Discovery of a selfish supergene's dispersal phenotype in house mice Mus musculus domesticus

Abstract

The organism and its genome are a remarkable cooperative achievement of billions of DNA bases that work together. Natural selection has shaped the genome into cooperation by generally favoring those genomes that work well as a whole, rather than resembling collections of genes that do not produce anything greater than the sum of their parts. But what seems perfectly harmonious is actually the site of an ever-lasting struggle over transmission from one generation to the next. This struggle is only contained by the benefits that cooperation accrues for each genetic element. In organisms with two sets of chromosomes, each gene is only transmitted to half of all offspring, but from the perspective of the gene, it would be much preferable if it was transmitted to all. Consequently, some genes manipulate that process and increase their own transmission to the detriment of the genes that are thereby transmitted less often as well as the rest of the genome. The t haplotype in house mice is such a selfish actor in the genome of house mice that carry it. It is a collection of linked genes, a supergene, that makes up 1% of the house mouse genome. It increases its own transmission from male carriers to their offspring to over 90%, rather than the expected 50%. However, not every mouse carries the t supergene, which puzzled biologists given its increased rate of transmission. This is due to the t's two strongly disadvantageous traits. First, mice that carry the t haplotype on both chromosomes are either infertile as males or completely inviable. This immediately puts an upper limit on the frequency of the t haplotype in any population, because at a minimum not all mice can carry it on both chromosomes. However, this disadvantage alone would still allow for high frequencies of the t, but that is not what is found in nature. The second disadvantage of the t is likely a consequence of the mechanism with which it increases its own transmission. The t increases its transmission using a poison-antidote mechanism; it poisons all sperm of its carrier, but there is an antidote in the sperm thatcarry thet, thus only sperm that do not carry thetshould be harmed. However, t‐carrying sperm are negatively impacted by this poison‐antidote mechanism,as well, but to a lesser degree. The damage caused by this mechanism comesinto full effect whent‐carrying males are mating with females who also matewith other males in the same estrus cycle. This constellation creates competi‐tion between the sperm of the different males that mated with the female. Insperm competition,t‐carrying males are much less successful in fertilizing thefemale than males who do not carry thet. This second disadvantage is so strongthat it could explain the very low frequencies of thetin the wild. In very densepopulations, where sperm competition is more common due to more matingsper estrus cycle, thetcan even go extinct, opening the question why thethasnot gone extinct completely.

In this thesis, I am introducing, testing, and verifying the hypothesis that the t haplotype increases the probability with which t-carriers emigrate from populations to settle elsewhere, a process known as dispersal. Dispersal is a dangerous behavior, which is why the costs and benefits of it have shaped individual propensity to disperse over evolutionary time. Thus, a deviation from "normal" odds of dispersal could be against the interest of the organism as a whole. In Chapter 1, I introduce the reader to the broader picture of the conflict between genes within an individual's genome. In Chapter 2, I describe the hypothesis that t-carriers should be more dispersive than mice who do not carry the t, because this way the t is better equipped to avoid populations in which its disadvantageous traits are most pronounced. I tested this hypothesis using an intensively studied population of house mice and found an increased number of t-carrying mice emigrating from the population. In Chapter 3, I investigate the evolution of increased dispersal more formally using computer simulations. I find that the two disadvantageous traits of the t, inviability when carried on both chromosomes and poor performance in sperm competition with other males, indeed select for increased dispersal. However, the increased transmission alone is not sufficient to evolve increased dispersal. In Chapter 4, I verify the hypothesis using controlled experimental setups and I furthermore find that t-carriers are also heavier, more likely to disperse at higher weights, and more prone to explore unknown areas than mice who do not carry the t, which are all traits that could be beneficial for mice who are more likely to disperse. I conclude that the t haplotype appears to produce a remarkable dispersal phenotype in the mice that carry the t, which is a rare finding that should combine very well with the t's increased transmission. Finally, in Chapter 5, I provide an outlook on work towards understanding the genetic basis of the t's influence on dispersal. I describe a novel adaptation of a statistical method that allows usto gain insights into the genome sequences of mice much more cost‐efficientlythan what used to be possible, which will enable us to study the genetic basis ofdispersal in house mice.