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Neanderthals, denisovans, and prehistoric family inbreeding

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Neanderthals interbred with their family members, say archaeogenetics researchers from the University of California - Berkeley. A team that includes UC Berkeley population geneticists has produced the first high-quality genome of a Neanderthal, allowing comparison with the genomes of modern humans and Denisovans. Neanderthals and Denisovans genetically split from one another about 300,000 years ago.

The analysis shows a long history of interbreeding among these early humans and a fourth, previously unknown group. The Neanderthal, from Denisova cave, also shows evidence of inbreeding. About 87 genes in modern humans were found to be significantly different from related genes in Neanderthals and Denisovans.

Neanderthal genome shows early human interbreeding, inbreeding, says a new study. First high-quality genome sequence allows comparison with human, Denisovan DNA, says a December 18, 2013 news release, "Neanderthal genome shows early human interbreeding, inbreeding." The most complete sequence to date of the Neanderthal genome, using DNA extracted from a woman's toe bone that dates back 50,000 years, reveals a long history of interbreeding among at least four different types of early humans living in Europe and Asia at that time, according to University of California - Berkeley, scientists.

Population geneticist Montgomery Slatkin, graduate student Fernando Racimo and post-doctoral student Flora Jay were part of an international team of anthropologists and geneticists who generated a high-quality sequence of the Neanderthal genome and compared it with the genomes of modern humans and a recently recognized group of early humans called Denisovans.

The comparison shows that Neanderthals and Denisovans are very closely related, and that their common ancestor split off from the ancestors of modern humans about 400,000 years ago

Though Denisovans and Neanderthals eventually died out, they left behind bits of their genetic heritage because they occasionally interbred with modern humans. The research team estimates that between 1.5 and 2.1 percent of the genomes of modern non-Africans can be traced to Neantherthals.

Denisovans also left genetic traces in modern humans, though only in some Oceanic and Asian populations. The genomes of Australian aborigines, New Guineans and some Pacific Islanders are about 6 percent Denisovan genes, according to earlier studies. The new analysis finds that the genomes of Han Chinese and other mainland Asian populations, as well as of native Americans, contain about 0.2 percent Denisovan genes.

The genome comparisons also show that Denisovans interbred with a mysterious fourth group of early humans also living in Eurasia at the time. That group had split from the others more than a million years ago, and may have been the group of human ancestors known as Homo erectus, which fossils show was living in Europe and Asia a million or more years ago.

"The paper really shows that the history of humans and hominins during this period was very complicated," explains Slatkin, in a December 18, 2013 news release, "Neanderthal genome shows early human interbreeding, inbreeding." Slatkin is a UC Berkeley professor of integrative biology. "There was lot of interbreeding that we know about and probably other interbreeding we haven't yet discovered." Slatkin, Racimo and Jay are members of a large team led by former UC Berkeley post-doc Svante Pääbo, who is now at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

You can check out online in the journal Nature the abstract of the latest research on prehistoric interbreeding published December 18, 2013 in the journal Nature, "The complete genome sequence of a Neanderthal from the Altai Mountains," or see the abstract of other research published on December 4, 2013, "A mitochondrial genome sequence of a hominin from Sima de los Huesos."

The genome analysis will be published in the Dec. 19, 2013 issue of the journal Nature

In another analysis, Jay discovered that the Neanderthal woman whose toe bone provided the DNA was highly inbred. The woman's genome indicates that she was the daughter of a very closely related mother and father who either were half-siblings who shared the same mother, an uncle and niece or aunt and nephew, a grandparent and grandchild, or double first-cousins (the offspring of two siblings who married siblings).

Further analyses suggest that the population sizes of Neanderthals and Denisovans were small and that inbreeding may have been more common in Neanderthal groups than in modern populations. The scientists studied the genes that pointed to inbreeding within that family group.

Neanderthal woman's genome shows she was highly inbred

As part of the new study, Racimo was able to identify at least 87 specific genes in modern humans that are significantly different from related genes in Neanderthals and Denisovans, and that may hold clues to the behavioral differences distinguishing us from early human populations that died out.

