Ancient Immunity:
The Role of an Ancestral Gene in the Fight Against COVID-19
NATALIE DZIKOWSKI `22
Viral infections have posed a challenge to human survival since the Homo sapiens species first evolved. In fact, researchers hypothesize that viruses have been around for billions of years, long before their future human hosts (1). Long before modern medical practices became widespread, the molecules and cells of the human immune system rose to the challenge of fighting viral infections. One of those molecules was OAS1, an enzyme involved in a pathway that inhibits viral replication (2). There is support for the hypothesis that certain variants of this enzyme had been introduced into the Homo sapiens species through mating events with Neanderthals thousands of years ago (3). It has been conserved in humans and primates this whole time, humbly executing its vital role in immunity (4). OAS1 has been investigated for its interactions with many different RNA viruses. Recently, it has made a comeback in scientific literature regarding its role in the COVID-19 immune response. OAS1 is an enzyme, or a protein that helps catalyze chemical reactions, and it is encoded by a gene on chromosome 12 (4). This enzyme has not acted alone; it actually belongs to a whole family of 2’-5’ oligoadenylate synthetases, or OASs. OASs are able to recognize when RNA viruses, such as coronaviruses, trespass into a cell. These viruses are categorized by the type of genetic material they carry, called ribonucleic acid or RNA. It is this genetic molecule, specifically double-stranded RNA, that OAS1 can recognize and bind to when a virus en-
ters a host cell. Once OAS1 is alerted to this threat, it communicates with its sidekick: another enzyme called RNase L. OAS1 quickly catalyzes a reaction that generates 2’-5’ oligoadenylate, a long molecule made up of modified adenosine nucleotides (2). This molecule, in turn, binds to RNase L, inducing a change in its overall structure. This shape change enables it to cut up the double-stranded RNA into small pieces, rendering it unusable by the virus. Ultimately, RNase L prevents the virus from replicating within its host and attacking more host cells (2). In essence, RNase L is the fighter, while OAS1 arms it with what it needs to fight. Together, they have executed an extremely important, yet behind-the-scenes molecular mechanism in the body’s response to viral infections. In fact, this immunoprotective response may have benefitted our ancestors 100,000 years ago, when Homo neanderthalensis — the Neanderthal — and Homo sapiens coexisted (3). Neanderthals and Homo sapiens are classified as different species, and their genomes have slightly different versions of the same genes, called variants. Variants in genes that code for proteins, like OAS1, can actually result in major changes in structure and function of that protein. Depending on the significance of the protein’s function, this may ultimately lead to variations in broader physiological responses. When Homo neanderthalensis and Homo sapiens first diverged into different species, the majority of Neanderthal genetic
Just as p46 may have helped our ancestors hundreds of thousands of years ago, it may be aiding certain populations in fighting COVID-19 infection today.
40
