Some Neandertal Genes in People Today May Protect Against Severe COVID-19
18 Feb 2021 8:38 PM
A new study looked at a stretch of DNA on chromosome 12 where a haplotype — a cluster of genetic variants that are inherited together — that affects susceptibility to the coronavirus is located. For each copy of the Neandertal haplotype a person inherited, the risk of needing intensive care fell approximately 22 percent, researchers report in the March 2 Proceedings of the National Academy of Sciences.
The variants may affect the activity or function of genes involved in a biochemical chain reaction that ends with the destruction of viral RNA, including the coronavirus’s. The protective variants are largely absent among people in sub-Saharan Africa, where few people carry genes inherited from Neandertals. About 25 to 30 percent of present-day people of Asian and European ancestry carry the protective variants. Some Black people in the Americas also inherited the protective haplotype, presumably from Asian, European or Native American ancestors.
You can read more at https://www.pnas.org/content/118/9/e2026309118.
The Proceedings of the National Academy of Sciences (PNAS), the official journal of the National Academy of Sciences (NAS)
A genomic region associated with protection against severe COVID-19 is inherited from Neandertals
PNAS March 2, 2021 118 (9) e2026309118; https://doi.org/10.1073/pnas.2026309118
Contributed by Svante Pääbo, January 22, 2021 (sent for review December 21, 2020; reviewed by Tobias L. Lenz and Lluis Quintana-Murci)
It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is inherited from Neandertals. New, larger genetic association studies now allow additional genetic risk factors to be discovered. Using data from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease. It also differs from the risk haplotype in that it has a more moderate effect and occurs at substantial frequencies in all regions of the world outside Africa. Among ancient human genomes in western Eurasia, the frequency of the protective Neandertal haplotype may have increased between 20,000 and 10,000 y ago and again during the past 1,000 y.
Neandertals evolved in western Eurasia about half a million years ago and subsequently lived largely separated from the ancestors of modern humans in Africa (1), although limited gene flow from Africa is likely to have occurred (2⇓⇓–5). Neandertals as well as Denisovans, their Asian sister group, then became extinct about 40,000 y ago (6). However, they continue to have a biological impact on human physiology today through genetic contributions to modern human populations that occurred during the last tens of thousands of years of their existence (e.g., refs. 7⇓⇓–10).
Some of these contributions may reflect adaptations to environments outside Africa where Neandertals lived over several hundred thousands of years (11). During this time, they are likely to have adapted to infectious diseases, which are known to be strong selective factors that may, at least partly, have differed between sub-Saharan Africa and Eurasia (12). Indeed, several genetic variants contributed by archaic hominins to modern humans have been shown to affect genes involved in immunity (e.g., refs. 7, 8, 13, 14). In particular, variants at several loci containing genes involved in innate immunity come from Neandertals and Denisovans (15), for example, toll-like receptor gene variants which decrease the susceptibility to Helicobacter pylori infections and the risk for allergies (16). Furthermore, proteins interacting with RNA viruses have been shown to be encoded by DNA regions introgressed from Neandertals more often than expected (17), and RNA viruses might have driven many adaptive events in humans (18).
Recently, it was shown that a haplotype in a region on chromosome 3 is associated with becoming critically ill upon infection with the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) (19) and was contributed to modern humans by Neandertals (20). Each copy of this haplotype approximately doubles the risk of its carriers requiring intensive care when infected by SARS-CoV-2. It reaches carrier frequencies of up to ∼65% in South Asia and ∼16% in Europe, whereas it is almost absent in East Asia. Thus, although this haplotype is detrimental for its carriers during the current pandemic, it may have been beneficial in earlier times in South Asia (21), perhaps by conferring protection against other pathogens, whereas it may have been eliminated in East Asia by negative selection.
A new study from the Genetic of Mortality in Critical Care (GenOMICC) consortium, which includes 2,244 critically ill COVID-19 patients and controls (22), recently became available. In addition to the risk locus on chromosome 3, it identifies seven loci with genome-wide significant effects located on chromosomes 6, 12, 19, and 21. Here, we show that, at one of these loci, a haplotype associated with reduced risk of becoming severely ill upon SARS-CoV-2 infection is derived from Neandertals.