Wednesday, January 29, 2014

The Little Bit of Neanderthal in All of Us. By Carl Zimmer.

A reconstruction of a Neanderthal skeleton, right, with a modern human skeleton in the background. Frank Franklin II/Associated Press.

The Little Bit of Neanderthal in All of Us. By Carl Zimmer. New York Times, January 29, 2014.

Toe Fossil Provides Complete Neanderthal Genome. By Carl Zimmer. NJBR, December 20, 2013. With related articles.

The genomic landscape of Neanderthal ancestry in present-day humans. By Siriram Sankararaman et al. Nature, published online January 29, 2014.


Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture. The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci. We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans. Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

The Date of Interbreeding between Neandertals and Modern Humans. By Siriram Sankararaman et al. PLOS Genetics, October 4, 2012. Also here.


Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000–86,000 years before the present (BP), and most likely 47,000–65,000 years ago. This supports the recent interbreeding hypothesis and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa.

Resurrecting Surviving Neandertal Lineages from Modern Human Genomes. By Benjamin Vernot and Joshua M. Akey. Science, published online January 29, 2014.


Anatomically modern humans overlapped and mated with Neandertals such that non-African humans inherit ~1-3% of their genomes from Neandertal ancestors. We identified Neandertal lineages that persist in the DNA of modern humans, in whole-genome sequences from 379 European and 286 East Asian individuals, recovering over 15 Gb of introgressed sequence that spans ~20% of the Neandertal genome (FDR = 5%). Analyses of surviving archaic lineages suggests that there were fitness costs to hybridization, admixture occurred both before and subsequent to divergence of non-African modern humans, and Neandertals were a source of adaptive variation for loci involved in skin phenotypes. Our results provide a new avenue for paleogenomics studies, allowing substantial amounts of population-level DNA sequence information to be obtained from extinct groups even in the absence of fossilized remains.


Ever since the discovery in 2010 that Neanderthals interbred with the ancestors of living humans, scientists have been trying to determine how their DNA affects people today. Now two new studies have traced the history of Neanderthal DNA, and have pinpointed a number of genes that may have medical importance today.
Among the findings, the studies have found clues to the evolution of skin and fertility, as well as susceptibility to diseases like diabetes. More broadly, they show how the legacy of Neanderthals has endured 30,000 years after their extinction.
“It’s something that everyone wanted to know,” said Laurent Excoffier, a geneticist at the University of Bern in Switzerland who was not involved in the research.
Neanderthals, who became extinct about 30,000 years ago, were among the closest relatives of modern humans. They shared a common ancestor with us that lived about 600,000 years ago.
In the 1990s, researchers began finding fragments of Neanderthal DNA in fossils. By 2010 they had reconstructed most of the Neanderthal genome. When they compared it with the genomes of five living humans, they found similarities to small portions of the DNA in the Europeans and Asians.
The researchers concluded that Neanderthals and modern humans must have interbred. Modern humans evolved in Africa and then expanded out into Asia and Europe, where Neanderthals lived. In a 2012 study, the researchers estimated that this interbreeding took place between 37,000 and 85,000 years ago.
Sir Paul A. Mellars, an archaeologist at the University of Cambridge and the University of Edinburgh, who was not involved in the research, said the archaeological evidence suggested the opportunity for modern humans to mate with Neanderthals would have been common once they expanded out of Africa. “They’d be bumping into Neanderthals at every street corner,” he joked.
The first draft of the Neanderthal genome was too rough to allow scientists to draw further conclusions. But recently, researchers sequenced a far more accurate genome from a Neanderthal toe bone.
Scientists at Harvard Medical School and the Max Planck Institute for Evolutionary Anthropology in Germany compared this high-quality Neanderthal genome to the genomes of 1,004 living people. They were able to identify specific segments of Neanderthal DNA from each person’s genome.
“It’s a personal map of Neanderthal ancestry,” said David Reich of Harvard Medical School, who led the research team. He and his colleagues published their results in the journal Nature.
Living humans do not have a lot of Neanderthal DNA, Dr. Reich and his colleagues found, but some Neanderthal genes have become very common. That’s because, with natural selection, useful genes survive as species evolve. “What this proves is that these genes were helpful for non-Africans in adapting to the environment,” Dr. Reich said.
In a separate study published in Science, Benjamin Vernot and Joshua M. Akey of the University of Washington came to a similar conclusion, using a different method.
Mr. Vernot and Dr. Akey looked for unusual mutations in the genomes of 379 Europeans and 286 Asians. The segments of DNA that contained these mutations turned out to be from Neanderthals.
Both studies suggest that Neanderthal genes involved in skin and hair were favored by natural selection in humans. Today, they are very common in living non-Africans.
The fact that two independent studies pinpointed these genes lends support to their importance, said Sriram Sankararaman of Harvard Medical School, a co-author on the Nature paper. “The two methods seem to be converging on the same results.”
It is possible, Dr. Akey speculated, that the genes developed to help Neanderthal skin adapt to the cold climate of Europe and Asia.
But Dr. Akey pointed out that skin performs other important jobs, like shielding us from pathogens. “We don’t understand enough about the biology of those particular genes yet,” he said. “It makes it hard to pinpoint a reason why they’re beneficial.”
Both teams of scientists also found long stretches of the living human genomes where Neanderthal DNA was glaringly absent. This pattern could be produced if modern humans with certain Neanderthal genes could not have as many children on average as people without them. For example, living humans have very few genes from Neanderthals involved in making sperm. That suggests that male human-Neanderthal hybrids might have had lower fertility or were even sterile.
Overall, said Dr. Reich, “most of the Neanderthal genetic material was more bad than good.”
Some of the Neanderthal genes that have endured until today may be influencing people’s health. Dr. Reich and his colleagues identified nine Neanderthal genes in living humans that are known to raise or reduce the risk of various diseases, including diabetes and lupus.
To better understand the legacy of Neanderthals, Dr. Reich and his colleagues are collaborating with the UK Biobank, which collects genetic information from hundreds of thousands of volunteers. The scientists will search for Neanderthal genetic markers, and investigate whether Neanderthal genes cause any noticeable differences in anything from weight to blood pressure to scores on memory tests.
“This experiment of nature has been done,” said Dr. Reich, “and we can study it.”