>> GOOD AFTERNOON, EVERYONE.
IT'S A GREAT PLEASURE TO WELCOME
YOU TO THE FIRST WEDNESDAY
AFTERNOON LECTURE OF THIS
PARTICULAR ACADEMIC SEASON.
AND IT'S GREAT TO SEE SO MANY
PEOPLE HERE IN MASUR, AND I KNOW
THERE ARE MANY OTHERS WATCHING
BY VIDEO, AND WE WELCOME YOU AS
WELL.
WE DO THIS ON MOST WEDNESDAYS,
WE BRING IN AN AMAZING SET OF
LECTURERS THAT COME HERE TO TELL
US THEIR LATEST RESULTS.
NEXT WEEK, BY THE WAY, WILL BE
CARL JEUNE, ONE OF THE LEADERS
OF CANCER IMMUNOTHERAPY FROM THE
UNIVERSITY OF PANCREATIC
ADENOCARCINOMA, SO I'M SURE YOU
WANT TO COME AND HEAR WIT ABOUT
THAT
AS WELL.
PERSONAL PLEASURE FOR ME TO BE
ABLE TO INTRODUCE TODAY'S
SPEAKER, DAVID REICH.
HIS WORK IN THE AREA OF
UNDERSTANDING HUMAN ORIGINS IS
AT THE VERY LEADING EDGE ON
QUESTIONS THAT ALL OF US HAVE
ASKED FOR SENT KREN CENTURY,
MILLENNIUMS,
ABOUT WHERE WE CAME FROM AND HOW
WE'RE ALL RELATED, AND USING THE
TOOLS OF MODERN GENOMICS AND
SOME PRETTY GOOD SLEUTHING AND
EPIDEMIOLOGY AND FIGURING OUT
HOW TO DERIVE DNA FROM ANCIENT
BONES.
DAVID HAS BEEN SUCCESSIVELY,
OVER THE SPACE OF SEVERAL YEARS,
ADDING MORE AND MORE DETAILS TO
THAT MAP OF INFORMATION ABOUT
OUR ORIGINS AND HOW ALL OF US,
ORIGINALLY AFRICANS, HAVE ENDED
UP IN OTHER PARTS OF THE WORLD,
AND HOW THE STUDY OF DNA CAN
TEACH US ABOUT THOSE HISTORICAL
EVENTS IN WAYS THAT HAVE REALLY
REMARKABLE DETAIL ATTACHED TO
THEM.
IT'S ALSO A PARTICULAR PLEASURE
TO HAVE DAVID HERE AS OUR
SPEAKER BECAUSE IT'S KIND OF A
FAMILY THING, MANY OF YOU KNOW
DAVID'S BROTHER, DANNY REICH,
WHO'S SITTING THERE IN THE BLUE
SHIRT, ONE OF OUR DISTINGUISHED
PRINCIPAL INVESTIGATORS IN THE
NEUROIMAGING ARENA AND SOMEBODY
THAT WE HAVE ASKED MANY TIMES TO
TALK ABOUT HIS RESEARCH TO
DISTINGUISHED VISITORS AT
VARIOUS MOMENTS, INCLUDING
HIGH-RANKING OFFICIALS OF THE
UNITED STATES GOVERNMENT BUT WHO
DOES WONDERFUL RESEARCH IN THE
AREA OF MULTIPLE SCLEROSIS AND
OTHER THINGS.
AND I'M ALSO VERY HAPPY TO POINT
OUT THAT DANNY AND DAVID'S
PARENTS ARE HERE ALSO, SITTING
ON EITHER SIDE OF HIM, AND HIS
DAD WAS ONCE HERE AS NIH AS AN
INVESTIGATOR IN NIMH.
SO THIS IS REALLY A WONDERFUL
FAMILY OCCASION THAT WE HAVE
HERE.
WELL, TO SAY VERY BRIEFLY A
COUPLE WORDS ABOUT DAVID SO I
DON'T TAKE ANY MORE OF HIS TIME,
HE IS CURRENTLY PROFESSOR OF
GENETICS AT HARVARD, ASSOCIATE
MEMBER OF THE BROAD INSTITUTE,
HE'S HAN INVESTIGATOR IN THE
HOWARD HUGHES MEDICAL INSTITUTE,
AND HIS UNDERGRADUATE WORK IN
HARVARD AS PHYSICS, ALWAYS A
GOOD START FOR SOMEBODY WHO'S
GOING TO BE PRETTY DARN
QUANTITATIVE AND PRETTY
MATHEMATICAL AS WELL.
AFTER THAT, STATISTICAL GENETICS
AT THE UNIVERSITY OF OXFORD,
WHERE HE WAS WITH DAVID
GOLDSTEIN, AND THEN ON TO
HARVARD MEDICAL SCHOOL AND MIT,
BUT ENDING UP AT THE WHITEHEAD
FOR A POSTDOC IN MEDICAL
GENETICS THEN TO HARVARD AND THE
APPOINTMENTS I JUST MENTIONED AT
THE BRODE AND HOWARD HUGHES.
HIS WORK HAS BEEN RECOGNIZED BY
A VARIETY OF SPECIAL AWARDS, THE
NEW CLEVELAND PRIZE FROM AAAS
FOR THE BEST PAPER IN SCIENCE OF
THE YEAR IN 2010, THE
OUTSTANDING ACHIEVEMENT AWARD
NAMED AS ONE OF NATURE'S 10
PEOPLE WHO MATTER THIS YEAR BY
"NATURE" MAGAZINE LAST YEAR.
HAPPY TO CLAIM HIM AS A P.I. AND
CO-P.I. ON SEVERAL GRANTS FROM
NIH, AND AS YOU WILL HEAR, HAPPY
TO SAY THE WAY IN WHICH HIS
RESEARCH IS EVOLVING IN
FASCINATING WAYS, INCLUDING, BY
THE WAY, THAT HIS PAPER IN
"NATURE" CAME OFF EMBARGO AT
1:00 TODAY, SO IT'S A VERY GOOD
BIT OF TIMING TO HAVE HIM HERE
TO TALK ABOUT THE LATEST
FINDINGS.
SO PLEASE JOIN ME IN WELCOMING
DR. DAVID REICH.
[APPLAUSE]
>> DO PEOPLE HEAR ME?
THANK YOU.
IT'S REALLY A GREAT HONOR TO
COME SPEAK HERE AND TO BE
INVITED TO GIVE THIS LECTURE TO
THE NIH.
I'M GOING TO TELL YOU ABOUT A
NEW SCIENTIFIC INSTRUMENT THAT'S
BEEN DEVELOPED IN THE LAST
REALLY FIVE OR SIX YEARS AND
THAT'S REALLY MADE IT POSSIBLE
TO STUDY THINGS THAT WERE NOT
POSSIBLE TO STUDY BEFORE, AND
I'M GOING TO TELL YOU ABOUT WORK
THAT I'VE BEEN INVOLVED IN, IN
TRYING TO USE THIS SCIENTIFIC
INSTRUMENT TO LEARN NEW THINGS.
SO I HOPE THAT AT THE END OF
THIS LECTURE, YOU WILL
APPRECIATE THE POWER OF THIS NEW
TOOL AND ITS POTENTIAL TO LEARN
A LOT OF NEW THINGS.
SO I'M FIRST GOING TO TELL YOU
ABOUT THIS NEW SCIENTIFIC
INSTRUMENT, ANCIENT DNA, SO THIS
IS AN INSTRUMENT THAT WAS NOT
INVENTED ON THIS CONTINENT, IT
WAS REALLY DEVELOPED ALMOST
ENTIRELY IN EUROPE BY EUROPEAN
LABORATORIES, ESPECIALLY PAVOS
LABORATORY IN GERMANY, BUT NOW
HAS BECOME A TECHNOLOGY THAT
OTHER GROUPS CAN USE AS WELL
BECAUSE OF THE WORK DONE THERE
AND ELSEWHERE.
SO IT STARTS WITH A BONE FROM IN
THIS CASE A HUMAN.
I WORK ON HUMAN BONES MOSTLY,
BUT OTHER LABORATORIES WORK ON
OTHER TYPES OF SKELETAL REMAINS.
WE TAKE THE BONE INTO A CLEAN
ROOM, WHICH IS A CONTROLLED
ENVIRONMENT WHERE THERE'S
POSITIVE PRESSURE SO THAT THE
DNA FROM THE OUTSIDE THE CLEAN
ROOM DOESN'T GET INSIDE THE
CLEAN ROOM.
THE DANGER IS CONTAMINATION OF
THESE SAMPLES WHICH HAVE SO
LITTLE DNA IN THE FIRST PLACE.
THERE IS UV LIGHT WHEN PEOPLE
AREN'T THERE TO CROSS LINK THE
DNA SO THAT YOU DON'T SEQUENCE
DNA THAT'S FROM THE RESEARCHERS
IN THE ROOM.
PEOPLE WEAR BODY SUITS AND
THERE'S A LOT OF CLEANING WITH
BLEACH AND USE OF HOODS IN ORDER
TO CLEAN SAMPLES.
ONE DRILLS BENEATH THE SURFACE
OF THE BONE WITH A LITTLE BORE
HOLE TO REMOVE -- TO TRY TO GET
BEYOND WHERE IT MIGHT HAVE BEEN
CONTAMINATED BY ARCHAEOLOGISTS
OR WHOA PEOPLE WHO HAVE HANDLED
THE
BONE, IT CONTAINS A BIT OF
POWDER.
THAT POWDER IS REMINERALIZED AND
PROTEINS ARE REMOVED THROUGH A
SERIES OF CHEMICAL STEPS AND
THEN TURNED INTO SEQUENCABLE
FORM WITH ONE OF THE MODERN
SEQUENCERS TO PRODUCE A LOT OF
DATA.
SO THAT'S THE BASIC SORT OF
STEPSET OF STEPSUSED TO GET DNA
OUT OF SAM
PLES,
AND THERE'S A WHOLE BUNCH OF
OPTIMIZATION THAT HAS BEEN
IMPLEMENTED IN ORDER TO MAKE
THIS MORE EFFICIENT AND INCREASE
THE AMOUNT OF DNA THAT ONE CAN
GET OUT OF A SAMPLE BY LITERALLY
10,000 TIMES OVER THE LAST SIX
YEARS.
SO I'M JUST GOING TO START WITH
A PICTURE OF MOORE'S LAW.
SO MOORE'S LAW IS ABOUT COMPUTER
WORLDS AND IT'S WHERE THE NUMBER
OF ELEMENTS ON INTEGRATED
CIRCUITS DOUBLES EVERY ONE TO
TWO YEARS, AND THAT'S BEEN GOING
ON FOR THE LAST CENTURY, AND
IT'S DRIVEN THE COMPUTER
EVOLUTION.
SO THERE IS A MOORE'S LAW OF
ANCIENT DNA BUT THE RISE HAS
BEEN MUCH FASTER AND MORE
RECENT, SO IN 2010 -- AND I'M
TELLING YOU HERE ABOUT WHOLE
GENOME DATA, NOT JUST
MITOCHONDRIAL DNA SEQUENCES BUT
JUST WHOLE GENOME DATA WHERE
THERE'S ENOUGH TO REALLY LEARN
ABOUT POPULATION VARIATION.
SO IF YOU USE AS A CUTOFF AN
AMOUNT WHERE YOU CAN BEGIN TO
LEARN ABOUT POPULATION
RELATIONSHIPS, THERE WERE FOUR
SEQUENCES PUBLISHED IN 2010,
THERE WERE A BURST OF 20 OR 30
SEQUENCES PUBLISHED IN 2014, AND
THEN IT WENT INTO HYPERDRIVE IN
2015 WITH SEVERAL HUNDRED
SEQUENCES AND IT'S INCREASING
AND INCREASING, NOW WE HAVE MORE
THAN A THOUSAND SEQUENCES IN OUR
LABORATORY AND I'M SURE THAT'S
TRUE ALSO OF OTHER LABORATORIES,
AND THERE'S SO MUCH DATA BEING
PRODUCED RIGHT NOW THAT THERE'S
MUCH MORE DATA THAT'S
UNPUBLISHED --
THAT'THANPUBLISHED JUST BEC
AUSE THERE'S
NOT ENOUGH TIME TO PUBLISH IT.
