Breathless: The Scientific Race to Defeat a Deadly Virus

by David Quammen

Did evolutionary selection favor all of Omicron’s significant changes individually, amino acid by amino acid, or did it favor them as a bundle—for their combined effect, their intricate interaction, their collective bottom line? The second of those propositions, as Martin and his coauthors noted, has a fancy name in genetics: positive epistasis. This concept is simple (only the details are complex). Epistasis refers to the interactive effects of genes in different parts of the genome, playing off one another or harmonizing, like instruments in different parts of an orchestra. A mutation inclined to have neutral or even negative impact individually may perform a beneficial function when that gene interacts with others. Further, the effect of one mutated gene may depend on the presence or absence of mutations in other genes. Positive epistasis in the context of Omicron means that multiple mutations are enhancing the adaptive value of one another. This variant, with its many mutations, may be a creature in which great intricacies of epistasis are making it more formidable. Kristian Andersen has a postdoc in his lab, Edyth Parker, who put it more vividly when she said that “the epistatic fucking cirque du soleil of this virus is discombobulating.”