Persistent effects of Neanderthal DNA found in modern humans

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Benchmarking approaches to estimate heritability components of Neanderthal introgression. We group the simulations based on the relationships between minor allele frequency (MAF) and SNP-local linkage disequilibrium on effect size (MAF-LD coupling): BASELINE, COMMON, RARE, HIGH, LOW. In each group, we performed 12 simulations with varying polygenicity and heritability (see Methods). Furthermore, we combine the results of all simulations together as ALL. Credit: and Life (2023). DOI: 10.7554/eLife.80757

Recent scientific discoveries have shown that Neanderthal genes comprise 1 to 4% of the genome of today’s humans whose ancestors migrated from Africa, but the question has remained open as to how actively those genes are still influencing human traits. until now.

A multi-institutional research team, including Cornell, has developed a new suite of computational genetic tools to address the genetic effects of interbreeding between humans of non-African ancestry and Neanderthals about 50,000 years ago. (The study only applies to descendants of those who migrated from Africa before Neanderthals went extinct, and particularly those of European ancestry.)

In a study published in and Life, researchers have reported 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.

“Interestingly, we found that many of the identified genes involved in modern human immune, metabolic and developmental systems may have influenced human evolution after ancestral migration out of Africa,” said study co-author April (Xinzhu) Wei, an assistant professor of computational biology in the College of Arts and Sciences. “We’ve made our custom software available for free download and use by anyone interested in further research.”

Using a large UK Biobank dataset consisting of genetic and trait information from nearly 300,000 Britons of non-African ancestry, 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 influence 47 distinct genetic traits, such as how quickly someone can burn calories or a person’s natural immune resistance to certain diseases.

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.

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.

“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,” he said. senior research scientist Sriram Sankararaman, an associate professor at the University of California, Los Angeles. ‘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.’

More information:
Xinzhu Wei et al, The lingering effects of Neanderthal introgression on human complex traits, and Life (2023). DOI: 10.7554/eLife.80757

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