WHAT WE'VE DONE IN OUR
LABORATORY, I GUESS IT'S A VERY
AMERICAN THING DO, IS TO MAKE
THESE BEAUTIFUL TECHNIQUES
DEVELOPED IN EUROPE, BEAUTIFUL
PIECE WORK TECHNIQUES, TO MAKE
THEM INDUSTRIAL.
AND SO WE TRY TO TAKE THE OLD
APPROACH, WHICH IS STILL A
WONDERFUL APPROACH, SEARCHING
FOR A GOLDEN SAMPLE, SCREENING
AND SCREENING AND SCREENING
THESE SKELETAL REMAINS FOR SOME
SAMPLE THAT WILL HAVE ENOUGH DNA
THAT IT CAN BE SEQUENCED AND
THEN WORKING VERY HARD ON IT, TO
PROCESS WHERE WE SCREEN MANY,
MANY SAMPLES AND USE -- AND TAKE
ADVANTAGE OF EFFICIENCIES AND
TECHNIQUES THAT MAKES IT
POSSIBLE TO CONVERT A HIGHER
FRACFRACTION OF SAMPLES TO
PROVIDE
THE INFORMATION WE NEED.
SO OUR GOAL WAS TO IMPLEMENT A
SCREENING PROCESS THAT WOULD
TURN A LARGE FRACTION OF THE
SAMPLES WE ANALYZE INTO WORKING
DATA, AND TO HAVE A REASONABLE
COST PER SAMPLE TO PRODUCE
GENOME-WIDE DATA, IN OUR CASE,
LESS THAN $500 A SAMPLE.
ONE OF THE REASONS ANCIENT DNA
IS SO EXPENSIVE AND CONTINUES TO
BE SO EXPENSIVE IN MOST
IMPLEMENTATIONS IS THAT BECAUSE
SO LITTLE ANCIENT DNA IS HUMAN,
BONES ARE MOSTLY -- THE DNA YOU
GET OUT OF BONES IS MOSTLY
MICROBIAL, IT'S FROM THE
BACTERIA AND FUNGI THAT ATE YOU
WHEN YOU DIED, SO VERY LITTLE OF
THE DNA THAT YOU SEQUENCE IS
FROM THE INDIVIDUAL YOU WANT TO
SEQUENCE.
EVEN IF IT'S AN UNCONTAMINATED
SAMPLE.
BEYOND THAT, OF COURSE, MOST OF
THE DNA THAT YOU SEQUENCE EVEN
FROM A HUMAN IS NOT FROM THE
SECTIONS OF THE GENOME YOU
PROBABLY ARE GOING TO WANT TO
ANALYZE, PERHAPS FOR STUDYING
POPULATION RELATIONSHIPS.
SO THE SOLUTION THAT WE TOOK WAS
A SOLUTION WHICH IS AN
ADAPTATION OF A METHOD DEVELOPED
BY KIAOMEI FU AND MATHIAS MEYER,
AND WHAT WE DO IS WE TAKE THE
DNA SAMPLE, MADE INTO
SEQUENCABLE FORM FROM THE DAB
LIBRARY AND WE TAKE A TECHNIQUE,
EXOME SEQUENCING, WE WASH IT
OVER A SERIES OF 50 DNA LETTER
LONG SEQUENCES THAT TARGET THE
AREA OF THE GENOME WE'RE
INTERESTED IN, AND WHAT'S LEFT
IS NOT ONLY FROM HUMAN BUT THE
REAMES WE'RE INTERESTED IN, SO
MOST OF WHAT WE'RE LEFT WITH IS
THE AREAS WE'RE INTERESTED IN
AND THEN IT'S NOT A LOT OF
SEQUENCING TO OBTAIN DATA FROM
THESE APPROXIMATELY 1 MILLION
POSITIONS IN THE GENOME.
SO WE'RE CURRENTLY SCREENING AND
PRODUCING -- SCREENING MORE THAN
A THOUSAND SAMPLES PER YEAR IN
OUR LABORATORY, WHICH IS A HUGE
CHANGED COMPARED TO THE
SITUATION IN THE PAST, WE'RE NOT
THE ONLY LABORATORY THAT'S ABLE
TO SCREEN SUBSTANTIAL NUMBERS OF
SAMPLES BUT IT'S REALLY
TRANSFORMATIVE IN TERMS OF WHAT
IT ALLOWS US TO DO.
SO THIS ARROWS U ALLOWS US TO
REDUCE COST
AND IMPROVE QUALITY.
THIS WAS A WONDERFUL EXAMPLE
PUBLISHED LAST YEAR IN DENMARK
WHICH TOOK ABOUT 100 SAMPLE,
SEQUENCED THEM, BRUTE FORCE, BY
RUNNING THE SAMPLES THROUGH THE
SEQUENCER.
THIS IS THE NUMBER OF SEQUENCES
IN THE HUNDREDS OF THOUSANDS AND
APPROXIMATELY THE SAME COST IN
DOLLARS, AND THIS WAS A MILLION
DOLLAR EXPERIMENT WHERE ON
AVERAGE, ABOUT .20% OF POSITIONS
IN THE GENOME WERE COVERED, BUT
WHEN WE APPLY THIS APPROACH, WE
HAVE MANY FEWER SEQUENCES
REQUIRED AND THAT WE THINK ARE
MOST INTERESTING TO ANALYZE.
SO IT ALLOWS A GREAT AMOUNT OF
EFFICIENCY AND MAKES IT ECONOMIC
TALL TO DO THIS KIND OF WORK.
I'M REQUESTING TO TELL YOU IN
THE SECOND PART OF MY TALK A
SPECIFIC EXAMPLE ABOUT HOW
ANCIENT DNA HAS PROVIDED NEW
INSIGHTS ABOUT THE PAST, AND I'M
GOING TO TALK ABOUT EUROPE AND
ABOUT WESTERN EURASIA MORE
BROADLY, NOT BECAUSE THESE ARE
PARTICULARLY IMPORTANT PLACES OF
THE WORLD BUT IT'S BECAUSE WE
KNOW THE MOST.
SO THIS TECHNOLOGY OF ANCIENT
DNA WAS DEVELOPED IN EUROPE, AND
BECAUSE OF THAT WE HAVE MUCH
MORE DATA, ABOUT 90% OF THE
GENOME WIDE DATA IN THE
LITERATURE IS FROM EUROPE OR
WESTERN EUR ASIA, JUST AS
INTERESTING THINGS CAN BE DONE
IN THE AMERICAS, SOUTH ASIA,
AFRICA, BUT I'M GOING TO TELL
BUT EUROPE TO ILLUSTRATE THE
POWER OF THESE APPROACHES.
SO THE BACKGROUND FOR THIS IS TO
START WITH PRESENT DAY, AND I
WANT TO FRAME THIS IN THE
FOLLOWING WAY.
SO WEST EURASIANS, WHICH MEANS A
REGION THAT EXTENDS FROM EUROPE,
ON THE ATLANTIC COAST OF EUROPE,
ALL THE WAY TO RNA AND CENTRAL
ASIA, IN THE MIDDLE OF ASIA, ARE
GENETICALLY VERY SIMILAR, SO IF
YOU MEASURE THE SQUARE OF THE
FREQUENCY DIFFERENCE, THAT
GENETIC VARIANCE, IT'S NOT VERY
DIFFERENT.
THIS IS ACTUALLY WHAT GAVE RISE
IN THE 18TH CORRECT RETO
SCIENTIFIC CLASSIFICATIONS OF
PEOPLE INTO DIFFERENT GROUPS,
THE SORT OF OBSERVATION TO
PEOPLE THAT GENETICALLY ARE
SIMILAR ACROSS THIS REGION.
IF YOU LOOK AT SOME GENETIC
VARIANTS, YOU CAN SEE THIS.
SO THIS IS A PIE CHART,
FREQUENCY OF VARIANTS THAT SOME
PEOPLE OF ONE TYPE AND -- THESE
ARE VERY UNUSUAL VARIANTS
DIFFERENT IN FREQUENCY, SO YOU
SEE EURASIA CLUSTERING, AND EAST
ASIANS FROM KOREA TO INDONESIA,
AGAIN, THERE'S GENETIC
SIMILARITY THEN A BIG SHARP
DIVISION MOVING INTO WESTERN
EURASIA AND IN MUCH OF AFRICA,
BUT NOT ALL OF AFRICA, AGAIN, A
LOT OF SIMILARITY.
AND A QUESTION IS, HOW DID THIS
HOPE JE NATE ACROSS THESE
REGIONS ARISE?
I THINK PEOPLE CENTURIES AGO,
WHEN PEOPLE FIRST BEGAN TRYING
TO MAKE THESE CAT IMRI, THOUGHT
CATEGORIES
 THOUGHT
THESE ARE AGE OLD THINGS, SINCE
POPULATIONS SEPARATED FROM EACH
OTHER OR MAYBE LONGER, IT EVEN
ALWAYS EXISTED.
IN FACT THE ANSWER IS, THESE ARE
ONLY 5,000 YEARS OLD, THESE
CLUSTERS THAT WE SEE TODAY, AND
FROM ANCIENT DNA, WE KNOW THIS,
AND I'M GOING TO TELL YOU HOW WE
KNOW THIS IN THE CASE OF EUROPE.
I'M GOING TO FIRST TELL YOU
ABOUT EUROPE SPECIFICALLY AND
I'M GOING TO TELL YOU HOW
EUROPEANS TODAY ARE THE RESULT
OF MASSIVE MIXTURE OF THREE
HIGHLY DIFFERENT POPULATIONS
THAT ARE AS DIFFERENT FROM EACH
OTHER AS EUROPEAN AND EAST ASIA
BUT IT ALL HAPPENED IN THE LAST
9,000 YEARS.
SO I'M JUST GOING TO FIRST
INTRODUCE A FEW PIECES OF
EVIDENCE FROM OUTSIDE GENETICS.
THE EVIDENCE OF ARCHAEOLOGY AND
THE EVIDENCE OF LANGUAGE.
SO WHAT YOU NEED TO KNOW ABOUT
THE ARCHAEOLOGY OF EUROPE,
THERE'S MANY THINGS, BUT ONE
VERY IMPORTANT THING IS THE
ARRIVAL OF FARMING IN EUROPE.
SO FARMING WAS NOT INVENTED IN
EUROPE, IT WAS INVENTED IN THE
NEAR EAST BEGINNING BETWEEN
12,000 AND 11,000 YEARS AGO,
PROBABLY IN PRESENT-DAY TURKEY
OR SYRIA, AND -- OR RAC, AND THE
SPREAD FROM THERE, REACHING
PRESENT DAY GREECE ABOUT 3,000
YEARS LATER AND IT REACHED
BRITAIN AND SCANDINAVIA BY ABOUT
6,000 YEARS AGO, IT SPREAD
ACROSS EUROPE DRAMATICALLY,
POPULATIONS INCREASED, THE TYPES
OF FOOD PEOPLE ATE COMPLETELY
CHANGED, THIS WAS A DRAMATIC
CHANGE.
THE QUESTION HAS ALWAYS BEEN
WHETHER THIS MASSIVE
TRANSFORMATION ECONOMICALLY WAS
ACCOMPANIED BY MOVEMENTS OF
PEOPLE, THERE WAS A LOT OF
SKEPTICISM THAT THERE MIGHT BE
SUCH BUT IT WAS ALWAYS A
QUESTION ABOUT WHETHER IT WAS
MOVEMENTS OF PEOPLE OR JUST
ADAPTION OF IDEAS.
WE ALL USE CELL PHONES RIGHT
NOW, BUT WE DIDN'T -- WE'RE NOT
ALL ETHNICALLY GENETICALLY THE
SAME, AND WE ADAPT IDEAS FROM
OTHER PEOPLE, SO MAYBE FARMING
WAS ADOPTED BY -- FROM PEOPLE'S
NAPE NAIBS OPEOPLE'SNEIGHBORS OR
DID IT SP
READ
THROUGH PEOPLE.
THE OTHER OPTION IS LANGUAGES,
SO PEOPLE IN EURM WITH EXCEPTION
OF HUNGARIAN, FINNISH --
ENDOEUROPEAN LANGUAGES LEFT A
GREAT GAP IN BETWEEN IN THE NEAR
EAST AND WE KNOW IT'S BEEN A GAP
WHERE IT'S -- WRITING WAS
INVENTED IN THE NEAR EAST AND WE
KNOW FOR THE LAST -- THERE
HASN'T BEEN THESE LANGUAGES IN
THIS REGION.
