Long stretches of Neanderthal and Denisovan DNA helped Homo sapiens adapt, Ars Technica

        

University of Washington geneticist PingHsun Hsieh and his colleagues found Neanderthal and Denisovan versions of some genes in the genomes of people from Melanesia. These versions have several thousand base pairs of DNA that have been duplicated or deleted in the normal human versions. Most of this altered DNA is in or near genes related to metabolism, development, the life cycle of cells, communication among cells, or the immune system.

Those gene variants are surprisingly common among Melanesian peoples, and that could mean that their effects were useful enough that natural selection favored passing them along.

DNA from the Denisovans

AsHomo sapiensfirst ventured beyond Africa, they encountered other hominins already living in Europe and Asia, and those encounters left their mark on our modern genomes. Most people from outside Africa carry a little Neanderthal DNA (it makes up about one to four percent of the average non-African genome), and some people from East Asian, Melanesian, and indigenous Australian populations also have a bit of DNA inherited from Denisovans (about one to five percent of the average genome; it’s highest in Melanesian and indigenous and Australian people). Some of that DNA probably stuck with us for tens of thousands of years because it somehow helped our species adapt to new environments and challenges.

How does this DNA differ from the version found in modern humans? Thanks to the Neanderthal and Denisovan genomes recovered from ancient bones and teeth, scientists can recognize certain alleles that belong to our extinct cousins. Usually, when scientists talk about Neanderthal or Denisovan genes, they’re talking about alleles with small differences from theHomo sapiensversion — sometimes just a single nucleotide (one “letter” in the genetic code).

Sometimes those small changes don’t make a difference, but other times they’re enough to code for a different protein or cause a gene to be active under different conditions.

Hsieh and his colleagues looked for larger differences, in which tens of thousands of base pairs had either disappeared from the chromosome or had been repeated more times than usual. Geneticists call such changescopy-number variations, and they can be bad news; too many or too few copies of most genes can cause health problems or increase the risk of cancer. But some of the copy-number variations that Melanesian peoples inherited from Neanderthals and Denisovans actually seem to have been helpful.

DNA: The gift that keeps on giving

Hsieh and his colleagues studied genomes from modern people, looking for copy-number variants that showed up in the genomes of Neanderthals or Denisovans. They focused on those that appeared in modern people from outside Africa but not in modern people from Africa, whose ancestors wouldn’t have run into Neanderthals or Denisovans. They found a total of 51 such chunks of genetic code.

Hsieh and his colleagues were especially curious about Melanesia because the average Melanesian person has a higher percentage of Denisovan DNA in their genome (between three and five percent) than the average member of any other group of people. In a sample of Melanesian people’s genomes from research databases, they found 37 copy-number variations that showed up in a larger portion of the population than you’d expect just by random genetic chance.

In other words, it looked like natural selection had acted in favor of those 37 pieces of DNA, making them more common because they somehow helped people live and reproduce more successfully.

Of those 37 apparently helpful sets of duplicated DNA, 19 appeared to have originally come from the Neanderthal or Denisovan genomes. “It is tempting to hypothesize that [DNA] introgression from other hominins may have played a key role in helping humans [who were] migrating out of Africa adapt to new environments by serving as a reservoir of beneficial alleles,” wrote Hsieh and his colleagues .

But there’s still a large gap between seeing that a genetic variant is likely to have been helpful enough for natural selection to kick in and being able to say exactly what that variantdoes. It is, however, possible to make some general predictions based on which genes are nearby. Based on that, it looks like most of the copy-number variants affect genes — associated with things like metabolism, the immune system, and embryonic development. So far, however, Hsieh and his colleagues can’t be sure of the details.

The complex history of chromosome 16

One of the largest and most complex sequences in the study appears to be somehow associated with iron regulation during the development of an embryo. The 383 – base-pair sequence (which contains two copied sections of DNA) happens to be located near a spot on chromosome 16 that’s already prone to rearrangements. Those rearrangements are associated with the second most common genetic cause of autism that we know of, which affects about one percent of diagnosed people.

Based on what we know about how quickly DNA changes over time, Hsieh and his colleagues say that between 500, 00 0 and 2.5 million years ago, a complex series of changes happened on chromosome 16 in the Denisovans. Some genes got copied, others got deleted, and still others just got rearranged. Eventually, about 60, 00 0 to 170, 00 0 years ago, the resulting alleles got passed toHomo sapiens, likely somewhere between southeast Asia and Melanesia. Today, the Denisovan variant shows up in about 80 percent of people in the lowlands of New Guinea.

That section of chromosome 16 already had its own copy-number variant in humans, which originated around 280, 00 0 years ago. As a result of the extra DNA, that area of ​​the genome was already vulnerable to having its code rearranged. Hsieh and his colleagues suggest that the altered DNA could influence how often the genetic code gets rearranged. But that benefit could also impact the frequency of autism among Melanesians, although it’s much, much too early to draw firm conclusions.

What is increasingly clear, however, is that many modern people still carry aspects of our extinct hominin relatives with us. The next step is to unravel exactly how those surviving bits of ancient DNA may still influence the lives and health of modern populations.

Science, 2019. DOI:10 . 1126 / science .aax 2083 (About DOIs).