WHEN IT AM CANS TO OVARIOLE IN
THIS PARTICULAR TRAIT WE FOUND
THIS INTERESTING LINK, THE
INSULIN SIGNALING LINK BETWEEN
THE HERITABLE VARIATION AND THE
NUMBER AND THE ENVIRONMENT
REGULATED VERYIATION OF THE
NUMBER AND IT'S QUITE EXCITING
BECAUSE IT'S SORT OF A LONG
STANDING PROBLEM IN EVOLUTIONARY
BIOLOGY TO UNDERSTAND WHETHER OR
NOT NONHERITABLE VARIATION SORT
OF ENVIRONMENTALLY INDUCED
VARIATION IS REEL KEEPSAKES VABT
TO THE PROCESS BECAUSE IF IT'S
INDUCED BY THE VIEMPLET AND
CAN'T BE INHERITED THEN MAYBE
YOU DON'T CARE ABOUT AN
EVOLUTION, BUT IF THAT
PLASTICITY IS MEDIATED BY A
PATHWAY, WHOSE ACTIVITY ITSELF
CAN BE DIFFERENT INHERITABLE
WAYS MAYBE THIS IS A WAY YOU CAN
LINK PLASTICITY TO HERITTITY AND
THEN FINALLY, WE FIND IT REALLY
FRUITFUL TO BEGIN TO THINK MORE
AND MORE ABOUT SORT OF NULL
EXPECTATIONS FOR EVOLUTIONARY
CHANGE.
WE KNOW THERE WILL BE CHANGE BUT
WE WANT TO KNOW HOW MUCH CHANGE
WE COULD EXPECT SO WE CAN KNOW
AND SHOULD BE SURPRISED AND
WHICH LEADS WE SHOULD FOLLOW
NEXT.
SO FINALLY OF COURSE, I NEED TO
THANK ALL OF OUR COLLABORATORS
AND OUR FUNDING SOURCES AND THE
GREAT GROUP OF INTERDISCIPLINARY
SCIENTISTS THAT I WORK WITH IN
THE LAB AND THANK YOU FOR YOUR
ATTENTION AND BEARING WE ME AS
WE HAD A COUPLE OF TECHNICAL
GLITCHES AND I WOULD LOVE TO
TAKE ANY QUESTIONS YOU MIGHT
HAVE.
THANKS.
NTHAT WAS A WONDERFUL TALK,
THANK YOU VERY MUCH I THINK YOU
HAVEN'T SEEN ME BEFORE, I'M
[INDISCERNIBLE] I'M A TENURED
[INDISCERNIBLE] AT NIDDK I HAVE
THE PRIVILEGE TO DO THE Q&A WITH
YOU.
I ALREADY HAVE QUESTIONS BUT FOR
EVERYONE WHO HAS A QUESTION
PLEASE USE THE SEND LIVE
FEEDBACK BUTTON ON THE BOTTOM OF
YOUR SCREEN AND JUST SEND US
YOUR QUESTIONS AND WE WILL ASK
SANDRA, I WOULD ALSO LIKE TO
REPEAT THE CME CODE FOR TODAY
WHICH IS 37934.
327934.
OKAY THANK YOU VERY MUCH CAN I
START AND DO YOU SEE ANY
RELATIONSHIP WITH POPULATION
SIZE.
>> OOH, SO INTERESTING.
EFFECTIVE POPULATION SIZE ARE
PRETTY GARBAGE, BUT TO SORT OF
SPIT BALL THIS, I THINK THAT WE
FIND THAT SPECIES WITH LOWER
EFFECTIVE POPULATION SIZES ARE
GOING TO HAVE LOWER VARIANTS IN
ON OVARIOLE NUMBER.
I DON'T KNOW TAKEN--THEY WE CAN
PREDICT A LOT OF THE ABSOLUTE
OVARIOLE NUMBER OR AMINEE
OVARIOLE BUT THE NUMBER THIS
WILL BE LOWER.
YOU MIGHT GUESS THAT ANYWAY
BECAUSE WE KNOW THAT HIGH
DEGREES OF INVOLVABILITY COME
WITH DIFFERENT POPULATION SIZES
AND WE MIGHT EXPECT LOWER
VARIANTS IN A POPULATION WITH A
LOWER EFFECTIVE POPULATION SIZE.
