A German study identifies the presence of Neanderthal genes as the cause of deadly side-effects in Coronavirus infection: South Asians at the highest risk!
COVID-19; the highly transmissible disease caused by the virus SARS-CoV-2 has already spreaded over the world, infecting millions of people. Among the infected patients, the development of symptoms ranges from no symptoms to respiratory failure. Even though the age and male gender were considered as the main risk factors during the early days of COVID-19 outbreak, they failed in explaining why only some of them developed severe symptoms while others did not at all. There came the possibility of any association of genetic factors involving disease progression within the individuals. Writing to a Nature article in September, Hugo Zenberg and Svante Paabo of Max Planck Institute for Evolutionary Anthropology, Germany, revealed an outstanding correlation between genetic association and COVID-19 symptom development.
With the data of a previous genetic research and COVID-19 Host Genetic Initiative, they confirmed the presence of a genetic region of 6 genes in the 3rd chromosome of the human genome that is associated with severe symptoms development in COVID-19. This resulted in a major question, ‘whom from these genes entered the genome of present-day humans?’
The genes present in chromosome 3 that are associated with severe COVID-19 were found to have a strong association with each other in the population (higher linkage disequilibrium). Further, this 49.4 kb genetic region; core haplotype (inherited together) was found to process some weaker association (low linkage disequilibrium) with longer haplotypes of about 300 kb in length.
As the ancestors of present-day humans are Neanderthals and Denisovans, undoubtedly these haplotypes of present humans should have inherited from either Neanderthals or Denisovans: extinct hominids. Were they inherited from Neanderthals or Denisovans?
Out of several Neanderthal genomes representing Vindija 33.19 (about 50,000-year-old Neanderthal from Croatia in southern), Altai (about 120,000-year-old Neanderthal from southern Siberia), Chargyrskaya 8 (about 60,000-year-old Neanderthal from southern Siberia) and Denisovan genome, the risk haplotype of 300 kb were only found in Neanderthal genome, but Denisovan. And among 3 different Neanderthals, those who descended from Croatia had more similarity than Siberian descendants.
Omitting the unlikely possibility (based on recombination rules and generation time) of inheriting the risk haplotype of 50 kb from a common ancestor of both Neanderthal and modern human (five hundred thousand years ago), it was concluded that Neanderthals as the genetic source for 50 kb haplotype among modern human.
After analyzing more than 5,000 haplotypes in the interested genome region from the 1000 Genome Project, 253 haplotypes present in today humans were comparatively studied with the genome of Neanderthals. Surprisingly, all the COVID-19 risk haplotypes made a clade (a group of organisms seems to comprise all the evolutionary descendants of a common ancestor) with the 3 Neanderthal genomes, revealing a closer relationship with Vindija 33.19 Neanderthal.
Interestingly, the Neanderthal descended haplotypes are completely absent among the Africans in the 1000 Genome Project, which may be due to the limited or indirect gene flow in between Neanderthals and Africans. However, these haplotypes present in an allele frequencies of 30%, 8% and 4% among the present-day South Asians, Europeans and mixed Americans respectively but in lower frequencies among east Asians.
When this data is manipulated to carrier frequencies, 50%, 16% and 9% of South Asians, Europeans and mixed Americans are carriers to these haplotypes respectively (at least carry one copy (heterozygous)). Interestingly, the highest carrier frequency occurs among Bangladeshi where 63% of the population carries at least one copy of the Neanderthal risk haplotype while 13% of the population is homozygous ( carry two copies).
Accordingly, Neanderthal haplotypes can be considered as a significant contributor to COVID-19 risk in certain populations other than being elderly. The confusing allele frequencies between south and east Asians might be due to past genetic selection. Even though these genes were promoted in evolution as positive selection or drift heretofore, will be negatively selected thereupon.
It is yet unknown what features in these haplotypes make individuals more likely to develop adverse symptoms in COVID-19 or whether these same individuals would react similarly for other pathogens.
