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When populations collide
by Staff Writers
Los Angeles CA (SPX) Feb 03, 2014

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More than thirty thousand years ago, Homo sapiens migrating out of Africa began encountering Neanderthals, a lineage that had diverged from modern humans hundreds of thousands of years before. Despite their differences, Homo sapiens and Neanderthals mingled, and over time, produced children with genes from both lineages. Today, the biological remnants of that collision between two distinct populations remain alive in the genomes of humans with European and Asian ancestry.

Now, Howard Hughes Medical Institute (HHMI) researchers at Harvard Medical School have analyzed exactly which areas of the human genome retain segments of Neanderthal DNA, passed down throughout the generations. The findings were published January 29, 2014 in Nature.

"The goal was to understand the biological impact of the gene flow between Neanderthals and modern humans," says David Reich, an HHMI investigator at Harvard Medical School and the lead scientist on the new research. "We reasoned that when these two groups met and mixed, some new traits would have been selected for and remained in the human genome, while some incompatibilities would have been selected against and removed."

Reich has been interested in what happens when populations collide. "Throughout history, groups of humans have been on the move. Until recently, researchers did not have the ability to learn much about what happened when two populations met each other, and in particular whether they mixed or one replaced the other," Reich says. What really happens, he argues, is that populations mix, and that later people carry DNA from both ancestral groups.

In late 2013, Reich was one of the leaders of a team that published the complete genome of a Neanderthal woman, based on analysis of DNA isolated from a toe bone discovered in modern-day Siberia. To determine how the human-Neanderthal genetic mixing may have played out, Reich and his colleagues compared that completed Neanderthal genome with the genomes of 1,004 present-day humans from around the globe.

"If a gene variant is absent in Africans today, but present in modern day non-Africans as well as the Neanderthal genome, that's good evidence that it originates from Neanderthals," Reich says. Since humans met Neanderthals as they migrated out of Africa, those populations that remained in Africa had little contact or genetic mixing with Neanderthals. Reich's group also leveraged other genetic information, including the size of different gene fragments, to determine whether genes were inherited from Neanderthals or not.

The researchers found that today, humans in east Asia have, on average, more of their genome originating from Neanderthals than Europeans, and modern-day Africans have little or none. Those findings confirmed previous studies. But then, the scientists took their analysis a step further and examined which genes most often have Neanderthal ancestry in present-day people. They found that some genes had variants of Neanderthal origin in more than sixty percent of Europeans or Asians, while other genes were never of Neanderthal heritage.

The scientists discovered that the genetic changes most often inherited from Neanderthals were disproportionately in genes related to keratin, a component of skin and hair.

"This suggests that as humans were adapting to the non-African environment they were moving into, they may have been able to exploit adaptations that Neanderthals had already achieved," Reich says. More work is needed, however, to show the exact biological implications of the Neanderthal keratin genes and how they differ from the versions of keratin related proteins that would have already been present in modern humans.

His group analyzed not only which Neanderthal genes remain in the human population today, but also which parts of today's genomes lack Neanderthal genes altogether.

"The most interesting findings were about the places in the genome that are devoid of Neanderthal genes - 'Neanderthal ancestry deserts'," says Reich. "At these locations, Neanderthal genetic material was not tolerated by modern humans and removed by the action of natural selection."

The most striking area of the human genome that lacked Neanderthal genes was the X chromosome-one of the sex chromosomes. In humans, women have two X chromosomes and men have an X and a Y chromosome. The team's observation that the X chromosome had very little Neanderthal ancestry suggested something the scientists hadn't predicted -- a biological phenomenon called hybrid sterility. When two organisms are distantly related, Reich explains, genes related to fertility, inherited on the X chromosome, can interact poorly with genes elsewhere in the genome. The interference between the pairs of genes can render males-who only have one X chromosome-infertile.

"When you have populations that have sufficiently diverged, this male-only sterility can occur," Reich says.

To confirm whether hybrid sterility could have occurred during the interbreeding between modern humans and Neanderthals, Reich's team looked at whether genes expressed in the testes were more or less enriched in Neanderthal DNA. Indeed, genes important for the functioning of the testes had a particularly low inheritance of Neanderthal ancestry. The combined evidence that both the testes and the X chromosome lack Neanderthal DNA, Reich says, suggests that modern human males who inherited a Neanderthal X chromosome often may have been unable to have children, and therefore pass along this X chromosome. Today, that translates into a near- absence of Neanderthal DNA on the X chromosomes of humans.

"It tells us that when Neanderthals and modern humans met and mixed, they were at the very edge of being biological compatible," he says.

Further studies on the legacy of Neanderthal genes in human biology could help shed light on not only human history, but the overall biological idea of hybrid sterility.

"The other direction we want to go is to use this information as a tool for understanding human disease genes," Reich adds. Already, the new study revealed that genetic changes that affect risk for lupus, diabetes, and Crohn's Disease likely originate from Neanderthals.


Related Links
Howard Hughes Medical Institute
All About Human Beings and How We Got To Be Here

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Neanderthal lineages excavated from modern human genomes
Seattle WA (SPX) Feb 03, 2014
A substantial fraction of the Neanderthal genome persists in modern human populations. A new approach applied to analyzing whole-genome sequencing data from 665 people from Europe and East Asia shows that more than 20 percent of the Neanderthal genome survives in the DNA of this contemporary group, whose genetic information is part of the 1,000 Genomes Project. Previous research proposes t ... read more

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