BUT THAT WOULD BE MY PREDICTION.
THAT WOULD BE MY PREDICTION
BASED ON THE SMALL AMOUNT OF
IMPERICAL DATA WE HAVE, I THINK
THAT MAY BE THE CASE.
>> YEAH, THERE'S 1 QUESTION TBR
SUSAN [INDISCERNIBLE] AND SHE'S
WONDERING ABOUT YOUR
ASSIMMULATED ORGANISM WHICH IS
SUPER COOL AND REALLY WONDERING
ABOUT HOW YOU INTEGRATE THIS IN
YOUR RESEARCH AND HOW DO YOU
CHOOSE THE CHARACTERISTICS?
>> THAT'S SUCHT A GREAT
QUESTION.
SO THE SIMULATED ORGANISM WE
WORKED WITH THE MOST AND THE
CRICKET EMBRYO AND WE WERE DOING
THIS RELATIVELY UNRELATED STUDY
LOOKING AT EARLY CELL MOVEMENT
DECISIONS AND INSECT EMBRYOS SO
THOSE WHO STUDY INSECTS PROBABLY
KNOW THAT THE FIRST DIVISIONS OF
INSECT IMBREAKTHROUGH OS ARE
AREN'T HOLLOW BLASTIC, SO THE
FIRST MITOTIC CLEAVAGE, SKIPPED
CYTOKINESIS AND YOU END UP WITH
1 CELL WITH A LOT OF NUCLEI
INSIDE IT.
BECAUSE THEY REPLICATE IT AND
THEY DIDN'T SEPARATE IT INTO
SEPARATE CELLS SO YOU MAKE THIS
BAG, AND THE NUCLEI WILL HAVE TO
MOVE TO POPULATE THE CORTEX, AND
THEN THEY GET CELL MEMBRANES AND
CELLULARRIZE AND MOW HAVE YOU A
BLASTODERM, JUST LIKE ANY OTHER
ANIMAL EMBRYO REALLY SO HOW DO
WOE GO TO THE RIGHT PLACE,
BECAUSE IF THEY'RE ALL BORN IN
THE MIDDLE OF THE YOLK YOU WILL
NEVER MAKE AN EMBRYO, THEY HAVE
TO--WITH THIS PROBLEM IN A WAY
BIGGER EMBRYO THAT DEVELOPS MUCH
MORE SLOWLY THAT HAS A NICE
TRANSPARENT EGG SHOAL AND WE CAN
SEE THIS CRICKET AND WE MADE
MOVIES OF THE CRICKET AND
QUAWBTIFIED NUCLEAR THING
DEVELOPED A MATHEMATICAL MODEL
THAT WAS GOOD AT EXPLAINING THE
BEHAVIOR OF THESE NUCLEI, THE
MATHEMATICAL MODEL PREDICTED
THAT A SPECIFIC PARAMETER WHICH
WAS ACTUAL NUCLEAR DENSITY WAS A
KEY DRIVER OF ALL THE BEHAVIORS,
THE MOVEMENT AND THE MOI TO
THETIC BEHAVIORS IN THE SYSTEM.
AND THE--BUT WE DID A
COMBINATION OF REAL EXPERIMENTS
AND INSILIC O EXPERIMENTS WHERE
WE MADE EMBRYOS ARE, WE COULD
MAKE THEM IN THE COMPUTER
BECAUSE YOU COULD MAKE ANYTHING
IN A COMUTTER THAT HAD SPECIFIC
NUCLEAR DENNITYS OR SPECIFIC
SIZES AND SHAPES OR SPECIFIC
PROTURBATIONS THAT CHANGE THE
DENNITY OR PARAMETERS THAT WE
CARED ABOUT AND SEE SAID OKAY,
IF THE NUCLEI BEHAVE ACCORDING
TO THE RULE, LET'S SIMULATE THIS
AND THAT AND IN THIS THE LAB YOU
CAN DO THIS AND THAT AND CAN YOU
SEE TO WHAT EXTENT YOUR MODEL IS
A GOOD PREDICTOR OF THE REAL
WORLD.
