This guest post is by Russ Corbett-Detig, Emily Jacobs-Palmer, and Hopi Hoekstra (@hopihoekstra) on their paper Corbett-Detig et al Segregation distorters are not a primary source of Dobzhansky-Muller incompatibilities in house mouse hybrids bioRxived here.
What are segregation distorters and how can they contribute to reproductive isolation?
Within an individual, somatic cells are typically genetic clones of one another; in contrast, haploid gametes are related to their compatriots at only half of all loci on average, opening doors to intra-individual competition and conflict. Eggs and sperm may express selfish genetic elements called segregation distorters (SDs) that disable or destroy competitor gametes carrying unrelated alleles. The resulting transmission advantage attained by SDs allows them to invade populations without improving the fitness of individuals that harbor them. Indeed, SDs often negatively impact carriers’ fitness because such hosts transmit fewer fit (or viable) gametes. Hence natural selection favors the evolution of alleles that suppress distortion and thereby restore fertility.
Coevolution of SDs and their suppressors can in turn contribute to the evolution of reproductive isolation between diverging lineages. How? If two populations become temporarily isolated from one another, SDs and later their accompanying suppressors may arise and eventually fix in one isolated population, possibly multiple times over. Should the two populations then encounter each other again, the sperm of hybrid males, for example, will contain one or more distorters without the appropriate suppressors, and these males will suffer decreased fertility. Over time, gene flow may be substantially and perhaps permanently hindered leading to the formation of two reproductively isolated species.
In some Drosophila species pairs, and in many crop plants, it is clear that the coevolution of SDs and their suppressors are major, even primary, contributors to the evolution of reproductive isolation between diverging lineages. At present, however, the relative importance of SDs-suppressor systems to reproductive isolation in broader taxonomic swathes of sexually reproducing organisms (e.g. mammals) is largely unexplored.
Our solution to the practical challenges of studying SDs
The primary impediment to addressing this important question in evolutionary biology is practical, not conceptual. Conventionally, researchers detect SD-suppressor systems by crossing two strains to produce a large second-generation hybrid population; they then genotype these hybrids at a set of markers across the genome to identify loci that show substantive deviations from 50:50 mendelian ratios—putative SDs. Ultimately, this traditional approach suffers from two major pitfalls. First, for many organisms it is not feasible to raise and genotype enough hybrids (hundreds to thousands) to have sufficient statistical power to detect SDs, especially those with weaker effects. Second, by genotyping these second generation hybrids, rather than the gametes of their parents, one conflates SD with hybrid inviability, and it can be very difficult to disentangle these two factors.
How to circumvent these challenges? In this work, we develop an alternative approach that avoids these practical challenges. We first obtain high quality, motile sperm from first generation hybrid males (generated from two strains with available genome sequences), and then sequence these sperm in bulk as well as a somatic ‘control’ tissue. We then contrast the relative representation of the parental chromosomes in windows across the genome in both samples, searching for regions where the sperm allele ratios show more DNA copies of one parental haplotype, but the somatic alleles do not. Importantly, this approach is very general, and it can easily be applied to any number of interspecific or intraspecific crosses where it is possible to obtain large quantities of viable gametes.
Little evidence for SDs in house mouse hybrids
We apply this method to a nascent pair of Mus musculus subspecies,M. m. castaneus and M. m. domesticus. We chose these subspecies because hybrid males formed in this cross are known to be partially reproductively dysfunctional. Nonetheless, using our novel method we find no evidence supporting the presence of SDs—no genomics regions showing a statistical deviation from 50:50 compared to control tissue—despite strong statistical power to detect them. We conclude that SDs do not contribute appreciably to the evolution of reproductive isolation in this nascent species pair. Instead, reproductive isolation in these mammalian subspecies likely stems from other incompatibilities in spermatogenesis or ejaculate production unrelated to SD-suppressor coevolution.
So what’s next? Because this approach—bulk sequencing of sperm from hybrid males—can be used on almost any pair of interfertile taxa, we can begin to better understand the prevalence of SD and its role in speciation in a wide diversity of species.