In a previous post, I described one of our first-semester courses where we dissect and propose followup studies for one (or sometimes more) papers every week. The course also requires us to write two formal mini-proposals to build upon papers from any two weeks. This is meant to prepare us for our qualification exams at the end of the first year, where we write a proposal to build on an assigned paper.
While most weeks focused on cellular/molecular concepts such as gene regulation, non-coding RNA, and development, we have finally gotten to population genetics in these last two weeks. This week’s paper shows, through simulations, that the answer to the question in the title is, quite counter-intuitively, yes, in a specific context which will I get to later. I am writing my second mini-proposal on this paper.
Why is it counter-intuitive? High genetic diversity is generally thought to be indicative of a healthier population. Not only does the greater genetic variation make it more likely that the population can adapt to changing conditions, it also masks recessive, deleterious variants and prevents inbreeding depression. Inbreeding depression is when individuals in a small population have lower fitness due to low genetic diversity resulting from inbreeding. Think Joffrey from Game of Thrones.
Conservation efforts increasingly adopt a genetic rescue approach, where individuals from a large population are introduced into an endangered small population in an effort to increase genetic diversity into the endangered population and prevent inbreeding depression and extinction. Large populations generally contain more genetic diversity, which is thought to be ideal for such efforts. Kyriazis et al., however, point out that the introduction of a migrant gray wolf individual from a large population into an endangered population on Isle Royale appeared to have the opposite of the desired effect by contributing to population collapse. They therefore designed simulations to explore the fate of small populations rescued or founded by individuals from large vs. small populations.
The simulations demonstrate that larger populations do end up with higher genetic diversity but also accumulate a larger number of strongly deleterious recessive alleles, which remain masked because most individuals are outbred and heterozygous. They also fascinatingly predict that a small founder population derived from a large, more genetically diverse population would have a lower time to extinction than one derived from a relatively smaller, less genetically diverse population. This is because when a large population suddenly contracts (that is, when you derive a small subset of individuals from the large population), the deleterious recessive alleles become unmasked as the frequency of homozygotes increases over generations due to interbreeding between the small set of individuals.
While the simulations and their predictions are compelling, and should be taken into account when considering genetic rescue in future conservation efforts, one limitation of their underlying model is that it assumes that all mutations are either selectively neutral (meaning they have no effect on an individual’s fitness), or deleterious. Beneficial mutations, while supposedly rarer, do occur, and spread faster through larger populations. This is because large populations are less susceptible to random fluctuations of the frequencies of genetic variants. In small populations, even a beneficial mutation is likely to be lost for reasons unrelated to fitness, but due to chance events such as an individual not finding a mate. Here’s a great demonstration of the effects of selection in a large population in the context of another counter-intuitive extinction story.
It would be interesting to see how incorporating a small rate of beneficial mutations affects the predictions of Kyriazis et al.’s model. That is, at any rate, half of my mini-proposal to build on this paper.
The Genome Inquirer 