One of the most interesting questions of hominin evolution is exactly how much of our vanished cousins remains in us. Between 1-4 percent of the modern human genome is derived from Neanderthals everywhere but sub-Saharan Africa. In addition, between 4-6 percent of the modern Melanesian genome has been shown to be derived from a separate species of archaic hominin, Denisovans. Now, a new paper focused on comparing a specific type of genetic variance has found evidence suggesting that Denisovans and Neanderthals made large-scale, long-term positive contributions to the human genome. Our understanding of the impact of these changes is currently limited, but they occur in a rather interesting place.
Most of the studies that compare differences in human populations (or differences between archaic and modern hominins) focus on adaptive single-nucleotide variants (SNV). It was a single nucleotide variation that gave archaic northwest Europeans the ability to digest lactose, and the ability to do so is a textbook case of human natural selection. The image below shows the prevalence of adult lactase persistence as a percentage of the total population.
Single nucleotide variations found in the genome of the Tibetan people are associated with greater acclimatization to high-altitude conditions. These originated in the Denisovan genome. While the Denisovan addition occurred much earlier than the adaptation for adult lactase digestion, both of them have been conserved (meaning they have persisted since initial evolution).
This new research isn’t focused on SNVs. Instead, it analyzed the modern Melanesian genome for signs of copy number variants (CNVs). Copy number variation is when the number of copies of an entire gene are different between individuals. Huntington’s disease, for example, is caused when a specific sub-section of the Huntington gene is repeated to the point that it causes altered protein production. CNVs are much larger than SNVs and they tend to exert very strong selective pressure. Any evidence of conserved CNVs in the Melanesian population that could be traced to the Denisovan or Neanderthal genomes would, therefore, be evidence that these variants conferred benefits.
One thing to know up front is that the impact of CNVs on the human genome is an active field of study. SNVs have historically received far more attention. The discovery of conserved CNVs in the Melanesian population from archaic Denisovan and Neanderthals is significant in its own right. It’s still not clear, however, exactly what either variation actually does. Part of the difficulty of analyzing CNVs is the fact that they’re much larger than SNVs with a much larger range of potential effects.
The researchers found two specific CNVs — one associated with the Denisovan genome, and one associated with Neanderthals. 79 percent of Melanesians carry a duplication on chromosome 16p11.2 of >383,000 base pairs (kbp) that originated from Denisovans and was introduced into the native population 60,000-170,000 years ago.
The second variation was introduced by Neanderthals and is carried by some 44 percent of modern Melanesians. It’s located on chromosome 8p21.3 and consists of a ~6-kbp deletion and a ~38-kbp duplication.
What’s particularly interesting about the Denisovan addition to the human genome is its location. According to the researchers, the specific area of 16p11.2 they identified as being Denisovan in origin is part of a locus which “exhibits an enrichment of complex recurrent structural rearrangements, which predisposes humans to the second most common genetic cause of autism, accounting for ~1% of patients.” To be more specific, the Denisovan CNV is directly adjacent to the area of the chromosome where genes known to be associated with autism are.
This specific section of the human genome is known to be unstable and prone to breakage errors. Previous research on 16p11.2 has found that an earlier duplicative transposition of the BOLA2 gene some 282,000 years ago “simultaneously increased copy number of a gene associated with iron homeostasis and predisposed our species to recurrent rearrangements associated with disease.”
The fact that the Denisovan contribution to the human genome is 1). Huge 2). Built in the metaphorical swamp of 16p11.2, and 3). Highly conserved suggests it was important to retain. The Neanderthal CNV encompasses TNFRSF10D (tumor necrosis factor receptor superfamily 10D). According to the researchers, “TNFRSF10D has been reported as one of the primate-specific genes preferentially expressed in progenitor cells of the human fetal neocortex.”
Honest answer: Nobody is sure. The researchers theorize that these genes likely conveyed an evolutionary benefit to the Melanesians, probably one linked to their lives in an isolated tropical environment.
“Our results collectively suggest that large CNVs originating in archaic hominins and introgressed into modern humans have played an important role in local population adaptation and represent an insufficiently studied source of large-scale genetic variation,” the study authors wrote.
The problems with CNV analysis have made it difficult to apply until now. The application of these techniques suggests we may see them used more widely in the future, but the newness of the approach means we’ll be figuring out what these variances do for quite some time to come.