SO WHAT IF -- HOW DOES THIS
CORRESPOND TO MOVEMENTS OF
PEOPLE?
SO IN 2009 AND THEN WITH
GENOME-WIDE DATA IN 2012, IT
BECAME ABSOLUTELY CLEAR FROM
GENOME-WIDE DATA THAT THE
ARRIVAL OF FARMERS IN EUROPE WAS
ACCOMPANIED BY HUGE MOVEMENTS OF
PEOPLE.
AND THE WAY THIS WAS KNOWN IS
THAT PEOPLE SUCCESSFULLY GOT
MITOCHONDRIAL DNA, THE DNA IN
THE ENERGY FAK TREES OF YOUR
SELL, ABOUT 15,000 DNA LETTERS
LONG, BUT IT WAS THE PART OF THE
DNA THAT FIRST PEOPLE BEGAN TO
STUDY WITH ANCIENT DNA BECAUSE
THERE'S ABOUT A THOUSAND TIMES
MORE COPY PER CELL AND THE
CHALLENGE IN DNA IS TO GET
ANYTHING AT ALL FROM THESE BONES
SO PEOPLE STARTED WITH WHAT
THERE WAS THE MOST OF.
SO WHEN PEOPLE STUDIED DNA
SEQUENCES FROM HUNTER GATHERERS
FROM EUROPE, FROM 8,000 YEARS OR
9,000 OR 10,000 YEARS AGO, WHAT
THEY FOUND WAS ALL OF THE
MITOCHONDRIAL SEQUENCES, A GREAT
MAJORITY WERE OF TWO TYPES, WHAT
THEY CALLED U4 AND U5, BUT THE
FIRST FARMER HS ALMOST NO U4U5,
CLEARLY EVIDENT OF PEOPLE COMING
IN FROM ELSEWHERE.
GENOME-WIDE DATA FROM PEOPLE
FROM 5,000-YEAR-OLD -- YEARS AGO
IN SWEDEN WAS SUBSTANTIALLY
AFTER THE FIRST ARRIVAL OF
FARMING, LED BY PONTIFF SCOGLAND
AND COLLEAGUES, THEN SHOWED THAT
5,000 YEARS AGO, THE FIRST
FARMERS OF NORTHERN EUROPE AND
SCANDINAVIA WERE GENETICALLY
VERY DIFFERENT FROM THE HUNTER
GATHERERS LIVING SIDE BY SIDE,
BUT ABOUT AS DIFFERENT FROM EACH
OTHER AS EUROPEANS AND EAST
ASIANS AND THAT, IN FACT, WERE
GENETICALLY VERY SIMILAR NOT TO
PRESENT DAY PEOPLE FROM SWEDEN
BUT PRESENT DAY PEOPLE FROM
SARDINIA AND THEY HAD A MODEL
WHERE PEOPLE ARE OF TWO
ANCESTRAL POPULATIONS, THE
FARMERS WHO HAVE LEFT THE MOST
ANCESTRY IN PEOPLE TODAY IN
SARDINIA, AND THAT PEOPLE TODAY
ARE A MIXTURE OF THESE TWO
SOURCES, SO THAT WAS THE MODEL.
BUT IN 2012, WE HAD IN OUR
LABORATORY ANOTHER OBSERVATION
WHICH WAS HARD TO RECONCILE WITH
THIS MODEL AND IT WAS THIS:  SO
WHAT WE FOUND IS WE DEVELOPED A
STATISTIC CAL TEST, THE
THREE-POPULATION TEST.
WE TAKE GENETIC VARIATION DATA,
SO WHAT WE'RE LOOKING AT IS
HUNDREDS OF THOUSANDS OF
POSITIONS IN THE GENOME, WHERE
SOME PEOPLE HAVE ONE TYPE AND
SOME HAVE ANOTHER TYPE AND WE
CAN -- [INAUDIBLE] SO WHAT WE
DID IS WE TAKE A SET OF THREE
POPULATIONS, A TEST POPULATION
THAT WE'RE TESTING TO SEE
WHETHER IT'S MIXED AND THEN TWO,
POSSIBLE SOURCE POPULATIONS.
IF THE TEST POPULATION IS MIXED
OF LINEAGES THAT ARE RELATED
SOMETIME IN THE PAST TO THE
SOURCE POPULATIONS, THE
PREDICTION IS, IS THAT THE
FREQUENCIES OF THESE GENETIC
VARIANTS IN THE TEST POPULATION
WILL TEND TO BE INTERMEDIATE
BETWEEN THE TWO SOURCE
POPULATIONS BECAUSE IT'S MIXED.
SO WE CAN TEST THIS OR THE
FREQUENCIES TEND TO BE
INTERMEDIATE AT ANY ONE
POSITION, WE CAN'T MEASURE THAT
WITH ANY RELIABILITY, BUT IF WE
AVERAGE OVER HUNDREDS OF
THOUSANDS OF PHYSICIANS WE CAN
OBTAIN A VERY PRECISE
DETERMINATION OF WHETHER THE
FREQUENCIES ARE ON AVERAGE
INTERMEDIATE IN THE TEST
POPULATION RELATIVE TO THE
SOURCE POPULATION.
SO WE HAVE THIS TEST IN HAND,
AND WE RAN THIS TEST ON ABOUT 50
WORLDWIDE POPULATIONS, PRESENT
DAY ONES, AND WE LOOKED FOR
WHETHER EACH POPULATION HAD
MIXTURE FROM ANY PAIR OF THE
HOAR TWO.
SOTHER TWO.
SO WHAT WE FOUND IS THAT IN
NORTHERN EUROPEANS, PRESENT DAY
FRENCH PEOPLE, THERE'S A HUGE
SIGNAL OF MIXTURE.
ONE OF THEM, THE SOURCE
POPULATIONS IS SARDINIAN,
CONSISTENT WITH THE IDEA THESE
ARE FIRST FARMERS, AND THE OTHER
WAS NOT NORTHERN EUROPEANS OR --
BUT IT WAS NATIVE AMERICANS, SO
THIS IS A REALLY WEIRD
OBSERVATION, AND IT DEFINITELY
WAS NATIVE AMERICANS, IT WAS NOT
SIBERIAN, IT WAS NOT SOUTH
ASIANS, IT WAS NOT EAST ASIANS,
THE NATIVE AMERICANS GAVE A MUCH
STRONGER SIGNAL.
AND WHAT WE PROPOSED WHAT WAS
ACTUALLY GOING ON THERE WAS IN
NORTHERN EURASIA AT SOME POINT
IN THE PAST MORE THAN 15,000
YEARS AGO WHAT WE CALL A GHOST
POPULATION, A MAJOR POPULATION
THAT LIVED IN NORTHERN EURASIA
IN THE PAST, MORE THAN 15,000
YEARS AGO, AND CONTRIBUTED SOME
OF THE ANCESTRY OF NATIVE
AMERICANS LIVING TODAY AND THAT
SOMETIME LATER ALSO CONTRIBUTED
ANCESTRY TO EUROPEANS.
SO THIS POPULATION DOESN'T EXIST
IN A MIXED FORM ANYMORE, IT'S
BEEN LARGELY DISPLACED SINCE,
EXPLAINING WHY PEOPLE IN SYBERIA
TODAY ARE NOT AS GOOD A SOURCE
FOR EUROPEAN MIXTURE, AS ARE
NATIVE AMERICANS, BUT THE
POPULATION EXISTED IN THE PAST.
SO WE CALL THEM AIN SHANT NORTH
YOU'RE ASIANS AND WE THINK
THEY'VE CONTRIBUTED ANCESTRY TO
THE AMERICAS AND ALSO NORTHERN
EUROPEANS.
SO THAT WAS THE PROPOSAL OF A
GHOST POPULATION STATISTICALLY
RECONSTRUCTED BASED ON PRESENT
TADAY POPULATIONS, NO DATA FROM
IT.
SO WHAT WAS VERY EXCITING TO US
WAS AT THE END OF THE NEXT YEAR,
THIS GHOST WAS FOUND, ANCIENT
DNA GROUP WORKING IN DENMARK,
AND THEY SEQUENCED DNA FROM THE
24,000-YEAR-OLD INDIVIDUAL, A
BOY FROM THE LATE -- REGION OF
EAST CENTRAL SYBERIA.
THIS INDIVIDUAL WAS MORE CLOSE
LOW RELATED TO EUROPEANS EVEN
THAN NATIVE AMERICANS ARE, AND
WAS CLEARLY THE CORRECT SOURCE
POPULATION FOR THE ANCESTRY BOTH
IN THE AMERICAS AND IN EUROPE,
TODAY THE DARK BLUE IN THE HEAT
MAP SHOWS THERE'S NOT MUCH
ANCESTRY LIKE THAT ANYMORE,
REFLECTING THE FACT THAT MOST OF
THE INDIGENOUS PEOPLE OF SYBERIA
TODAY ARE THE RESULTS OF
MIGRATIONS THAT HAVE BROUGHT
PEOPLE INTO THIS REGION FROM
ELSEWHERE MORE CLOSELY RELATED
TO EAST ASIANS THAN PEOPLE WERE
IN -- AT THAT TIME.
SO THIS IS VERY EXCITING TO US
THAT WE COULD SEE THE ECHOS OF A
GHOST POPULATION RICH IN GENETIC
FROM PRESENT DAY PEOPLE AND THAT
IT COULD PREDICT ANCIENT DNA,
BUT ONCE THAT WAS IN HAND,
EVERYTHING BECAME MUCH MORE
CLEAR BECAUSE IT'S MUCH EASIER
TO LOOK AT IT DIRECTLY THAN TO
STUDY IT INCORRECTLY.
SO WHAT WE DID, IN WORK LED BY
JOSEPH LAZARIDIS WITH JO KRAUSE,
TO
COMPARE TO THIS ANCIENT GENOME
GENERATED BY THE DANISH GROUP
AND TO TRY TO BUILD A POPULATION
OF RELATIONSHIP.
SO I'M GOING TO NOW DIGRESS FOR
2 MINUTES TO TRY TO TELL YOU
WITH HOW WE LOOK AT OUR GENETIC
DATA.
SO THIS IS DATA FROM
777 PRESENT-DAY INDIVIDUALS FROM
WEST EURASIA, SO WEST EURASIA
REFERS TO THIS GROUP OF PEOPLE
WHO ARE GENETICALLY PRETTY
SIMILAR TO EACH OTHER, INCLUDING
YOU'RE PEEPS AND CENTRAL ASIANS
AND NEAR EASTERNERS, AND
PEOPLE -- THE DOTS ARE COLORED
BY WHICH POPULATION INDIVIDUALS
ARE FROM, BY SELF IDENTIFIED
ANCESTRY, ALTHOUGH THE SELF
IDENTIFIED ANCESTRY IS NOT USED
IN THE MATHEMATICAL TECHNIQUE
USED TO DISPLAY THESE POINTS.
SO THE NATURE OF THE DATA WE
HAVE IS SINGLE NUCLEOTIDE
POLYMORPHISM GENOTYPE ARRAY
DATA.
WHAT THIS MEANS IS THAT WE OR
OTHERS HAVE LOOKED AT A -- I'VE
TAKEN A GENOTYPING SHIP WHICH
INTERROGATES EACH INDIVIDUAL AT
ABOUT 600,000 POSITIONS IN THE
GENOME.
AND SCORES THAT INDIVIDUAL FOR
WHAT THEY HAVE, SO AT EACH
POSITION THEY WILL HAVE ZERO,
ONE OR TWO COPIES OF THE
MUTATION THE CHIMPANZEE DOESN'T
HAVE, FOR EXAMPLE.
AND THERE ARE ABOUT 600,000 ROWS
CORRESPONDING TO EACH OF THESE
POSITIONS AND 777 COLUMNS
CORRESPONDING TO EACH OF THE
INDIVIDUALS.
WE THEN MULTIPLY THE MATRIX BY
ITSELF AND SEE HOW CLOSE EACH
INDIVIDUAL IS TO EACH OTHER
INDIVIDUAL AND THAT'S A MEASURE
OF GENETIC SIMILARITY OF ALL OF
THESE INDIVIDUALS AND THEN WE
RUN PRINCIPAL COMPONENT ANALYSIS
ON THAT AND THAT SEPARATES THE
SAMPLES ACCORDING TO THE MOST
EFFICIENT WAY OF SEPARATING
THEM.
