Genetics and Evolution of Hybrid Male Sterility in House Mice

Abstract

Comparative genetic mapping provides insights into the evolution of the reproductive barriers that separate closely related species. This approach has been used to document the accumulation of reproductive incompatibilities over time, but has only been applied to a few taxa. House mice offer a powerful system to reconstruct the evolution of reproductive isolation between multiple subspecies pairs. However, studies of the primary reproductive barrier in house mice-hybrid male sterility-have been restricted to a single subspecies pair: Mus musculus musculus and Mus musculus domesticus. To provide a more complete characterization of reproductive isolation in house mice, we conducted an F 2 intercross between wild-derived inbred strains from Mus musculus castaneus and M. m. domesticus. We identified autosomal and X-linked QTL associated with a range of hybrid male sterility phenotypes, including testis weight, sperm density, and sperm morphology. The pseudoautosomal region (PAR) was strongly associated with hybrid sterility phenotypes when heterozygous. We compared QTL found in this cross with QTL identified in a previous F 2 intercross between M. m. musculus and M. m. domesticus and found three shared autosomal QTL. Most QTL were not shared, demonstrating that the genetic basis of hybrid male sterility largely differs between these closely related subspecies pairs. These results lay the groundwork for identifying genes responsible for the early stages of speciation in house mice.

The Pace of Hybrid Incompatibility Evolution in House Mice

“…We used data from two studies that mapped QTL for hybrid male sterility between wild-derived inbred strains from the three subspecies of house mice: M. m. musculus (PWD/PhJ) and M. m. domesticus (WSB/EiJ) ) and M. m. castaneus (CAST/EiJ) and M. m. domesticus (WSB/EiJ) (White et al 2012a). These studies quantified five morphological traits strongly correlated with male fertility: testis weight, sperm density, proportion of abnormal sperm, sperm head shape, and stage VII seminiferous tubule area.…”

“…In the first approach, we considered single QTL identified by standard interval mapping in White et al (2011White et al ( , 2012a. For each QTL peak, we examined the physical positions of the maximum LOD score and the 1.5-LOD interval.…”

“…Our QTL analysis used data from previously published studies (White et al , 2012a. Sequences used to estimate the subspecies trees and branch length are from Keane et al (2011).…”

“…The three subspecies diverged recently (Geraldes et al 2008(Geraldes et al , 2011White et al 2009;Duvaux et al 2011), perhaps ,350,000 years ago (Geraldes et al 2011). Two pairs of subspecies show partial reproductive isolation, particularly in the form of hybrid male sterility (Forejt and Iványi 1974;Britton-Davidian et al 2005;Vyskočilová et al 2005;Good et al 2008a;White et al 2012a), indicating speciation is in progress. House mouse subspecies also hybridize in the wild (Boursot et al 1993;Sage et al 1993;Duvaux et al 2011;Jing et al 2014), providing opportunities to connect the genetics of reproductive isolation phenotypes in the laboratory with gene flow in nature.…”

Disproportionate Roles for the X Chromosome and Proteins in Adaptive Evolution

“…Genetic studies of hybrid male sterility-the primary reproductive barrier between house mouse subspecies-support this prediction. Loci that cause F 2 sterility in crosses between M. musculus castaneus (the subspecies studied by Kousathanas et al (2014)) and M. musculus domesticus map differentially to the X chromosome (White et al 2012) and multiple X-linked loci shape F 1 and F 2 sterility in crosses between M. musculus domesticus and M. musculus musculus (Storchova et al 2004;Good et al 2008;White et al 2011). Interestingly, disruptions in MSCI are also connected to hybrid male sterility in house mice (Campbell et al 2013).…”