Regionally specific and highly pleiotropic loci together mediate skeletal evolution in tropical and temperate house mice

Abstract

When organisms are exposed to new environments, they often evolve a suite of adaptive phenotypic changes. Understanding the genetic basis of these changes gives us insight into the factors that constrain and facilitate the process of adaptation. Here we use quantitative trait locus (QTL) mapping in wild-derived house mice from temperate and tropical environments to describe the genetic architecture of adaptive skeletal evolution. This study provides a unique view into the evolution of discordant phenotypic changes within the interconnected skeletal system, since tropical and temperate mice have evolved under the opposing forces of Allens and Bergmanns rules (shorter extremities, but larger body size in cold climates). We generated an F3 mapping population of 449 mice and measured a variety of cranial and post-cranial skeletal traits. First, we discovered that temperate and tropical house mice have undergone extensive skeletal divergence in accordance with Allens and Bergmanns rules. Warm-adapted mice have longer limbs, longer pelvic girdles, longer and narrower skulls, but smaller overall body size. Second, we identified 83 QTL across 13 traits and found that the genetic basis of skeletal divergence involved mainly additive, small-effect loci distributed across the genome. While most QTL influenced only one or two traits, we also identified several highly pleiotropic QTL that influenced multiple traits across the skeletal system, often antagonistically to the evolved difference. Such pleiotropic loci may constrain adaptation. Lastly, we found that QTL for overall skeletal variation were enriched for signatures of selection in wild house mouse populations, providing evidence that skeletal variation in this system is indeed driven by adaptive evolution. Article SummaryThe incredible diversity of the vertebrate skeleton offers an opportunity to explore the genetic architecture of phenotypic variation, which is essential to understanding the process of evolution. We characterize the genetic basis of morphological evolution using QTL mapping in house mice adapted to differing climates. Skeletal divergence is widespread in these mice and reflects temperature adaptation. This divergence is mediated by small-effect loci scattered across the genome, as well as several highly-pleiotropic loci. Interestingly, pleiotropic loci often influence phenotypes in the opposite direction from the evolved change, perhaps constraining the process of adaptation. This work demonstrates how complex morphological changes can evolve within an interconnected system, such as the skeleton, under functional, developmental, and selective constraints.