Maybe a Genetic Bottleneck Followed by Rapid Expanision Is Just a Genetic Bottleneck Followed by Rapid Expanision?

Many, many moons ago, when I was a wee Mad Biologist, and a graduate student in a ‘unified’ biology department (which wasn’t very unified at all…), one contentious issue was the insistence by many of the molecular biologists that, if they observed an amino acid change in protein, it meant that selection had acted on it, while the evolutionary biology wing of the department would argue that most amino acid changes were neutral (i.e., they wouldn’t affect the fitness of the organisms with that variant).

Like I said, this was a long time ago, and there is considerable consensus that, if you see a change, don’t automatically assume it’s due to natural selection (if you’re interested in this topic, this post might explain this issue more).

So, earlier this week, the LA Times breathlessly reported the findings of a pre-print arguing that the SARS-CoV2 virus has evolved to become more transmissible. Slow down there, Sparky! (boldface mine):

A preliminary scientific paper on covid-19—detailed by the Los Angeles Times on Tuesday—is sure to unnerve people. It argues that the world is now dealing with a mutated, more contagious form of the coronavirus that causes covid-19 than the version that originated in China…

The team noticed that samples of the original strain in Wuhan, China sometimes carried a certain mutation in the spike protein, called D614. Many of the earliest cases in Europe, the U.S. and elsewhere also carried D614. In late February, however, another form of the mutation, called G614 (or D614G) began cropping up. And in almost every region, starting with Europe, the team saw a familiar pattern in their studied samples: the G614 form of the virus would show up and quickly supplant the D614 form, sometimes in a matter of weeks.

This rapid spread of the G614 version of the virus, the authors argued, demonstrates “the emergence of a more transmissible form of SARS-CoV-2.”

…“The great majority of sequenced isolates now descend from the European outbreak, which has spread more extensively than the Chinese one. That could be because it is more transmissible, but it could also be because the relatively late interventions allowed it to spread more,” Hanage told Gizmodo.

In other words, the G614 mutation may not have any effect on how contagious the virus is; it might have just hitched a ride onto strains of the virus that were spread from Europe to everywhere else. And while Hanage does think that the authors have some interesting evidence suggesting the mutation could plausibly improve the virus’s ability to spread, it’s not conclusive.

Angela Rasmussen, a virologist at Columbia University, is even more skeptical of the team’s conclusions than Hanage.

“They didn’t do a single experiment, and this is all conjecture,” she told Gizmodo. “There’s no indication that this mutation makes the virus more transmissible, and they’ve done nothing to show that this mutation is functionally significant.”

In other words, what looks like a selective sweep of the G614 mutation containing viruses over the D614 viruses might be something very different. Instead, by chance, the G614 viruses might have been first to Europe, and then spread rapidly there. If the D614 arrived later–and at some point, the source D614 population in China might have stopped arriving at all due to travel restrictions–then the G614 would ‘win.’ (Bill Hanage lays this out in more detail here).

Without functional information, it’s difficult to distinguish between natural selection leading to the sweep of a variant, and a genetic bottleneck (i.e., only G614 isolates made it initially) followed by massive expansion (the massive spread in Europe). That said, it seems like there might be something interesting going on with the L5F and S943P mutations, though, those too, need to be checked.

Anyway, just somethings to consider before we freak out even more.

This entry was posted in COVID-19, Genetics. Bookmark the permalink.