Comprehensive DNA analysis of modern Melanesians shows that an assortment of mutated genes inherited from extinct Neanderthals and denisovans provided evolutionary advantages such as the ability to consume new foods and avoid infections, among other important benefits.

Neanderthals and denisovans became extinct between 35,000 and 40,000 years ago, but not before these closely related hominins intertwined with modern humans. To this day, the legacy of these interbreeding episodes live on in our DNAat measure among people of European and Asian descent. As for why some of these archaic genes are stuck around over aeons not fully understood, and their potential role in human functioning and health, whether good or bad.

A new study published today in the journal Science delves into these unknowns, revealing new evidence suggesting that some of these inherited genes among at least modern Melanesians have conferred certain evolutionary benefits, the exact nature of which has yet to be determined.

Our study shows that previously unknown large genomic structural changes that originated in our now extinct close relatives and were subsequently introgressed or introduced back into our genomeplay an important role in human evolution, explained PingHsun Hsieh, a geneticist in the Department of genomic Sciences at the University of Washington in Seattle and lead researcher of the new work, in an email to Gizmodo. We are also identifying new genes spanning these large genomic variants that could be useful for Melanesians and help them adapt to their local island environment.

By previously unknown major genomic structural changes, Hsieh is referring to copy number variants (CNVs), as opposed to simpler single nucleotide variants (SNVs). Simply put, CNVs are changes in large batches of genetic bases, or nucleotide letters (typically 50 or more), while SNVs describe a single underlying mutation in the genome. These types of mutations can occur either due to gain or loss of genomic material, and both can affect how some genes function.

For example, a particularly remarkable and tireless mutation of SNV has allowed some European populations to drink milk (i.e. the ability to produce lactase throughout adulthood). CNVs, due to their size and complexity, tend to have a negative impact on human health. Several CNVs on chromosome 16 have been associated with autism, for example. Other CNVs are known to contribute to psoriasis, schizophrenia, obesity, and Crohn’s disease. But CNVs isn’t all bad, with positive effects including the ability to metabolize steroids, resist certain diseases, and digest starch, among other things.

Whether SNV or CNV, these mutations are subject to natural selection processes. Over time, new traits stemming from these mutations will either be positively or negatively selected, so a fair assumption is that if a trait persists for a long time at all, its probably adaptive in some way. But since SNVs are much easier to study than CNVs, less is known about the role that CNVs play in hominin evolution and whether the influx of these mutated archaic genes due to interbreeding was somehow beneficial. A new study attempts to fill this important gap.

The most likely reason CNVs have not been addressed in previous studies of archaic introgression is that CNVs is difficult to genotype accurately, Sharon Browning, a research Professor in the Department of biostatistics at the University of Washington, writes in an email to gizmodo. Browning, who knows the team personally but was not involved in their new study, said the paper’s senior author, Evan Eichler, is a leading expert on CNVs, so his team has the experience to pull this off.

For the study, Hseih and Eichler, along with their colleagues, analyzed Melanesian genomes in the search for inheritedand potentially adaptiveCNVs. Modern Melanesians, who today inhabit the geographical region stretching from New Guinea out to Fiji, have retained a disproportionate amount of archaic DNA from both Neanderthals and Denisovans, making them ideal candidates for this research. As to why Melanesians have more archaic DNA than other human populations, thats not fully understood, but its likely because their ancestors had more contact with these now-extinct hominins.

Melanesians have a lot more archaic introgression than most other populations because they not only have the Neanderthal introgression that is shared with all out-of-Africa populations, but they also have a large amount of Denisovan introgression, whereas other populations have only a little (Asian populations) or none (European populations), said Browning. A hypothesis is that the ancestors of Melanesians met a population of Denisovans and [interbred] with them after they had started hopping across the islands to get to Melanesia, and there wasnt much back and forth with the Eurasian continental mainland after that event.

Indeed, the ancestors of modern Melanesians have been largely isolated for 50,000 years of their history, only mixing with populations from the West for the past 3,000 years.

For the analysis, the researchers applied a statistical method to identify large CNVs that originated from Neanderthals and denisovans and were introduced into the Melanesian population between 40,000 to 120,000 years ago. Genome sequencing technologies were then used to confirm these findings. Comparison and analysis of genomic data indicate a common origin rather than spontaneous mutations (a process known as convergent evolution).

Most CNVs are pernicious, but pernicious introgressed CNVs have generally been removed from the population of choice, so will not be found in this study, Browning said. Since CNVs are more complex than SNVs, it is unlikely that exactly the same CNV will occur twice, while it sometimes happens that the same SNV occurs more than once. Thus, finding the same CNV in Melanesians and in denisovans, but not in African or Eurasian or American populations or in “non-human” monkeys is conclusive evidence that CNV originated in denisovans and was introgressed in Melanesians.

This analysis led to the identification of inherited Neanderthal and denisovan CNVs associated with adaptive selection, including CNVs related to diet, metabolism, immunity, and cellular functions. The researchers also found two previously unknown genes, one from Neanderthals and one from denisovans.

Our results collectively show that large CNVs originating from archaic hominins and introgressed in modern humans have played an important role in local population adaptation and represent an under-researched source of large-scale genetic variation, the study authors wrote.

The researchers believe these introgressed CNVs were mutations that were positively selected for in Neanderthals and Denisovans, meaning the genetic changes boosted their fitness to survive and reproduce. But the team cant know for certain; they were unable to assess the actual biological functions of their genes because they went extinct around 35,000 years ago, said Hsieh. Importantly, Hsieh said a full understanding of the true functional impacts of these new genes will require additional work. Indeed, not knowing the precise consequences of these inherited CNVs represents a major limitation of the new paper. Now that theyve been identified, however, scientists can explore further.

Understanding the actual function and their beneficial effects requires different types of data and analysis that are beyond the scope of this study, SEH told Gizmodo. We look forward to working with other scientists and Melanesian people to better understand the biology of these variants and advance our understanding of the evolution of our species.

That these mutations have provided an evolutionary advantage to certain populations is a distinct possibility. Previous studies have shown that a mutation derived from denisovans allowed ancient Tibetans to thrive at high altitudes, particularly the ability to prevent hypoxia or low oxygen levels. This could have happened to the ancient Melanesians, who acquired adaptive traits that allowed them to thrive in an island environment.

This new study, while incomplete, will serve as an inspiring springboard for future research. Interestingly, this study will not just tell us new things about ourselves, but will shed new light on our extinct cousins.