AND SO THAT PAPER WAS JUST
ACCEPTED TODAY BY NATURE
COMMUNICATIONS, IT'S IN THE
ARCHIVES YOU CAN READ IT IF YOU
ARE INTERESTED BUT NIEWFING
FORWARD I WANT TO TAKE THE
SIMULATOR DIRECTIONS, 1 IS MORE
INSECT EGGS WE DID ANOTHER STUDY
WHERE WE SORT OF QUANTIFIED THE
MORPH O SPACE OF INSECT EGGS,
WHAT ARE SIZES AND SHAPES OF
INSECT EGGS, TURNS OUT THERE
AIAN HUGE AMOUNT OF VARIATION IN
SHAPE AND SIZE AND WE BET THAT
WE HYPOTHESIZESSED THAT THERE
WILL BE SOME FUNCTION OF THE
SAIP AND EGG ITSELF.
AND WHAT I WAS TALKING ABOUT
HERE, YOU HAVE THE BALL OF CELLS
THE BALL OF OVARY, CELL
MOVEMENT, DIRECTIONAL CELL
MOVEMENTS, FOALARRIZED CELL
MOVEMENTS, SHAPE CHANGES,
BEHAVIORS, HAVE TO HAVE IN A
SPECIFIC WAY FOR YOU TO END UP
WITH A SPECIFIC NUMBER OF
TERMINAL FILAMENTS SO WHEN I
STARTED THIS WORK YEARS AGO, I
THOUGHT LET'S MAKE MODELS AND
THEN I REALIZED WE HAVE NO
PARAMETERS TO PUT INTO THE MODEL
WE DON'T KNOW HOW MANY CELLS, WE
DON'T KNOW HOW OFTEN THEY DIVIDE
AND WHERE THEY GO, AND WE DON'T
KNOW SO NOW IT COULD BE FRUITFUL
FOR US TO DEVELOP A SIMILAR
OVARY AND SUBJECT INSILIC O
DIFFERENT ENVIRONMENTAL
MECHANICAL CELL BEHAVIORAL
CHANGES, OBSERVE WHAT THE NUMBER
OUTPUT IS, LET'S SAY YOU PICK
THAT AS AN OUTLIER THEN WE
OBSERVE WHETHER OR NOT REAL
OVOORYS SUBJECT TO THOSE SAME
SORTS OF CHANGES BEHAVING THE
SAME WAY CAN THAT WILL HELP US
KNOW SORT OF HOW FAR OFF ARE WE
IN KNOWING ALL THE DIFFERENT
PARAMETERS THAT ARE IMPORTANT TO
ULTIMATELY DETERMINE THE RIGHT
NUMBER.
>> COULD YOU COULD YOU MAKE
HYBRIDS OF THE SOME OF THE SPECS
AND LOOK AT WHAT CO SEGGREGATES
AND LOOK AT THE DOMINANT RATE?
>> HUNDRED PERCENT.
AS SUSAN KNOWS THIS IS A
QUANTITATIVE TRAIT, HIGHLY
VARIABLE AMONG THOSE THAT CAN
IRPT BREED, PRIME TERRITORY FOR
QTL ANALYSIS AND MANY RESEARCHER
VS DONE QTL ANALYSIS ON THIS
TRAIT AND THEY HAVE, UNCOVERED,
THEY--I WOULD SAY THE QTL
ANALYSIS AND THE INTERSPECIES
ACROSS THIS THAT HAVE BEEN DONE
OVER THE LAST CENTURY HAVE TOLD
US 3 MAIN THINGS, IT'S A COMPLEX
TRAIT, A LOT OF GENES IN
INVOLVED, SINGLE LOCUST AND 2
IT'S NOT SEX LINKED WHICH IS
AUTOSTUDIES OF MULTIPLE
ENDOCRINAL, AND 2 CHROMOSOMES
AND DROSOPHILA, AND 3, THE QTL
ANALYSIS THAT HAVE BEEN DONE SO
FAR HAVE UNCOVERED A NUMBER OF
LOCI, PRODETECTED I LARGER
EFFECT BUT THE TOTAL NUMBER OF
JEERNS CONTAINED IN ALL THESE IS
NUMBERING IN THE THIS HAPPENEDS
BECAUSE THE LOCI WERE A GOOD
PORTION, IT'S BEEN A GOOD NUMBER
OF YEARS SINCE ANYONE DID A
LARGE QTL, BECAUSE THE
RESOLUTIONS IT WOULD BE GREAT TO
MAP NOW.