SO FOR EXAMPLE, THE FIRST
PRINCIPLE COMPONENT MIGHT BE .3
TIMES THE VALUE AT POSITION
1 MINUS .2 TIMES THE VALUE AT
POSITION 2, AND PRINCIPLE
COMPONENT 2 MIGHT BE SOME OTHER
COMBINATION.
THE MATHEMATICS WILL EFFICIENTLY
SEPARATE SAMPLES IN THIS WAY.
SO WHEN WE RUN THIS ON PRET DAY
WEST YOU'RE ASIANS, WE SEE A
REALLY DRAMATIC PATTERN OF TWO
PARALLEL GRADIENT.
ALL EUROPEANS ALMOST WITHOUT
EXCEPTION FALL IN THIS GRADIENT
WITH SAR DINNIANS AT THE BOTTOM
END AND NORTHEAST EUROPEANS AT
THE OTHER END AND DIFFERENT
POINTS INTERMEDIATE, AND ALL
NEAR EASTERNERS, ALMOST WITHOUT
EXCEPTION, FOLLOW THIS GRADIENT
WITH ARMANIANS HERE AND PEOPLE
FROM THE SOUTHEAST OVER DOWN
HERE.
SO THERE ARE VERY FEW
INTERMEDIATE POPULATIONS, THE
POPULATIONS THAT ARE
INTERMEDIATE WITH KNOWN OR
POSSIBLY KNOWN RELATIVELY RECENT
CONTACTS -- THE ISLAND IN THE
MEDITERRANEAN OR JEWISH
POPULATIONS.
SO WHAT WE DID IS WE TRIED TO
LOOK AT THE DATA AND FIND A
MODEL OF HISTORY BASED ON
GENETIC FREQUENCY SIMILARITY
THAT WAS CONSISTENT WITH THE
DATA IN OUR RESOLUTION AND I'M
NOT GOING TO DESCRIBE THE
STATISTICAL TESTS TO DETERMINE
THIS MODEL WAS CONSISTENT WITH
THE DATA BUT WE WERE ABLE TO
SHOW THIS MODEL WAS CONSISTENT
WITH THE DATA AS FAR AS WE COULD
TELL.
SO WE STARTED WITH THESE ANCIENT
SAMPLES, THIS 24,000-YEAR-OLD
ANCIENT YOU'RE ASIANS AND THIS
HUNTER GATHERER, AND MORE
DISTANTLY FROM SUB-SAHARAN
AFRICANS, SO FAR SO GOOD.
NATIVE AMERICANS ARE A MIXTURE
OF THESE ANCIENT NORTH YOU'RE
ASIANS, AS I SAID, THEY
CONTRIBUTED TO NATIVE AMERICANS
BUT THEY'RE NOT ALL THE
ANCESTRY, THEY ALSO HAVE
ANCESTRY FROM EAST ASIANS AND
THIS WAS THE MAIN FINDING OF
THAT PAPER BY THIS DANISH GROUP,
NATIVE AMERICANS TODAY SEEM TO
BE CONSISTENT WITH DERIVING FROM
A VERY ANCIENT MIXTURE OF TWO
GROUPS, THERE'S ALWAYS AN IDEA
THAT NATIVE AMERICANS AND EAST
ASIANS ARE SOMEHOW SISTER GROUPS
THAT DESCREND FOR DISAT THAT
PARTICULAR TIMELY FROM WEST
YOU'RE ASIANS BUT IN FACT IT'S
MORE COMPLICATED AND THIS IS A
POTENTIAL RESOLUTION OF THAT.
THE FIRST FARMERS OF EUROPE ARE
A MIXTURE OF AN ANCIENT GROUP
RELATING TO THE HUNTER GATHERERS
OF EUROPE AND ANOTHER VERY
DISTINCT POPULATION THAT'S
ACTUALLY A NEW GHOST POPULATION
WE PREDICT FROM THE DATA, WE'VE
GOTTEN CLOSER TO FINDING THEM
NOW.
WE HAVEN'T QUITE FOUND THEM IN
TERMS OF ANCIENT DNA, AND IT'S A
VERY INTERESTING LINEAGE BECAUSE
IT'S SEPARATED FROM THE AN SES
INVENTORIES OF WEST AND EAST
YOU'RE ASIANS BEFORE THEY
SEPARATED FROM EACH OTHER AND
PEOPLE IN EUROPE TODAY CAN ONLY
BE MODELED AS HAVING MIXTURES
FROM ALL THREE OF THESE SOURCES,
SO WE HAVE A THREE-WAY, NOT A
TWO-WAY MIXTURE.
SO THE MIXTURE PROPORTIONS VARY
DEPENDING ON WHICH EUROPEAN OP
LAITION THEY ARE, BUT ALMOST
EVERYBODY HAS SOURCES FROM ALL
THREE.
SO WHAT ACTUALLY HAPPENED IS THE
ANCIENT DNA HAD SHOWN THE FARMER
HS COME INTO ANCIENT EUROPE, BUT
ALL THE ANCIENT DNA THAT HAD
BEEN STUDIED UP TO THIS TIME HAD
ONLY SHOWN FARMER OR HUNTER
GATHERER ANCESTRY, SO SOMETHING
MUST HAVE HAPPENED TO BRING THIS
ANCIENT NORTH YOU'RE ASIAN
ANCESTRY IN, SO THAT WAS THE
NEXT THING WE DID, WE TRIED TO
ACTUALLY FIND THEY ENTERED
EUROPE.
THE WAY WE STARTED THIS IS IN A
PAPER BASED ON MITOCHONDRIAL DNA
SEQUENCES WHICH LOOKED AT DNA
FROM ABOUT 300 MITOCHONDRIAL --
ARCHEOLOGICAL CULTURES TO FIND
BASED ON THEIR POTTERY DATING
FROM ABOUT 7,500 YEARS AGO TO
ABOUT 3,500 YEARS AGO.
AND THEY START WITH THE FIRST
FARMERS OR EVEN THE HUNTER
GATHERERS AND CONTINUE UNTIL THE
EARLY BRONZE AGE, WHEN PEOPLE
START USING NEW METALS MUCH MORE
WIDELY IN EUROPE.
SO WHAT WE DEVELOPED IS A TEST
OF CONTINUITY, IS IT POSSIBLE
THAT THIS POPULATION, THE SECOND
POPULATION, IS CONSISTENT WITH
DESCENDING DIRECTLY FROM THE
FIRST WITHOUT SUBSEQUENT MIXTURE
AND SO ON.
SO WE HAD A GRID WHERE WE TEST
FOR CONTINUITY FOR EACH OF THE
SUCSUCCESSIVE POPULATIONS, AND
THERE'S A COLORED BOX HERE, WHEN
YOU SEE A LINE OF VERY DARK
COLORED BOXES SHOWING THE HUNTER
GATHERERS ARE CONTINUOUS WITH
ALL THE SUBSEQUENT -- THIS IS
THE EVIDENCE OF FARMERS
REPLACING HUNTER GATHERERS.
IT'S VERY DRAMATIC, BUT AFTER
THE FIRST FARMERS ARRIVE, ABOUT
7500 YEARS AGO IN THIS PART OF
EUROPE, THERE'S CONTINUITY FOR
THE NEXT 2 1/2 TO 3,000 YEARS,
THERE'S NO VERY STRONG EVIDENCE
OF NEW MAJOR INPUT.
BUT THEN BANG, 4500 YEARS AGO,
THERE'S DISCONTINUITY AGAIN,
BEGINNING WITH THE -- CULTURE
AND EVER AFTERWARD THERE'S
DISCONTINUITY.
SO THIS IS A HINT OF WHAT
HAPPENED, THE WAY WE DEALT
WITH -- THE WAY WE EXPLORE THIS
FURTHER IS WE COLLECTED
GENOME-WIDE DATA PLUS ADDITIONAL
INDIVIDUALS, MANY OF THEM FROM
CENTRAL EUROPE, GERMANY, MANY
FROM SPAIN, AND THE WHOLE
IMPORTANT SERIES OF SAMPLES FROM
THE SAMARA REGION OF RUSSIA,
WHICH IS FAR EASTERN EUROPE, AND
IT DATES TO JUST BEFORE THE --
PERIOD.
SO NOW I'M GOING TO ACTUALLY
GIVE YOU A SORT OF STILL MOVIE
OF WHAT HAPPENS OVER TIME IN
EUROPE.
THIS IS THE SAME PICTURE I
SHOWED YOU BEFORE, PRINCIPAL
COMPONENTS ANALYSIS.
REMEMBER HERE IS THE NEAR EAST,
HERE'S EUROPE, I'M NOW GOING TO
GRAY OUT THESE DOTS SO YOU CAN
FOCUS ON THE ANCIENT SAMPLE.
SO HERE'S THE NEAR EAST, HERE'S
EUROPE, AND THE QUESTION; HOW DO
THE ANCIENT SAMPLES FALL
RELATIVE TO PRESENT DAY
POPULATIONS OVER TIME.
SO IF YOU LOOK AT -- HUNTER
GATHERERS FALL BEHIND EUROPE --
WHAT THIS IS SAYING IS THAT ALL
OF THESE HUNTER GATHERERS FROM
SWEDEN HERE, FROM WESTERN EUROPE
HERE AND SPHAI SPAIN AND
LUXEMBOURG
ARE FROM A POPULATION THAT
DOESN'T EXIST IN EUROPE IN
UNMIXED FORM ANYMORE BUT THAT
EUROPEANS TODAY HAVE ANCESTRY
FROM THEM BECAUSE THEY ARE MOVED
AND SHIFTED IN THAT DIRECTION
RELATIVE TO THE NEAR EAST, WHICH
YOU CAN ACTUALLY SHOW FORMALLY
USING MODELING ANALYSIS.
IN THE FAR EAST OF EUROPE, YOU
ACTUALLY HAVE POPULATIONS LIKE
THIS ON THE EUROPEAN -- ON THE
WEST EUR -- ASIAN STEP POINTING
AT THE HIGH END OF THIS GRADIENT
SIMILAR TO THAT ANCIENT NORTH
EURASIAN, AND CARRY THIS
ANCESTRY.
SO EUROPEANS TODAY ARE ON A
GRADE YEPT OF DIFFERENT
PROXIMITY TO -- YOU CAN SEE BOTH
GRADIENTS REPRESENTED HERE, THE
HUNTER GATHERERS RESPONSIBLE FOR
THIS SHIFT AND THE AIN SHEPT
NORTH YOU'RE ASIANS BY THIS
GRADIENT.
SO NOW COMES FARMERS, THERE'S A
LARGE CLUSTER WE HAVE HERE FROM
ALL OVER EUROPE, PRESENT DAY
EUROPEANS EXCEPT FOR SARDINIANS
POSITION IN A PLATE NOT YET
REPRESENTED BY ANY ANCIENT
SAMPLES.
AT THE SAME TIME, WHAT HAPPENS
AFTER THAT IS THE SLIGHTLY LATER
FARMER SHIFLTS SLIGHTLY TOWARDS
THE HUNTER GATHERERS.
THE FARMERS WHO ORIGINALLY
ARRIVED WERE SOCIALLY SEPARATED
FROM THE HUNTER GATHERERS BUT
OVER THE NEXT 2,000 YEARS, THEY
BEGAN TO SPEAK TO THEM.
WE CAN SEE THAT HAPPENING IN
PARALLEL EVERYWHERE.
SIMULTANEOUS WITH THIS IN FAR
EASTERN EUROPE, ANOTHER MIXTURE
OCCURS, PEOPLE FROM THE NORTHERN
NEAR EAST, FROM PLACES LIKE AR
MEAN YA OR RNA AND FORM A MIXED
POPULATION HERE ANALOGOUS TO
THESE MIXED POPULATIONS, BUT AT
THAT TIME, 5,000 YEARS AGO, WE
STILL DON'T HAVE POPULATIONS
LIKE BRITISH PEOPLE TODAY, LIKE
NORTHEAST EUROPEANS, EVEN LIKE
MOST SOUTHERN EUROPEANS.
SO WHEN DOES THAT HAPPEN?
IT HAPPENS 4500 YEARS AGO WITH
THE SUCCEEDING GROUPS.
