Some genes inherited from Neanderthals help challenge the virus, others are at risk of getting seriously ill

Viruses can only survive and multiply in host cells. Therefore, studying the SARS-CoV-2 virus will require studying the host. As the viral genome takes the help of the host machinery, understanding the host genome is paramount to studying both susceptibility and protection against the virus in a given population. This is the main goal of several international groups and consortia of researchers such as the Severe Covid-19 Genome-wide Association Study Group, the COVID-19 Host Genetics Initiative and the Genetics of Mortality in Critical Care (GenOMICC).

A series of published studies from these consortia shed light on the role of the host genome in viral infection. These studies, published in NEJM, Nature and MedRxiv provide clues as to how certain regions of the host’s genome increase the risk of developing severe disease while others protect against the virus. Thus, studying the genomes of individuals in a group (for example, a particular genetic population group in India) can lead us to predict whether individuals in that group are more or less likely to develop serious disease.

Crucial genes

Recent articles have pointed out that a region on host chromosome 3 acts as an important genetic risk factor for becoming seriously ill and, at the same time, a cluster of genes on chromosomes 6, 12, 19 and 21 protects us from the virus. Of particular importance are the enzymes encoded by the OAS gene family on chromosome 12, a component of the interferon-induced antiviral system, as they can act as a drug target against the virus. An independent study of Canada in Nature medicine corroborated this by showing that a protein of the same component in the blood protects against serious disease among people of European descent.

Interestingly, evolutionary biologists in Sweden and Germany have shown that regions of the host genomes that increase the risk of becoming seriously ill and protect against the virus were inherited from Neanderthals. How can Neanderthal genes both increase the risk of getting severe disease and at the same time protect against the virus?

Once, Neanderthals and modern humans came into contact with each other, and they crossed paths. As a result, the genetic content between Neanderthals and humans mixed in their offspring.

In their first article, published in Nature, researchers have shown that modern humans share an expanse of 50,000 nucleotides (nucleotides are the building blocks of DNA) in chromosome 3 with Neanderthals. It is this stretching that increases their risk of contracting severe COVID-19. They predicted that having a copy of this region of chromosome 3 almost doubles the risk of getting severe COVID-19.

Push-pull effect

The same researchers published a second article in PNAS showing that part of the host’s chromosome 12, which has previously been shown to protect against the virus, is also inherited from Neanderthal genomes. While specific genes in Neanderthals work against the virus and protect us from serious illness, others are associated with an increased risk of becoming seriously ill. This push and pull effect may be one of the intriguing facts about how gene selection occurs during evolution.

These studies are of particular importance for India. About 50% of South Asians carry the chromosome 3 region of the Neanderthal genomes, the same region that makes us more likely to be seriously ill with the virus. On the front of the good Neanderthal gene, nearly 30% of South Asians carry the region of chromosome 12 that protects us from serious disease. As Indians are a diverse genetic group, the above risk was determined using samples previously used in an international consortium called the 1000 Genomes Project. The project is represented by the Indian Gujaratis and Telugus, Pakistani Punjabis and Bangladesh Bengalis in the South Asian group. These recent studies only validate what the legendary evolutionary biologist Theodosius Dobzhansky wrote in his famous essay: “Nothing in biology makes sense except in the light of evolution”, and only makes sense when one think about the evolution of host genomes regarding SARS-CoV-2 infection.

(Binay Panda is professor of biotechnology at Jawaharlal Nehru University, New Delhi.)