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PORTSIDE  July 2011, Week 4

PORTSIDE July 2011, Week 4

Subject:

Human History Writ Large in a Single Genome

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Date:

Fri, 22 Jul 2011 21:41:26 -0400

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Human History Writ Large in a Single Genome

     The first humans to leave Africa continued to
     interbreed with Africans for tens of thousands of
     years.

Ewen Callaway
Nature
Published online 13 July 2011
http://www.nature.com/news/2011/110713/full/news.2011.413.html
doi:10.1038/news.2011.413

Stored inside Craig Venter's genome are clues to the
history of humankind, including global migrations and
population crashes. Researchers have mined the genomics
pioneer's publicly available DNA sequence, and those of
6 others, to reveal major milestones in human history.

"You can take a single person's genome and learn an
entire population's history from it," says David Reich,
a geneticist at Harvard Medical School in Boston,
Massachusetts, who was not involved in the study. "This
is one of the dreams we've had as a community."

The analysis, published today in Nature[1], suggests
that descendants of the first humans to leave Africa
dwindled to little more than 1,000 reproductively active
individuals before rebounding. The study also suggests
that, contrary to assumptions made from archaeological
evidence, these early humans continued to breed with
sub--Saharan Africans until as recently as 20,000 years
ago.

Maternal ties

Geneticists eager to plumb human history have
traditionally compared DNA sequences from numerous
people around the world to determine how different
populations relate to one another and when they might
have gone their separate ways. For instance, studies of
DNA from maternally inherited cell structures called
mitochondria established that all humans can trace their
maternal lineage back to one woman -- a mitochondrial
Eve -- who lived in Africa around 200,000 years ago[2].

But, just as mitochondria can lead us back to a single
woman, parts of a person's genome inherited from both
their mother and father can also be followed back in
time, with individual genes traced back to points before
any mutations had developed, when just one version -- a
common ancestor -- of that gene existed. Because of the
way a person's maternal and paternal chromosomes shuffle
together to create diversity in their sperm or egg
cells, some parts of a person's genome inevitably share
common ancestors more recently than other parts.

"Each little piece of the genome has its own unique bit
of history and goes to a unique ancestor as you go
further and further back," explains John Novembre, a
population geneticist at the University of California,
Los Angeles, who was not involved in the study. "As you
look at different parts of the genome, you get access to
different parts of history."

On the basis of this principle, Richard Durbin, a genome
scientist at the Wellcome Trust Sanger Institute near
Cambridge, UK, and his then post-doc Heng Li determined
a way to calculate, from the ages of different segments
of a single person's genome, changes in the population
size of their ancestors.

The genomes of Venter and two others of European
ancestry, two Asian men and two West African men all
tell the same story up until about 100,000 years ago,
when their populations began to split and then plummet
in size, probably reflecting the first human migrations
out of Africa.

The ancestors of Asians and Europeans dwindled by a
factor of ten to roughly 1,200 reproductively active
people between 20,000 and 40,000 years ago, Durbin and
Li calculate. African populations also crashed, but by
nowhere near the same extent, dropping to around 5,700
breeding individuals. Other studies have recorded
population crashes at around the same time, Reich says.

In a different analysis, Durbin and Li compared an X
chromosome from an African with one from a non-African
to determine when their ancestors stopped interbreeding
after the first humans left Africa and colonized other
parts of the world. Human remains and artefacts
unearthed in Europe, Asia and Australia seem to suggest
humans rapidly colonized these places by about 40,000
years ago, diminishing the opportunities to interbreed
with Africans.

However, Durbin and Li suggest that these groups
continued to interbreed until as recently as 20,000
years ago. One possible explanation, Durbin says, is
that after the first humans left Africa some 60,000
years ago, successive waves of Africans followed suit,
interbreeding with the ancestors of the earlier
migrants.

Mix and match

Chris Stringer, a palaeoanthropologist at the Natural
History Museum in London, says that human populations
outside Africa were probably small and widely dispersed
20,000-50,000 years ago, so regular interbreeding with
Africans seems unlikely. "There could have been surges
of gene flow at particular times, driven by innovations
or environmental change, but it would be surprising if
these continued right through that period," he says.

Mining individual genomes can't reveal every chapter of
human history, notes Reich, who now works with Li at the
Broad Institute of Harvard and MIT in Cambridge,
Massachusetts. The approach reveals little about
upheavals of the last 20,000 years, such as the peopling
of the Americas, because few chunks of the genome are
young enough. Similarly, Durbin and Li's method can't
deduce the history of human ancestors who existed before
about 2 million years ago because few regions of the
genome are much older.

Despite these limitations, Reich plans to lean heavily
on the new approach, not least for work on ancient
genomes belonging to Neanderthals[3] and a mysterious
sister population, known as Denisovans, discovered
through DNA recovered from a 30,000-50,000-year-old
finger bone found in a Siberian cave[4]. Reich and his
colleagues have been unable to determine when
Neanderthals and Denisovans stopped breeding with one
another, and the new approach has the potential to
answer that question.

References

[1] Li, H. & Durbin, R. Nature doi:10.1038/nature10231
(2011).

[2] Cann, R. L., Stoneking, M. & Wilson, A. C. Nature
325, 31--36 (1987).

[3] Green, R. E. et al. Science 328, 710--722 (2010).

[4] Krause, J. et al. Nature 464, 894--897 (2010).

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