SUDDENLY THESE GROUPS LIKE THIS
AND THIS MIXED TOGETHER, AND WE
CAN SHOW THESE INFORMAL
STATISTICAL TECHNIQUES THAT IT'S
VERY DIFFICULT TO GET THIS
MIXTURE TO HAPPEN WITHOUT GROUPS
VERY CLOSELY RELATED TO THESE
AND VERY CLOSELY RELATED TO
THESE.
ITS PEOPLE ARE WHAT ARE
CALLED -- THEY ARE HERDING SHEEP
ON THE STEPS.
THEY TOOK THEIR SHEEP OUT ON TO
THE STEP FOR THE FIRST TIME
AFTER DPINNING TO WHEELED
VEHICLES, CARTS AND HORSES,
WHICH ALLOWED THEM TO MOVE OUT
INTO MOBILE HOMES ON TO THE
STEP, AND THEY TOOK ADVANTAGE OF
THIS LANDSCAPE WHICH WAS
UNEXPLOITED BEFORE AND EXPANDED
VERY DRAMATICALLY.
THERE HAD BEEN A CONTROVERSY
ABOUT HOW THEY AFFECTED EUROPE
AND WHAT THE GENETIC DATA SHOWS
IS THAT THEY ACTUALLY HAD A
MAJOR GENETIC IMPACT ON EUROPE
AT THIS TIME.
SO JUST SUMMARIZING THE
POPULATION CHANGES AFTER THE ADD
VENT OF AGRICULTURE, IN EUROPE,
8500 YEARS AGO, THE FIRST
FARMERS LAND IN THE BALKANS IN
GREECE COMING FROM AN ULTIMATE
OR GENERAL JEN IN THE NEAR EAST,
WE HAVE DNA FROM TURKEY WHICH
MATCHES THAT, HYPOTHESES ABOUT
WHERE THEY CAME FROM.
IF YOU WENT TO THE PROPORTION OF
NEAR EASTERN ANCESTRY AND
FARMERS AT THIS TIME, IT'S
APPROXIMATELY 100% MEASURED BY
THIS ORANGE, THE FARMER
INDUSTRY.
IN THE NEXT 2,000 YEARS.
AS THEY MIX, SOCIAL BARRIERS
BREAK DOWN, BUT THERE'S STILL NO
ANCESTRY RELATED TO THE STAFF
AND THAT'S UBIQUITOUS IN EUROPE
TODAY.
THE NEXT THING THAT HAPPENS 45
HUP YEAR4500YEARS AGO, THEY COME
FROM THE
STEPPE AND PEOPLE FROM EUROPE
TODAY, ESPECIALLY NORTHERN
EUROPEANS, MANY OF THEM HAVE AT
LEAST HALF ANCESTRY.
IN MANY EUROPEAN POP PLAITION
LAITIONS -- YOU MAY ASK, BEFORE
I SAID THAT ANCIENT NORTH EUR
ASIANS ARE ONLY A QUARTER OR
EIGHTH OF THE ANCESTRY OF
PRESENT DAY EUROPEANS, BUT
WHAT'S GOING ON IS THE ANCIENT
ARE -- THE YOU'RE ASIANS WERE
TRACER DYE, SO THEY PUT A
MINIMUM ON THE PROPORTION OF
ANCESTRY COMING FROM THE EAST
BUT THEY ACTUALLY BROUGHT A
LARGER PROPORTION OF ANCESTRY IN
AND THIS IS ACTUALLY PROBABLY
THE SINGLE MOST IMPORTANT
CONTRIBUTOR AS LONG AS EARLY
FARMERS TO EUROPEANS TODAY,
THESE PEOPLE.
THIS IS NOT ONLY OUR WORK,
ANOTHER GROUP PUBLISHES AT THE
SAME TIME, THIS DA DANISH GROUP
I
MENTIONED BEFORE CAME TO SIMILAR
COCONCLUSIONS OF A DRAMATIC
TURNOVER IN EUROPE AT THIS TIME.
SO NOW I'M GOING TO EXPAND A
LITTLE BIT MORE BROADLY IN WEST
EURASIA AND TALK ABOUT THE
BROADER WEST EURASIAN CONTEXT IN
EUROPE.
FLOWCIAL SO INTERESTING PLACE
BUT IT'S A BROADER PART OF THIS
BROAD REGION WHERE TODAY PEOPLE
ARE VERY SIMILAR, AS I MENTIONED
AT THE BEGINNING, PEOPLE IN WEST
EURASIA TODAY ARE GENETICALLY
STRIKINGLY SIMILAR.
SO WAS IT ALWAYS THAT WAY?
SO WE JUST PUBLISHED A PAPER A
COUPLE OF MONTHS AGO WHERE WE
GOT DNA FROM 44 ANCIENT SAMPLE
FROM THE ANCIENT NEAR EAST
RANGING FROM 14,000 YEARS AGO TO
4,000 YEARS AGO FROM RNA, FROM
ISRAEL AND JORDAN, FROM AR MEAN
YA, AND THEY INCLUDE PEOPLE FROM
BEFORE THE TRANSITION TO
FARMING, JUST AFTER THE
TRANSITION TO FARMING, THEY
INCLUDE PEOPLE FROM THE EAST OF
THE RENAL AND THEY INCLUDE
PEOPLE FROM THE WEST OF THE
REGION, AND THEY INCLUDE PEOPLE
MOVING INTO THE METAL AGES AND
TO THE COPPER AGE AND THE BRONZE
AGE OVER THIS PERIOD.
SO WHAT WE DID, SO I'M GOING TO
JUST DIGRESS A LITTLE BIT, AND
WHAT MADE THIS ANCIENT DNA WORK
IN THE NEAR EAST POSSIBLE AND I
THINK WHAT'S GOING TO MAKE WORK
IN AFRICA AND SOUTH ASIA
POSSIBLE TOO IS THIS INNOVATION
OF THE PETRUS BONE, A PIECE OF
YOUR TEMPORAL BONE, IT'S THE
PART OF YOUR TEMPORAL BONE
AROUND THE IBER EAR REGION AND
IT HAS BEEN REALIZED IN THE LAST
YEAR OR SO THAT THE PETROUS --
ANY PART OF THE SKELETON THAT
PEOPLE HAVE LOOKED AT.
AND SO ANCIENT DNA SCIENTISTS
HAVE MOVED TOWARDS
PREFERENTIALLY TRYING TO SAMPLE
FROM THE P PETROUS BONE, THAT
COMBINED WITH THIS ENRICHMENT
TECHNIQUE I MENTIONED HAS
INCREASED SUCCESS RATES A LOT.
HEAT IS BAD FOR DNA PREB
PRESENTATION, BUT USING THE
PETROUS -- OTHERS HAVE ALSO HAD
SUCCESSES IN REALLY EXCITING
CONTEXTS.
WE TAKE THESE PETROUS BONES, WE
USE A SANDBLASTER TO REMAY --
CONTAINS A LOT OF THE APPARATUS
OF HEARING, WE GRIND IT, WE MILL
IT, WE OBTAIN POWDER AND SUBJECT
THAT TO LATER DNA PROCESSING.
SO HERE'S THE PICTURE I GAVE YOU
BEFORE BUT WITH MORE SAMPLE, WE
NOW HAVE ANCIENT SAMPLES ACROSS
THIS WHOLE GRADIENT.
WE FIND ANCIENT IRANIANS ARE AT
THE TOP OF THE GRADIENT, SO THEY
DO HAVE DIFFERENT PROPORTIONS OF
ANCESTRY.
IF YOU MEASURE THE LEVEL OF
DIFFERENTIATION OF THE DIFFERENT
GROUPS, IT'S ABSOLUTELY HUGE.
SO IF YOU USE ST:  FST, IT'S
RELATED TO THE SQUARE FREQUENCY
DIFFERENCE BETWEEN PAIRS OF
POPULATIONS, ALL THESE FOUR
POPULATIONS AT THE EXTREMES OF
THE QUADRANT, THE FIRST FARMERS
TO HUNDRED DER GATHERERS OF
WESTERN EUROPE.  IRANIANS AND
THE FIRST FARMERS OF THE WESTERN
PART OF THE NEAR EAST, SO WEST
EURASIA 10,000 YEARS AGO HAS
FOUR GROUPS THAT ARE AS
DISTINCTIVE FROM EACH OTHER AS
EUROPEANS AND EAST ASIANS AND
TODAY WHA WE CAN TRACK IT
THROUGH
TIME.
SO THIS TIME IN THE PAST, 10,000
YEARS AGO, THE DIFFERENCE IS AS
LARGE AS EUROPEANS AND EAST
ASIANS, SO WHAT HAPPENED?
10,000 OR SO YEARS AGO, YOU HAVE
THESE FOUR APPROXIMATE SOURCES
OF ANCESTRY IN WESTERN EURASIA,
EASTERN HUNTER GATHERERS AND
GROUPS RELATED TO THEM, FIRST
FARMERS FROM THE WESTERN NEAR
EAST, FIRST FARMERS FROM THE
LATER NEAR EAST, THEY MIXED
DRAMATICALLY AND THE REASON
DIFFERENTIATION AMONG THE GROUPS
TODAY IS SOLO IT'S BECAUSE OF
THE MIXTURE, BECAUSE THEY'VE ALL
MIXED WITH EACH OTHER.
SO THE NEAR EASTERN FARMING
EXPANSION AND ITS AFTER EFFECTS
HOMOGENIZED -- TO A REGION OF
BROAD HOMOGENEITY WHICH LOOKS SO
SIMILAR TODAY AND A LOT OF
PEOPLE SORT OF IMAGINE IT'S
ANCIENT BUT IN FACT IT'S A VERY
RECENT PHENOMENON.
HYPOTHESIS IS THAT EAST ASIAN
AND AFRICAN AGRICULTURAL
EX-PAPTIONS MAY HAVE SIMILARLY
HHOMOGENIZE THOSE CAT TBRIS WE
HAVE IN OUR HEAD, BUT THERE'S NO
ANCIENT DNA THAT'S COMPARABLE TO
WHAT'S IN EUROPE YET.
THE FINAL PART OF MY TALK, I
WANTED TO TALK ABOUT THE INSIGHT
ABOUT BIOLOGY THAT ARE COMING
FROM ANCIENT DNA AND STUDIES OF
MODERN DNA THAT RELATED TO --
AND THAT I THINK ARE EXCITING.
SO FIRST I INTRODUCE THE IDEA OF
A SELECTIVE SWEEP, WHEN A SINGLE
MUTATION OCCURS IN A PERSON
THAT'S ADVANTAGEOUS THAT MIGHT
ALLOW YOU TO DIGEST COW'S MILL
NOOK ADULTHOOD, FOR EXAMPLE, IF
COW'S MILK IS AVAILABLE AS A
SOURCE OF NUTRITION, IT OCCURS
IN ONE PERSON AND THEN THE IDEA
IS THAT IT RISES TO HIGH
FREQUENCY IN A POPULATION UNDER
THE PRESSURE OF NATURAL
SELECTION.
THAT'S WHAT'S CALLED A SELECTIVE
SWEEP AND IT'S REALLY EASY TO
DETECT USING GENETIC PATTERNS
BECAUSE WHAT HAPPENS AROUND THE
SELECTIVE SWEEP IS EVERYBODY
DESCRENDZ FROM THAT INDIVIDUAL
WHO HAS THAT MUTATION PRETTY
RECENTLY IN TIME, AND THAT
LEAVES A SCAR IN THE GENOME AND
THE PATTERN OF VARIATION IS EASY
TO DETECT.
SO HERE'S AN EXAMPLE IF YOU
SCREEN ACROSS THIS CHROMOSOME
2 AND LOOK FOR PLACES IN THE
GENOME THAT HAVE STRONG
REDUCTION IN VARIATION MEASURED
IN ONE WAY OR ANOTHER, YOU'LL
SEE A BIG PEAK THAT ALLOWS YOU
TO ADJUST COW'S MILK INTO
ADULTHOOD.
BUT ACTUALLY MOLLY AND
COLLEAGUES SHOWED -- HAVE SHOWN
THAT, IN FACT, SELECTIVE SWEEPS
ACTUALLY ARE RELATIVELY RARE IN
HUMAN EVOLUTION, THERE'S A LOT
OF EVIDENCE FOR NATURAL
SELECTION BUT SELECTIVE SWEEPS
HAVE NOT DRIVEN MOST OF IT.
