Research Reveals Relation of Neanderthal Gene Sequence to COVID-19 Susceptibility

by Christian Natanauan (Ikirara)

A 2020 research published in the online journal Nature by scientists Hugo Zeberg and Svante Pääbo (Karolinska Institute, Sweden and Max Planck Institute for Evolutionary Anthropology, Germany) uncovered association of a Neanderthal gene region on human chromosome 3 to the vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A study by the COVID-19 Host Genetics Initiative found that the inheritance of this Neanderthal gene heightens the probability to be hospitalized with COVID-19 by about 60%. Along with this Neanderthal gene region, studies report that an ABO group-related region on human chromosome 9 causes the same effects. 

The inheritance of the Neanderthal region made up of six genes is due to a detection of high linkage disequilibrium (LD) among the genes (r2 > 0.98). This implies that the Neanderthal haplotypes closely relate to each other in a locus and are more likely to avoid random inheritance, thus being inherited with one another and should allow the expression of the desirable gene trait. High LD can also cause a specific haplotype to rapidly increase in frequency, further enhancing the gene expression of the allele it is carrying. Therefore, higher rates of LD can help determine the heritability of the haplotype in an evolutionary chain which has allowed for the mapping and gene analysis of the Neanderthal gene region.

Through LD calculations and comparisons with haplotypes from the database of the 1000 Genomes Project, genomic information originating from the Neanderthals of Vindija, Croatia are highly related to the present-day Neanderthal gene region that affects COVID-19 susceptibility. Bangladeshi genes had the highest frequency of Neanderthal gene inheritance, with about 63% of the population carrying at least one copy of the haplotype and 13% that are homozygous for the haplotype. Other regions discovered to have inherited high frequencies of the gene are South Asia (50% carry at least one copy, 30% allele frequency), Europe (16% carry at least one copy, 8% allele frequency) and the Americas (9% carry at least one copy, 7% allele frequency). 

The inheritance of this gene region is almost completely absent in African genomes, attesting to the premise that presence of Neanderthals in the continent was not prominent in prehistoric times. Most astonishingly, genomes from East Asia were also almost completely absent of the Neanderthal gene, despite having the highest recorded frequency of Neanderthal population. This implies that specific time events may have led to region-specific negative selection of Neanderthal genes in the East Asia region. They have also found that the positive selection of this Neanderthal risk haplotype brings forth deleterious effects when expressed in a human body system.

Current studies have yet to determine whether the gene region only affects SARS-CoV-2 susceptibility, or if it allows humans to be susceptible to other pathogens as well. Even so, the promising use of modern gene mapping technology can contribute to the determination of further implications of this Neanderthal gene region and may help unravel its association with other dangerous viral agents.