UCLA-led team finds persistent effects of Neanderthal DNA in modern humans

Recent scientific discoveries have shown that Neanderthal genes comprise 1 to 4% of the genome of modern non-Africans, but the question has remained open as to how much those genes they are still actively influencing human traits so far.

A multi-institutional research team led by Sriram Sankararaman, associate professor of computer science, human genetics and computational medicine at UCLA, has developed a new suite of computational genetic tools to address the genetic effects of interbreeding between non-African humans and humans of Neanderthals which took place some 50,000 years ago.

In a study published in eLife, researchers have found that certain Neanderthal genes are responsible for certain traits in modern humans, including many with a significant influence on the immune system. Overall, however, the study shows that modern human genes are trumping succeeding generations.

For scientists studying human evolution interested in understanding how interbreeding with archaic humans tens of thousands of years ago still shapes the biology of many humans today, this study may fill in some of those gaps, said Sankararaman . More broadly, our findings may also provide new insights to evolutionary biologists who observe how echoes from these types of events can have both beneficial and harmful consequences.

Using a large UK Biobank dataset consisting of genetic and trait information from nearly 300,000 non-African Britons, the researchers analyzed more than 235,000 genetic variants that likely originated with Neanderthals. They found that 4,303 of these DNA differences play a substantial role in modern humans and affect 47 distinct genetic traits, such as the rate at which someone can burn calories or a person’s natural immune resistance to certain diseases.

For scientists studying human evolution interested in understanding how interbreeding with archaic humans tens of thousands of years ago still shapes the biology of many humans today, this study may fill in some of those gaps, Sriram said. Sankararaman.

Unlike previous studies which could not completely exclude genes from modern human variants, the new study took advantage of more precise statistical methods to focus on variants attributable to Neanderthal genes.

Interestingly, we found that many of the identified genes involved in modern human immune, metabolic and developmental systems may have influenced human evolution after ancestors migrated from Africa, said study lead author April (Xinzhu). Wei, an assistant professor of computer biology at Cornell University in New York. We have made our custom software available for free download and use by anyone interested in further research.

Although the study used a dataset of almost exclusively white individuals living in the UK, the new computational methods developed by the team could offer a path forward for gleaning evolutionary insights from other large databases to gain insight into the genetic influences of archaic humans on modern humans.

The study’s other co-lead author is Christopher Robles, a former UCLA genetics and genomics doctoral student recommended by Sankararaman.

Other authors are Sankararamans PhD student Ali Pazokitoroudi, Andrea Ganna of Massachusetts General Hospital and the Broad Institute of MIT and Harvard, Alexander Gusev and Arun Durvasula of Harvard Medical School, Steven Gazal of USC, Po-Ru Loh of the Broad Institute of MIT and Harvard and David Reich of Harvard University.

The research was supported by grants from the National Institutes of Health and the National Science Foundation, with additional funding from an Alfred P Sloan Research Fellowship and a gift from the Okawa Foundation. Other authors have received funding from the Paul G. Allen Frontiers Group, the John Templeton Foundation, the Howard Hughes Medical Institute, the Burroughs Wellcome Fund, and the Next Generation Fund at the Broad Institute of MIT and Harvard.

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