INSTEAD MOST OF IT SEEMS LIKELY
TO BE SELECTION ON PRE-EXISTING
VARIATION IN THE POPULATION THAT
SUDDENLY UNDER A NEW
ENVIRONMENTAL CONDITION BECOMES
ADVANTAGEOUS, AND THAT WON'T
LEAVE A SCAR IN THE GENOME.
SO IN A WAY WE'RE ONLY FINDING
WHAT WE CAN EASILY FIND.
THE LOW HANGING FRUIT, WE'RE NOT
ACTUALLY FINDING MOST OF WHAT
MATTERS.  SO WHAT WE ACTUALLY
DID WITH OUR ANCIENT DNA DATA IS
WE TOOK ADVANTAGE OF THE FACT
THAT IT GIVES YOU TIME SERIES
DATA.
WE UNDERSTAND AS EXPERIMENT
LISTS THE POWER OF BEING ABLE DO
AN EXPERIMENT AND WATCH THEM
DEVELOP OVER TIMES BUT IN HUMAN,
UNTIL ABE SHENT DNA, WE HAD TO
BE STUCK WITH PEOPLE IN THE
PRESENT DAY AND WE HAVEN'T BEEN
ABLE TO WATCH HOW PEOPLE EVOLVE
INTO EACH OTHER -- SO WHAT WE
CAN DO WITH ANCIENT DNA IS WATCH
FOR EXAMPLE EUROPEAN POPULATION
AND HOW THEY CHANGE OVER TIME,
SO WHAT WE DID IS TOOK THIS
MODEL FIT INTO THE DATA OF
EUROPEANS TODAY BEING A MIXTURE
OF THREE HIGHLY DIFFERENT
ANCESTRAL POPULATIONS AND THEN
WE TOOK EACH POSITION IN THE
GENOME WHEN WE ASKED DOES THAT
POSITION IN PRESENT DAY
EUROPEANS FROM DIFFERENT
POPULATIONS HAVE THE FREQUENCY
YOU WOULD EXPECT BASED ON THE
WHOLE GENOME.
SO WE RUN THIS ACROSS THE GENOME
GENOME, NOT FOR AFFECTING
DIABETES OR NOT BUT WHETHER IT'S
CHANGED IN FREQUENCY MORE THAN
YOU'D EXPECT BY CHANCE AND WE
FIND AT LEAST 12 GENOME-WIDE
SIGNIFICANT LOCATIONS WITH THE
DATA THAT WE HAD AVAILABLE AT
THE TIME THAT WE DID THIS SCAN.
SOME OF THEM ARE KNOWN
VARIATIONS AND SOME OF THEM ARE
ONES THAT HAVE NOT BEEN
IDENTIFIED BEFORE.
I'LL GIVE YOU A FEW EXAMPLES SO
THIS IS LAC LACTASE -- IN ALL
SAMPLES RANGING FROM ABOUT 8,000
TO 4,000 YEARS AGO, IT'S VERY
RARE, AND TODAY IN NORTHERN
EUROPEANS, IT'S VERY COMMON, SO
YOU CAN SEE WHY THERE'S VERY
STRONG EVIDENCE THAT HAS CHANGED
IN FREQUENCY AND REALLY IT ONLY
BEGINS TO BE SEEN IN EUROPE
ABOUT 4,000 YEARS AGO.
SIMILARLY FOR LIGHT SKIN, LIGHT
SKIN IS LOWER IN FREQUENCY IN
ALL OF THESE ANCIENT POPULATIONS
THAT INCLUDE THE SOURCES OF
NORTHERN EUROPEANS THAN IT IS IN
NORTHERN EUROPEANS TODAY AND
EVEN IN SOUTHERN PURE PEENS, THE
MAIN VARIANTS AFFECTING LIGHT
SKIN SEEM TO HAVE COME IN FROM
THE MOST PART FROM THE ANCIENT
NEAR EAST WITH THE FARMERS.
BLUE EYE COLOR IS REALLY FROM
THE INDIGENOUS HUNTER GATHERERS
OF EUROPE AND THERE SEEMS TO
HAVE BEEN REPEATED TYPES OF
SELECTION ON THIS VAIR YAPT.
FOR US THIS WAS NOT THE MOST
EXCITING TYPE OF WORK, FOR ME
THE MOST EXCITING TYPE OF WORK
WAS THE GENETIC -- OUR ABILITY
TO LOOK AT THIS DATA AT
SELECTION FOR COMPLEX TRAITS,
FOR THINGS THAT ARE NOT
UNDERPIBBED BY A SINGLE GREEN
BUT MANY GENES, SO WHERE WE HAD
OUR MOST SUCCESS IN THIS AREA
AND WHAT I'M MOST EXCITED ABOUT
FOR THE FUTURE IS IN THE CASE OF
HEIGHT, SO HEIGHT IS A TRAIT
THAT'S BEEN STUDIED IN HUNDREDS
OF THOUSANDS OF PEOPLE NOW IN
MEDICAL GENOME-WIDE ASSOCIATION
STUDIES, SO WE'VE ANNOTATED AS A
COMMUNITY MILLIONS OF POSITIONS
IN THE GENOME FOR HOW THEY
AFFECT PEOPLE'S HEIGHT.
SO WE HAVE THIS ANNOTATION THAT
WE CAN THEN CORRELATE TO CHANGES
IN FREQUENCY OVER TIME.
SO THERE'S CLEARLY A GENETIC
UNDERPINNING TO HEIGHT IN
EUROPE, THE ORDER IN WHICH
POPULATIONS OF ORDER BY HEIGHT
HAS REMAINED THE SAME WITH
RELATIVE SMALL STATURE IN
PORTUGAL, HIGH STATURE IN
CROATIA AND NETHERLANDS, FOR
EXAMPLE, AND THAT'S CHANGED OVER
TIME -- THAT'S REMAINED CONSTANT
OVER TIME.
IN 2000, LANGO-ALLEN AND
COLLEAGUES PUBLISHED A VERY
IMPORTANT PAPER WHERE THEY FOUND
180 INDEPENDENT POSITIONS IN THE
GENOME THAT AFFECTS PEOPLE'S
STATURE.
A LATER PAPER BY JOEL -- FOWNDZ
THERE'S SELECTION FOR DIFFERENT
STATURE, THEY FOUND CONSISTENT
EVIDENCE THAT THE VARIANTS
AFFECTING TALLER STATURE, LARGER
STATURE, WERE MORE COMMON IN
NORTHERN THAN IN SOUTHERN
EUROPEANS AND THAT THIS WAS TOO
MUCH TO BE EXPLAINED BY RANDOM
FLUCTUATION SO MUST HAVE BEEN
CALL FOR SMALLER OR TALLER BUT
THEY DIDN'T KNOW WHICH.
SO WE HAD ANCIENT DNA FROM EACH
OF THESE ANCIENT POPULATIONS AND
WE COULD SCORE THEM FOR WHETHER
THEY HAD -- WHAT THEIR PREDICTED
HEIGHT WAS BASED ON THE GENETIC
VARIANT THAT FROM PRESENT DAY
GENOME WIDE ASSOCIATION STUDIES,
NO AFFECT IN HEIGHT.
SO AS POPULATIONS MOVE INTO THE
MIDDLE OF THE FIRST FARMING
PERIOD, THERE EMERGES A DIRNS
BETWEEN NORTHERN EUROPEAN
FARMERS AND SOUTHERN EUROPEAN
FARMERS AND THERE'S A
STATISTICALLY SIGNIFICANT DROP
IN GENETICALLY PREDICTED STATURE
IN SOUTHERN EUROPEANS.
SO WHAT THIS MEANS IS THAT THE
REDUCED STATURE IN SOUTHERN
EUROPE IS ACTUALLY DO AND DRIVEN
IN LARGE PART BY SELECTIONS TO
REDUCE STATURE, THERE'S A
SEPARATE EFFECT IN THE STEP
WHERE THERE SEEMS TO HAVE BEEN
SELECTION TO PROBABLY INCREASE
STATURE IN THE STEPPE, THESE
PEOPLE COME IN TO EUROPE 4500
YEARS AGO.
THAT'S WHAT'S GOING ON, THAT'S
WHAT'S EXPLAINING IT.
IT'S NOT CLEAR WHY TALLER OR
SHORTER STATURE WOULD HAVE BEEN
FAVORED IN CERTAIN ENVIRONMENTS
AND SO I THINK THAT THIS IS
REALLY AN EXCITING WAY TO
INTERROGATE HOW TRAITS EVOLVE
OVER TIME, AND I THINK IT
COMBINES THE POWER OF
GENOME-WIDE ASSOCIATION STUDIES
WHICH HAVE NOW BEEN CARRIED OUT
FOR MANY TRAITS, DIABETES AND
HEART DISEASE AND MANY CANCERS
AN AUTOIMMUNE DISEASES AS WELL
AS HEIGHT AND OTHER TRAITS,
WHICH HAVE RURLTE RESULTED IN
ANNOTATIONS OF THE GENOME, OFTEN
THEY'RE VERY, VERY MINOR EFFECTS
BUT WE CAN CORRELATE THEM TO
CHANGES IN FREQUENCY OVER TIME
TO SEE WHETHER THERE'S BEEN
SELECTION IN ONE WAY OR ANOTHER
WITH CERTAIN TRAITS.
HEIGHT IS THE BEST UNDERSTOOD
TRAIT BUT THE PAPER BY JONATHAN
PRITCHARD'S GROUP THAT'S ON A
PRE-PRINT SERVER AND I HOPE WILL
BE PUBLISHED SOON FINDS
EVOLUTION NOT JUST OF HEIGHT,
WHICH IS A STRONG SIGNAL, BUT OF
INFANT HEAD CIRCUMFERENCE AND
INSULIN LEVELS, AGE OF PUBERTY,
ESPECIALLY IN FEMALES, YOU CAN
SEE EACH OF THE TRAITS IN
BRITAIN WHERE THE STUDY IS BASED
IN THE LAST 2,000 YEARS IN THE
SAME TYPE OF WAY, BY CORRELATING
CHANGES IN FREQUENCY INFERRED
FROM GENETIC DATA WITH THE
ANNOTATIONS FROM GENOME-WIDE
ASSOCIATION STUDIES.
SO I WANT TO FINALLY CONCLUDE BY
ASKING THE QUESTION, IF YOU GO
BACK IN TIME, HOW MODERN TRAITS
APPEAR SO I'M GOING TO GIVE YOU
A LITTLE BACKGROUND ON THIS.
FIRST ANATOMICALLY MODERN
HUMANS, PEOPLE WITH SKELETONS
SIMILAR TO HOURS DATED ALMOST
200,000 YEARS AGO IN EAST
AFRICA, AND THE ARCHEOLOGICAL
STUDIES OF THESE PEOPLE, THE
STONE TOOLS THEY MADE, THE
ORNAMENTS THEY LEFT BEHIND,
INDICATE THERE HAVE NOT -- THAN
THEIR CAN YOU SIPS IN EUROPE, OR
ELSEWHERE IN ASIA OR ELSEWHERE
IN AFRICA.
THAT IS, THESE PEOPLE WERE
ANATOMICALLY LIKE US BUT THEY
WERE BEHAVIORALLY JUST LIKE
NEANDERTHALS AND MADE SIMILAR
TOOLS, AND IT TOOK 150,000 YEARS
FOR THESE PEOPLE TO ACTUALLY
BECOME BEHAVIORALLY MUCH MORE
LIKE US.
ARC LOGICALLY THERE'S DOCUMENTED
ABOUT 50,000 YEARS AGO A
QUICKENING OF ARCHEOLOGICAL
CHANGE WHERE MUCH MORE COMPLEX
TOOLS START TO BE MADE INCLUDING
BONE TOOLS, NOT JUST STONE
TOOLS, LEFT BEHIND, EVIDENCE OF
CLEARING, ORNAMENTATION,
DELIBERATE BURIALS, ALL OF THESE
OCCURRED AT SOMETIME BEFORE BY
PERHAPS NOT AS INTENSE.