"There is no gene we can point to and say, 'This accounts for language or some other unique feature of modern humans,'" Slatkin says in the news release. "But from this list of genes, we will learn something about the changes that occurred on the human lineage, though those changes will probably be very subtle."

A catalog of genetic features is revealed

According to Pääbo, the list of genes "is a catalog of genetic features that sets all modern humans apart from all other organisms, living or extinct. I believe that in it hide some of the things that made the enormous expansion of human populations and human culture and technology in the last 100,000 years possible".

The Pääbo group last year produced a high-quality Denisovan genome based on DNA from a pinky finger bone discovered in 2008 in Denisova Cave in the Altai Mountains of Southern Siberia. That bone is from a young woman who lived about 40,000 years ago.

The Neanderthal toe bone was found in the same cave in 2010, though in a deeper layer of sediment that is thought to be about 10,000-20,000 years older. The cave also contains modern human artifacts, meaning that at least three groups of early humans occupied the cave at different times. The Pääbo group developed new techniques to extract DNA from these old bones.

Neanderthals and modern humans co-existed in Europe and Asia for at least 30,000 years

Slatkin noted that no one is sure how long the various now-extinct groups lasted, but that there is evidence that Neanderthals and modern humans coexisted in Europe and Asia for at least 30,000 years. Interbreeding was infrequent, though how infrequent is unclear given the genomic information available today.

"We don't know whether interbreeding took place once, where a group of Neanderthals got mixed in with modern humans, and it didn't happen again, or whether groups lived side by side, and there was interbreeding over a prolonged period," he says, according to the news release.

Researchers find that the sunlight adaptation region of Neanderthal genome also is found in up to 65 percent of modern East Asian population

Recent highlights are now published December 13, 2013 in the journal Molecular Biology and Evolution (Oxford University Press. You can check out the abstract of the new research, "Neanderthal Introgression at Chromosome 3p21.31 was Under Positive Natural Selection in East Asians."

With the Neanderthal genome now published, for the first time, scientists have a rich new resource of comparative evolution. For example, recently, scientists have shown that humans and Neanderthals once interbreed, with the accumulation of elements of Neanderthal DNA found in up to 5 percent in modern humans.

Are there any advantages to the retention of Neanderthal DNA that favors modern humans?

In a new article published December 13, 2013 in the journal Molecular Biology and Evolution, authors Jin, et. al., present evidence for the accumulation of a Neanderthal DNA region found on chromosome 3 that contains 18 genes, with several related to UV-light adaptation, including the Hyal2 gene. Their results reveal this region was positively selected and enriched in East Asians, ranging from up to 49 percent in Japanese to 66 percent in Southern Chinese.

Interestingly, the authors note, the geographic distribution of the Neanderthal genomic region suggests that UV-light mutations were shown to be lost during the exodus of modern human from Africa, and reintroduced to Eurasians from Neanderthals. The topic is still controversial in scientific discussions, according to the December 17, 2013 news release, "Sunlight adaptation region of Neanderthal genome found in up to 65 percent of modern East Asian population."

Are there higher levels of Neanderthal ancestry in East Asians than in Europeans?

"Overall, it is still very controversial whether there is more Neanderthal DNA contributions to Asians than Europeans, as we have evidence to argue against this," says Lin, according to the December 17, 2013 news release, Sunlight adaptation region of Neanderthal genome found in up to 65 percent of modern East Asian population. "Although in the case of the Hyal2 variant, it did indeed have a higher frequency in Asians."

From 45,000 years to 5,000 years before present, effective population sizes of the Neanderthal region (the geographic area that Neanderthals previously occupied) increased at a steady rate. Notably, the growth rate of the effective population size increased at around 5,000 to 3,500 years before present, which suggests a population expansion event. This Asian-specific Neanderthal evolutionary event is also consistent with previous reports of higher levels of Neanderthal ancestry in East Asians than in Europeans.

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