An international research team led by Martin Petr and Janet Kelso from the Max Planck Institute for Evolutionary Anthropology in Leipzig has determined the Y chromosome sequences of three Neanderthals and two Denisovans. These Y chromosomes provide new insights into the kinship relationships and population histories of archaic and modern humans, including new evidence of ancient gene flow from very early modern humans to Neanderthals. The data show that these interactions may have been of benefit to the Neanderthals, as the gene flow resulted in a complete exchange of the Neanderthals' Y chromosomes.
In 1997 the very first Neanderthal DNA sequence—only a small part of the mitochondrial genome—was obtained from an individual found in a cave in the Neanderthal in 1856. Since then, improvements in molecular methods have made it possible for researchers at the Max Planck Institute for Evolutionary Anthropology to sequence the entire autosomal genomes of several Neanderthals in high quality and led to the discovery of the Denisovans, a previously completely unknown extinct human form.
However, since all the remains of Neanderthals and Denisovans from which larger amounts of DNA could be isolated came from female individuals, extensive studies of their Y chromosomes have not been possible so far. In contrast to all other parts of the autosomal genome, which is a mosaic of thousands of family trees of the ancestors of every single individual, Y chromosomes have a special type of inheritance: they are passed on exclusively from father to son. Y chromosomes—as well as the mitochondrial DNA inherited exclusively from the mother's side—are therefore so valuable for research into human history.
New method
For their study, the scientists identified three male Neanderthals and two Denisovans who were suitable for DNA analysis and developed a method by which they extracted fragments of human Y chromosomes from the large amount of microbial DNA fragments, which are typically old bones and teeth could contaminate, fish out. This enabled them to reconstruct the Y chromosome sequences of these individuals, which would not have been possible using previous methods. By comparing the archaic human Y chromosomes with each other and with the Y chromosomes of people living today, the researchers found that Y chromosomes from Neanderthals are more similar to those of modern humans than those of Denisovans.
"That was quite a surprise to us. We know from studies of their autosomal DNA that Neanderthals and Denisovans are closely related, and that humans living today are their more distant evolutionary cousins. We had expected that the Y chromosomes would show a similar picture, ”says Martin Petr, the study's lead author.
The scientists also calculated that the last common ancestor of the Y chromosomes lived in Neanderthals and modern humans around 370,000 years ago must have, so much later than previously assumed.
It is now widely accepted that all non-African descent have a small amount of Neanderthal DNA in them. This is the result of an intermingling of Neanderthals and modern humans that occurred about 50,000 to 70,000 years ago, shortly after modern humans moved out of Africa and began to spread around the world. However, whether the Neanderthals also had modern human DNA has been a matter of dispute.
Early mixing
The now available sequences of the Y chromosomes provide further evidence that Neanderthals and early modern humans may have met and mixed with each other 370,000 years ago, or at the latest more than 100,000 years ago. This means that a population closely related to early modern humans must have reached Eurasia by that time. Surprisingly, this intermingling resulted in the replacement of the original Y chromosomes of Neanderthals with those of early modern humans. A similar pattern was shown in a previous study for the mitochondrial DNA of Neanderthals.
At first, the complete replacement of both the Y chromosomes and the mitochondrial DNA of the early Neanderthals was a mystery to scientists, as it is unlikely that such events could be ascribed to chance alone. However, the researchers used computer simulations to show that the small size of the Neanderthal populations may have led to an accumulation of harmful mutations in their Y chromosomes and decreased evolutionary fitness. This is similar to scenarios where extremely small population sizes and inbreeding increase the incidence of certain diseases. "Given the important role of the Y chromosome in fertility and reproduction, we suspect that the lower evolutionary fitness of the Y chromosomes in Neanderthals led to natural selection.
Janet Kelso, the study's lead author, is optimistic that this exchange hypothesis can be tested in the near future: "If we can obtain Y chromosome sequences from Neanderthals who lived before this hypothetical early exchange event, such as the 430,000-year-old Neanderthals from the Sima de los Huesos cave in Spain, according to our prediction, they will still have the original Neanderthal Y-chromosomes and will therefore be more similar to the Denisovans than to modern humans," she said.
Republished courtesy of Max Planck Gesellschaft. Photo: Matthias Meyer in the clean room at the Max Planck Institute for Evolutionary Anthropology. Credit: © MPI Evolutionary Anthropology