WHAT YOU'RE ACTUALLY SEEING HERE
IS EVIDENCE OF GREAT CHANGE IN
THE HUMAN POPULATION AND PERHAPS
IT'S EVEN A BIOLOGICAL CHANGE,
MAYBE THERE'S BEEN A GENETIC
SWITCH, A CHANGE MAYBE IN
NEUROLOGICAL GENE THAT WOULDN'T
HAVE LEFT AN IMPRINT IN THE
BRAIN CASE BUT ROSE TO HIGH
FREQUENCY AND ALLOWED COMPLEX
BEHAVIORAL -- MAYBE LANGUAGE AND
THAT POPULATION EXPANDED LARGELY
DISPLACING ALL THE PEOPLE WHO
WERE THERE, THEY PROBABLY
EXPENDED WITHIN AFRICA TOO,
DISPLACING MOST OF THE
POPULATIONS THAT WERE THERE,
THAT WAS THE IDEA THAT WAS VERY
ECEXCITING.
THIS IDEA OF A GENETIC CHANGE
THAT MIGHT EXPLAIN FROM OUR
RELATIVES HAS BEEN INVOKED BY A
LOT OF PEOPLE, INCLUDING ME, TO
JUSTIFY SIR CHS FOR EVOLUTIONARY
STUDIES, OR WE'RE GOING TO FIND
THE KEY TO WHAT MAKES US
SPECIAL, BY SEQUENCING THE
DIFFERENCES BETWEEN US AND
CHIMPANZEES, WE'RE GOING TO READ
IT LIKE A BOOK AND FIGURE OUT
WHAT MAKES US SPECIAL.
THE PROBLEM IS, WE STILL HAVEN'T
FIGURED OUT ANYTHING ABOUT
WHAT'S SPECIAL, EVEN THOUGH
THEY'VE RESULTED IN SUCH AMAZING
SUCCESSES IN OTHER WAYS.
SO WHAT I WANT TO CONCLUDE ON IS
SOME WORK THAT SPEAKS TO SOME OF
THESE QUESTIONS, THIS PAPER THAT
FRANCIS REFERRED TO JUST BEFORE,
WHICH IS A STUDY WE JUST
PUBLISHED OF 300 HIGH QUALITY
GENOME SEQUENCES FROM
142 DIVERSE POPULATIONS FROM
PLACES SHOWN IN THIS MAP AND
CONTAINS A LOT OF RESOURCES
ESPECIALLY FROM POPULATIONS THAT
HAVE NOT BEEN SAMPLED BEFORE,
FOR EXAMPLE, SOME POPULATIONS
FROM AFRICA OR NEW GUINEA AND
ELSEWHERE.
THE FIRST THING THAT WE CAN DO
IS WE CAN LINE UP THE GENOME
SEQUENCES FROM THE MOTHER AND
FATHER, COUNT THE NUMBER OF
DIFFERENCES BETWEEN THEM, AND
THEY PROVIDE A MEASURE OF TIME.
SO WE CAN ASK HOW LONG HAS IT
BEEN SINCE THE WERE -- AND YOU
CAN COMPARE TWO POPULATIONS TO
EACH OTHER AS WELL, AND SO WHAT
WE'VE DONE IS WE'VE USED THE
TECHNIQUE DEVELOPED BY ANOTHER
GROUP FOR ESTIMATING POPULATION
SEPARATION, AND FOR MANY PAIRS
OF POPULATION, MUCH OF THE
SEPARATION HAPPENED BEFORE
50,000 YEARS AGO, WHICH IS WHEN
THIS GREAT CHANGE OCCURS.
SO THE FIRST THING TO KEEP IN
MIND IS THAT THESE BIG CHANGES
THAT DOCTORS OCCURRED HAPPENED
BEFORE THE SEPARATION OF A LOT
OF PRESENT DAY POPULATION SO IF
YOU BELIEVE THAT THERE WAS A BIG
CHANGE, IT MUST HAVE OCCURRED
MORE IN THE ANCESTRY BUT ALMOST
ALL POPULATIONS TODAY ARE
CAPABLE OF FULLY --
>FULLY --THE SECOND
RESULT, WE USED THE SAME
TECHNIQUE TO ESTIMATE AT EACH
FIRST PLACE IN THE GENOME HOW
FAR BACK IT IS, BUT JUST
COUNTING DENSITY MUSHARRAF
TAITIONS.
SO THIS IS A RESULT ON A
CHROMOSOME FOR PERSON ONE, IS
HOW FAR BACK IN TIME DO THE TWO
CHROMOSOMES SHARE A COMMON
ANCESTRY?
HOW FAR BACK IN TIME DO WITH
VERY TO GO FOR EVERYBODY -- THE
ANSWER IS THERE'S REALLY NOWHERE
IN THE GENOME WHERE SOMEBODY
SHARES SL -- MOST OF IT WE'VE
COVERED.
AND IF YOU BELIEVE THIS GENETIC
SWITCH IDEA, YOU MUST BELIEVE
THERE'S A GENETIC -- ROSE HIGH
FREQUENCY BY ABOUT 50,000 YEARS
AGO, AND THEN EVERYBODY TODAY.
BUT THAT'S NOT WHAT WE SEE AT
ALL, THERE'S NOTHING EVEN
PLAUSIBLY CLOSE TO THAT, SO THE
CONCLUSION OF THIS PART OF THE
TALK IS THAT I THINK THAT FOR
ME, IT'S SUGGESTING THAT THERE'S
NOT LIKELY TO BE SIMPLE
EXPLANATIONS FOR BEHAVIOR,
EVOLUTION OF THESE BEHAVIORALLY
COMPLEX TRAITS THAT ARE EVIDENT
IN THE ARCHEOLOGICAL RECORD AND
MAYBE YOU MIGHT GENERALIZE MORE
BROADLY IF THERE MIGHT NOT BE
SIMPLE EVOLUTIONS OF HUMAN
TRAITS.
WE DON'T THINK THERE HAVE BEEN
ANY EVIDENCE IN ENABLING
MUTATION BUS SUDDENLY APPEARED
AND ALLOWED THEM TO THINK THAT
IT WAS SOMEHOW A POPULATION,
WHAT WE CALL A MUTATION LIMITED
STATE, WHICH COULD DO THINGS
BEFORE AND THEN SUDDENLY AN
AMAZING MUTATION HAPPENED THAT
ALLOWED PEOPLE TO DO THINGS
BECAUSE WE DON'T SEE ANY
EVIDENCE IN THE MUTATION THAT IT
COULD HAVE BEEN LIKE THAT.
I THINK THAT DISTINCTTIVELY
HUMAN BEHAVIOR BECAUSE OF THIS,
IT SEEMS MORE LIKELY TO BE A
COMPLEX TRAIT, NOT LIKE SKIN
COLOR OR LACTASE PERSISTENCE,
THAT HUMAN POPULATIONS BEFORE
WITH THEM NECESSARY TO DO
EVERYTHING WE DO AND IT SEEMS IN
THIS CONTEXT THAT MAYBE
ENVIRONMENTAL AND CULTURAL
CHANGES WHICH PERHAPS -- LIKELY
TO HAVE BEEN DRIVERS OF GREAT
CHANGES THAT OCCURRED, AND IT'S
AN INTERESTING CASE HERE WHERE
GENETICISTS SEARCH WHERE
GENETICS IS THE EXPLANATION BUT
HERE IN A SORT OF PARADOXICAL
WAY, GENETIC -- WHAT MAKES US
SPECIAL OR DIFFERENT, BUT I
ACTUALLY THINK THAT'S AN
OPPORTUNITY IN A WAY BECAUSE I
ACTUALLY THINK THAT THE
INTERESTING INSIGHTS WILL COME
FROM TRYING TO EMBRACE THE
COMPLEXITY RATHER THAN TO COME
UP WITH A SIMPLE EXPLANATION, SO
THAT'S THE END OF MY TALK AND I
THINK THERE'S TIME FOR A FEW
QUESTIONS.
[APPLAUSE]
>> THANKS, DAVID, THAT WAS
FASCINATING INDEED AND I SUSPECT
PEOPLE DO HAVE QUESTIONS.
PLEASE USE THE MICROPHONE SO
THAT PEOPLE LISTENING ON THE
VIDEO CAN ALSO HEAR THE
QUESTION.
PLEASE START RIGHT HERE.
>> I'M WONDERING ABOUT DISEASE
CORRELATIONS AND WITH YOUR
PATTERNS OF THE THREE OR FOUR
EUROPEAN BACKGROUNDS, IS THERE
ANY LINKAGE TO ANY PARTICULAR
DISEASES, IN OTHER WORDS, CAN
YOU SAY THAT SOME DISEASES,
GENETIC DISEASES ORIGINATED IN
THOSE DIFFERENT POPULATIONS?
>> THE QUESTION IS WHETHER
CERTAIN DISEASES ARE LIKELY TO
HAVE ORIGINATED IN ONE
POPULATION OR THE OTHER.
WE IN FACT TRY TO LOOK AT THE
GENOME-WIDE ASSOCIATION CATALOGS
AND CORRELATE THEM TO DIFFERENT
CONTRIBUTIONS IN ONE WAY OR THE
OTHER AND WE HAVEN'T REALLY
OBTAINED ANY ADEQUATE RESULTS IN
THAT WAY EXCEPT FOR HEIGHT YET.
I THINK IT'S IN PART DUE TO THE
LIMITATION OF THE ANCIENT DNA
DATA WE HAD AVAILABLE AT THE
TIME.
THIS WAS DRIVEN BY SAMPLE SIZE,
SO I THINK IN ORDER TO OBTAIN
BETTER INSIGHT, WHAT WE WANT TO
DO IS INCREASE THE SAMPLE SIZE
AND THAT'S HAPPENING VERY
RAPIDLY NOWP, SO I THIN NOW, SO
I THINK
COMBINING THE ANCIENT DNA DATA
WITH THE -- WE MIGHT BE ABLE TO
PARTITION DISEASES IN THIS WAY.
>> AT THE BEGINNING OF THE TALK,
I GOT THE IMPRESSION THAT THE
ENRICHMENT METHODS WERE YOU
USING, WERE YOU SAMPLING
ACTUALLY A VERY SMALL FRACTION
OF THE GENOME BUT GETTING LOTS
OF COVERAGE OF IT.
WHEN YOU USE THE PHRASE
GENOME-WIDE, DOES THAT MEAN JUST
THAT ENRICHMENT OR DO YOU
LITERALLY MEAN ATTEMPTING TO GET
THE ENTIRE GENOME, AND THEN
COMING LATE IN THE TALK WHEN YOU
TALKED ABOUT YOUR 300 GENOME,
AGAIN, WHAT FRACTION OF THE
GENOME IS BEING SAMPLED?
>> RIGHT.
SO THE GENOME-WIDE DATA, WHAT
WE'RE USING IN OUR LABORATORY IS
AN ENRICHMENT TECHNIQUE THAT
DOESN'T SEQUENCE THE WHOLE
GENOME FOR MOST SAMPLES.
WE SOMETIMES SEQUENCE THE WHOLE
GENOME BUT WE ENRICH BASICALLY
ABOUT 1.2 MILLION POSITIONS THAT
ARE OF INTEREST.
FOR -- IT'S ONLY A% OF POSITIONS
5% OF -- 
BUT
THE MEDIAN MIGHT BE .3 AND MANY
SAMPLES ARE HEAVILY COVERED AT
THOSE POSITIONS BUT NOT EVERY
POSITION IN THE GENOME AND
THAT'S THE SECRET WE'VE USED FOR
VERY LARGE NUMBER OF SAMPLES.
THERE IS A POSSIBLE THING ONE
COULD DO, WHICH WOULD BE TO
SHOTGUN DEEP SEQUENCE A LOT OF
THESE SAMPLES AMENABLE TO IT
BECAUSE THEY HAVE HIGH
PERCENTAGE OF HUMAN DNA.
THAT IS NOT WHAT WE HAVE DONE ON
THESE SAMPLES SO FAR, IT'S --
THE LAST QUESTION YOU ASKED WAS
ABOUT THE 300 GENOMES, THAT'S
PRET DAY GENOMES TO --
>> JUST ONE LAST QUESTION WHEN
YOU SHOWED THE MOORE'S LAW OF
GROWTH OF APRIL SHENT DNA
SEQUENCES IN GENERAL FROM MANY
INVESTIGATORS, IN GENERAL, ARE
MOST OF THOSE SEQUENCES LIKE
YOUR, JUST SAMPLING SOME SMALL
PERCENT OF THE GENOME, OR ARE
ANY OF THOSE A LARGER --
>> OUR LABORATORY HAS PRODUCED
MORE THAN HALF OF THE SEQUENCES
PUBLISHED TODAY, SO MOST OF THEM
PUBLISHED ARE FROM THAT
TECHNIQUE.