WE TOOK A LACK AT SOME OF THOSE
OLDER QTL STUDIES AND WE PICKED
GENES WITH HIGH SCORES SO
PREDICTED TO HAVE PERHAPS A HIGH
DEGREE OF VARIATION AT THE
SEQUENCE LEVEL THAT EXPLAINS THE
VARIATION IN THE STRAIGHT AND SO
HIGH AND LOW SCORES AND WE
TESTED THEM FUNCTIONALLY,
SYSTEMATICALLY, 3 OR 400 OF
THESE WE TESTED BY KNOCKING THEM
DOWN TO ASK WHAT THE POETIC
TEBTIAL FUNCTIONAL RELEVANCE OF
THESE QTL SUGGESTED HITS MIGHT
BE.
AND THE ANSWER WAS SOMETHING
LIKE 2/3RDS OF THE LOCI AND THE
ANALYSIS UNCOVERED WHEN YOU
KNOCK THEM DOWN IN MELANO
GHASTER YOU WILL CHANGE THE
OVARIOLE NUMBER BUT NO
RELATIONSHIP WITH THE LARGE
SCORE BUT I TRIBUTE THAT TO THE
POOR RESOLUTION OF THE MAPS THAT
WERE AVAILABLE AT THE TIME AND I
THINK THE TIME NOW WOULD BE GOOD
TO REPEAT THAT.
>> THAT WOULD BE SUPER COOL.
REALLY COOL IF WE COULD
JUST--THE TECHNOLOGY'S MUCH
BETTER NOW.
>> ABSOLUTELY.
ABSOLUTELY AND ALSO RELEVANT TO
THIS AND PEOPLE HAVE DONE THIS
AS WELL, IT'S NOT TOO HARD TO
SELECT TO EXPERIMENTALLY EVOLVE
A OVARIOLE NUMBER SO CAN
YOU--LOWER OR HIGHER, BUT WHEN
YOU STOP THE SELECTIVE PRESSURE,
THOSE SNAP BACK TO THAT PEOPLE
AND SO THIS TELLS US THERE'S
HERITABILITY IN THERE, THERE'S
STANDING VARIATION AND YOU CAN
SCAN IT UP AND DOWN.
>> IT IS REVERTIBLE.
>> YOU CAN REVERT IT.
>> YOU CAN, YEAH, YEAH, YOU CAN.
QUITE EASILY.
ALL YOU HAVE TO DO IS STOP
SELECTING AND IT WILL BE SNAP
BACK.
>> SO THERE IS A CERTAIN OPTIMUM
AND YOU CAN TRANSCEND INTO DB8
BUT THEN - TAKES IT TO DEVIATE.
>> THAT'S IT.
THAT'S IT.
IT RELATED TO THE SPECIES
SPECIFIC VARIANCES, SPECIES
SPECIFIC DEGREES OF STANDING
VARIATION, GENETIC VARIATION
THAT CAN PUSH IT UP AND DOWN,
BUT GIVEN, YOU CAN'T REALLY
TRANSFORM, NOT THAT WE ARE
OTHERS HAVE SEEN YET, CAN'T
TRANSFORM A MELANO GHASTER TO 1
OF THESE DID YOU THINK BEETLE
NUMBERS OF A THOUSAND BUT IT
WOULD BE GREAT, INTERESTING TO
TRY.
YEAH, CHRIS IS TELLING ME WE
SHOULD COME TO AN END AND GIVE
YOU BREAK BEFORE YOU MEET WITH
THE STUDENTS.
THANK YOU AGAIN SO MUCH FOR THE
TALK THAT WAS AMAZING AND I
GUESS EVERYONE ENJOYED IT AS
MUCH AS I DID, SO THANK YOU VERY
MUCH FROM ALL OF US.
AND ALSO AVAILABLE ON VIDEOCAST
FOR ALL THE OPPORTUNITY
TO WATCH IT LIVE.
THANK YOU VERY MUCH, WONDERFUL
MEETING YOU.
>> THANK YOU SO MUCH EVERYBODY.
BYE.