Where Variants Come From

The Greek alphabet is getting tired, and mother nature is not. There will be more variants. Normally, viral evolution follows a single line, each new most competitive variant being a direct descendant of the last, taking on its ancestors characteristics. 

To some extent, SARS-CoV-2 also acts in this way, like “BA.2,” a further evolution in the Omicron lineage, which recently made headlines. There are already over 800 distinct Omicron descendants. But the variants that get the shiny new Greek names, the capitol-V variants, are often unrelated. Omicron and Delta for example last shared a known ancestor before the first Covid case in the United States. 

Viral competition is fierce. Variants of a virus tend to generate immunity against one another, which raises the stakes. If one variant spreads faster, the other variants will have fewer to infect, and depending on how much faster the variant spreads, it may even make the older form go extinct. The Delta variant’s competition saw the extinction of practically every other Covid variant in humans. Now due to Omicron, this script has been flipped, and the Delta variant is practically extinct. There are currently under a hundred cases of it worldwide. 

So why haven’t new Covid variants been direct descendants of one another? How is it possible for the new variant to be a descendant of an extinct virus?

Variants typically come about in 3 ways: normal evolution, an immunocompromised human host, or reverse zoonosis. The same evolutionary principles that apply to all other animals also apply to viruses, just on a smaller scale. The accumulation of advantageous mutations can, over much time, result in a new variant. 

In the second route, the virus infects someone who has an immune capacity high enough to control the virus, but not enough to clear the infection completely. So the virus replicates, churns in their respiratory system at low levels for potentially months, and gets a free training ground against the human immune system. At some point, enough mutations accumulate that the virus can reinfect an immunocompetent host, and a variant is born. This process created the variants before Delta, and possibly Delta itself. New variants were not related to one another because, before Delta, genetic diversity was great enough, and the virus was new enough, that each of the roughly half-dozen lineages were producing their own most successful progeny.

Zoonotic, in the context of viruses, refers to viruses that originate in animals that can infect humans. Reverse zoonosis, then, is a human virus infecting an animal. Zoonotic viruses make waves because they are maladapted to humans, which paradoxically can be dangerous. Human immune systems are adapted to human viruses, a virus that gives a cold to a cow could kill a human. 

Zoonotic viruses, while scary, are mercifully rare. The conditions within an organism that allow a virus to replicate inside it are incredibly sensitive and specific, it goes without saying that the change of a whole species makes a dramatic difference. One of SARS-CoV-2’s most unique characteristics is its record-breaking generalism, able to infect dozens of mammals. Bats and humans, obviously, but also mice, wild and domestic cats, gorillas, mink, hamsters, pangolin, deer are only some of the known susceptibles, as well as whatever else has yet to be recorded. 

While SARS-CoV-2 may be able to infect mink or cats or whatever, the human-adapted forms of the virus are not going to be the best adapted to that animal. Considering animals do not observe social distancing, the virus still moves through their populations quickly despite the hostile environment, accumulating advantageous mutations as it goes. The all too familiar viral competition that has been happening in humans has also been happening in a half dozen different animal species with the same virus, and now their apex predators are spilling back over. Canadian researchers recently identified a new variant in white-tailed deer with 76 total mutations that last shared ancestors with human virus lineages sometime in fall 2020. For reference, Omicron has 60-80. These animal-bred variants are not adapted to humans, so the human variants generally outcompete them in the human population. The Omicron variant is the rare exception, likely originating in mice.