BUT A SUBSTANTIAL FRACTION ARE
SHOTGUN SEQUENCE DATA.
>> THE GRANTS FROM PRINCETON HAD
DONE STUDIES OVER SEVERAL
DECADES LOOKING AT DARWIN'S,
FINCH, LOOKING AT -- NOTICE
THERE'S AN EVOLUTION OF PEAK
SIZE BASED ON ENVIRONMENTAL
IMPACT.
I'M JUST CURIOUS TO KNOW IF YOU
LOOK AT THE PARTICULAR POINT IN
TIME WHERE YOU SEE THE DIFFERENT
GROUPINGS, DO THEY MERGE AND IS
THERE SORT OF A BLENDING AND AT
TIMES OF GEOLOGICAL STRESS?
AND THEN ANOTHER QUESTION I HAD
HAD TO DEAL WITH WHETHER OR
NOT -- LIKE YOU MENTIONED THE
LACTOSE AND ABILITY TO DIGEST
MILK.
ARE THERE GENE DRIVERS
ASSOCIATED WITH THAT SO THAT IT
BECOMES MORE AND MORE PREVALENT
WITHIN A POPULATION?
>> SO -- YEAH, SO I THINK AGAIN
WE'RE AT THE POINT WHERE WE
DON'T HAVE ENOUGH ANCIENT DNA
YET.
MOST OF OUR ANCIENT DNA IS FROM
A RELATIVELY NARROW TIME SLICE
THAT I REPORTED ON, BETWEEN
ABOUT 7,000 YEARS AGO AND ABOUT
4,000 YEARS AGO.
AND SO IN ORDER TO REALLY CLOCK
EUMENDOCUMENT, I WOULD WANT TO
FILL
IN A MORE RECENT PERIOD AND
ALLOW ONE TO TRACK EXACTLY WHEN
THE CHANGES OCCUR.
IN SOME APPROXIMATION, WE HAVE
TWO TIME POINTS, THE FIRST
FARMERS AND THEIR IMMEDIATE
SUCCESSORS IN EUROPE AND THE
PRESENT.
SO THAT'S 2 POINTS AND WE CAN'T
REALLY DO MORE THAN DRAW VOLUME
CONNECTING THOSE TWO-POINT, BUT
WITH MORE DATA, WE CAN ACTUALLY
FILL IN THAT LINE AND FIGURE
OUT -- WITH LACK TASTE
PERSISTENCE, YOU CAN ACTUALLY
SEE IN OUR DATA, YOU CAN SEE THE
FIRST OCCURRENCES AND
SUBSTANTIAL FREQUENCY ABOUT 4 OR
5,000 YEARS AGO.
YOUR OTHER QUESTION?
>> HAD TO DO WITH GENE DRIVERS.
I'M JUST WONDERING, YOU HAVE A
MUTATION AND THEN IT SEEMS TO
BECOME MORE PREVALENT IN A
POPULATION SUCH AS LACTOSE
INTOLERANCE.
AND I'M WONDERING, IS THERE
SOMETHING THAT'S DRIVING THAT
PREVALENCE?
>> MY GUESS, I DON'T KNOW, BUT I
THINK WHAT WE KNOW -- I THINK
WHAT WE GENERALLY ASSUME IS THAT
THE INCREASE IN FREQUENCY OF
LACTOSE PERSISTENCE IS DRIVEN BY
THE -- OF MILK, SO PEOPLE HAVE
MORE OFFSPRING IF THEY ARE ABLE
TO DO THAT, SO IT'S JUST NATURAL
SELECTION.
I DON'T THINK WE HAVE ANY
EVIDENCE, BUT I'M NOT SURE I'M
ANSWERING THE QUESTION.
>> YOU MENTIONED YOU'RE LOOKING
AT A SPECIFIC JEAN, AB YOU'RE
NOT LOOKING AT WHAT MAY BE
ASSOCIATED WITH THAT GENE, IS
THAT CORRECT?
>> THAT'S RIGHT.
THERE'S A LOT TO DO.
>> YOU MENTIONED THE NARROW TIME
SLICE OF SAMPLES YOU'RE LOOKING
AT.
IS THERE ANY POSSIBILITY YOU CAN
COMPARE YOUR SAMPLE AND IN
PARTICULAR THE GHOST POPULATION
TO EXISTING OLDER ANCIENT --
BEYOND THE TALL GENOME AND THEN
IT'S OPEN TO SEE IF THOSE IN ANY
POSSIBLE WAY ARE RELATED TO --
>> YEAH, I'VE DONE A LOT OF
WORK, MOST OF MY WORK IN ANCIENT
DNA AND THE RELATIONSHIPS
BETWEEN THESE GROUPS.
UP WITH THING THAT WE CAN SEE,
AND IT'S ACTUALLY IN THIS WORK
ON THE NEAR EAST, WE CAN
ACTUALLY SEE THERE'S BEEN --
ACTUALLY ANOTHER PAPER WE
PUBLISHED A FEW MONTHS AGO WHICH
WAS ON UPPER -- EUROPE SO
EUROPEANS, 51 SAMPLES BETWEEN
45,000 AND 7,000 YEARS AGO IS
THAT THERE'S ACTUALLY BEEN A
DECREASE IN NEANDERTHAL ANCESTRY
OVER TIME IN EUROPE SO THAT IN
THE FIRST EUROPEAN MODERN
EUROPEANS WE HAVE DATA FROM OR
YOU'RE ASIAN, IT'S ABOUT 5% AND
DECREASES TO ABOUT 2% TODAY, SO
THERE WAS MORE NEANDERTHAL
ANCESTRY IN THE PAST, AND IT'S
ACTUALLY INTERESTING BECAUSE
THESE POPULATIONS ARE DIRECTLY
ANCESTRAL TO SOME OF THE LATER
POPULATIONS SO WE THINK THERE'S
BEEN NATURAL SELECTION TO REMOVE
NEANDERTHAL ANCESTRY, IT'S
SLIGHTLY DISADVANTAGEOUS BUT WE
CAN ACTUALLY TELL VERY
ACCURATELY WHETHER THE
PROPORTION OF AN SES TREES IN
INDIVIDUAL GENOME -- NONE OF
THESE GROUPS HAVE EXTREMELY
LARGE AMOUNTS EXCEPT FOR ONE
SAMUEL FOUND, WHICH HAD ABOUT
10%, AND WE FOUND THAT -- WAS A
NEANDERTHAL SO WE'RE VERY LUCKY
WE FOUND A 40,000-YEAR-OLD
INDIVIDUAL LIKE THIS.
BUT MOST OF THESE SAMPLES ARE
MUCH LESS AND NOT PARTICULARLY
UNUSUAL FOR THEIR TIME.
>> DAVID, LET ME ASK YOU ABOUT
WHAT YOU PERCEIVE AS THE
MATURITY OF THIS VERY RAPIDLY
MOVING FIELD.
AMAZING OBSERVATIONS THAT HAVE
COME FORWARD IN JUST THE LAST
FEW YEARS, BUT WHAT DO YOU THINK
IS GOING TO HAPPEN IN THE NEXT
HALF DECADE?
ARE THERE MANY MYSTERIES YET TO
BE REVEALED, OR IS THE BIG
PICTURE NOW PRETTY MUCH TAKING
SHAPE?
>> THANK YOU.
I THINK THAT WE'RE REALLY JUST
AT THE BEGINNING.
THERE ARE SO MANY THINGS TO DO
SO I CAN JUST RATTLE OFF A
SERIES OF THINGS ONE IN
PRINCIPLE CAN DO.
WE COULD INCREASE SAMPLE SIZE
TREMENDOUSLY AND NOW THAT'S VERY
EASY AND WE CAN ACTUALLY REALLY
STUDY NATURAL SELECTION WITH
REALLY HIGH STATISTICAL POWER.
THE STUDY I TOLD BUT WAS JUST A
PROOF OF PRINCIPLE, BUT THERE'S
REALLY THE POSSIBILITY OF REALLY
DOING THIS WITH EXTRAORDINARY
ACCURACY OF DOING SCANS OF WHAT
NATURAL SELECTION LANDSCAPE WAS
LIKE 10,000 YEARS AGO AND
COMPARING IT TO THE PRESENT,
SELECTION CHANGE AND ITS NATURE.
ANOTHER POSSIBILITY IS TO STUDY
WHAT HAPPENED AFTER THE BRONZE
AGE IN EUROPE FOR EXAMPLE, WHAT
TRANSFORMATION HAS HAPPENED
SINCE THESE PEOPLE AROSE.
EUROPE IS A TINY PART OF THE
WORLD.
ONE COULD STUDY THE AMERICAS,
ONE CAN STUDY EAST ASIA, ONE CAN
STUDY SOUTH ASIA, ONE CAN STUDY
AFRICA, MANY PARTS OF AFRICA,
AND THERE'S ALL OF THESE PLACES
TO STUDY AND I DID NOT MENTION
ANY PLACES.
THERE'S ALSO THINGS THAT ONE CAN
DEADO WITH ANCIENT DNA WHICH
WILL
ANSWER QUESTIONS THAT HAVE NOT
BEEN ANSWERED.
WE CAN PROBABLY USE DNA TO
ESTIMATE THE CENSUS SIZE OF
POPULATION.
YOU CAN SEE GENETICALLY IN
PEOPLE TODAY THAT -- CHINESE
HAVE A VERY LARGE DENS SIZE
BECAUSE THEY HAVE RELATIVE FEW
CHILDREN SO IF WE CAN GET
SUBSTANTIAL -- WE CAN ESTIMATE
POPULATION SIZE, SOMETHING WE'VE
NEVER DONE, AND THAT'S SO
IMPORTANT FOR ECONOMICS, FOR
HEALTH EVEN.
ANOTHER THAT'S VERY INTERESTING
IS THAT THIS BIG ARRIVAL OF
PEOPLE FROM THE STEPPE, HERDING
SHEEP, COME INTO EUROPE WHERE
THEY WERE DENSELY POPULATED BY
FARMER, HOW DO THEY MAKE AN
IMPACT WHERE PEOPLE THAT ALREADY
HAVE AN EFFICIENT WAY OF LIVING
CAN HAVE AN IMPACT.
THERE WAS A STUDY THAT STUD STUD
HE'D THE GENOME SEQUENCES OF
THESE SAMPLES AT THE TIME OF THE
IMPANGT, AND THEY FOUND OUT FROM
THESE FOUR TO 5,000 -- THERE IS
PLAGUE BACILLUS, WHICH SOME HAD
THOUGHT ONLY JUMPED INTO THE
SEVENTH CENTURY, BUT HERE IT IS
5,000 YEARS, IT DOESN'T HAVE THE
VIRULENCE FACTORS NEEDED FOR
BUBONIC PLAGUE BUT IT DOES FOR
PNEUMONIC PLAGUE.
5 TO 10% OF THE SAMPLES THAT
THEY STUDIED HAD PLAGUE IN THEIR
TEETH AT THE TIME THEY DIED,
WHICH MEANS THEY PROBABLY DIED
ON IT, AND ONE POSSIBILITY THAT
THESE PEOPLE SUGGESTED WHICH IS
AN EXCITING POSSIBILITY BUT
WHICH SHOWS THE POTENTIAL POWER,
EUROPE 5,000 YEARS AGO WERE LIKE
MAYTIVE AMERICANS, GENETICALLY
NAIVE POPULATION SUDDENLY
EXPOSED TO DISEASE WITH THE STEP
E AND THERE'S GREAT DISEASES
THAT SWEPT ACROSS EUROPE AT THIS
TIME AND MADE IT POSSIBLE FOR
PEOPLE TO WHO HAVE IN WHO
OTHERWISE WOULD NOT HAVE HAD THE
DEMOCRATIC NICHE.
>> I THINK HE'S RIGHT, THERE'S A
LOT OF WORK TO DO HERE.
IF YOU WANT TO CONTINUE THIS
CONVERSATION WITH DAVID, PLEASE
JOIN FOURS COFFE FOR COFFEE AND
COOKIES AN
D
MEANWHILE LET'S THANK OUR
SPEAKER AGAIN.
