Genetics of Skeletal Evolution in Unusually Large Mice from Gough Island

Organisms on islands often undergo rapid morphological evolution, providing a platform for understanding mechanisms of phenotypic change. Many examples of evolution on islands involve the vertebrate skeleton. Although the genetic basis of skeletal variation has been studied in laboratory strains, especially in the house mouse Mus musculus domesticus, the genetic determinants of skeletal evolution in natural populations remain poorly understood. We used house mice living on the remote Gough Island-the largest wild house mice on record-to understand the genetics of rapid skeletal evolution in nature. Compared to a mainland reference strain from the same subspecies (WSB/EiJ), the skeleton of Gough Island mice is considerably larger, with notable expansions of the pelvis and limbs. The Gough Island mouse skeleton also displays changes in shape, including elongations of the skull and the proximal vs. distal elements in the limbs. Quantitative trait locus (QTL) mapping in a large F-2 intercross between Gough Island mice and WSB/EiJ reveals hundreds of QTL that control skeletal dimensions measured at 5, 10, and/or 16 weeks of age. QTL exhibit modest, mostly additive effects, and Gough Island alleles are associated with larger skeletal size at most QTL. The QTL with the largest effects are found on a few chromosomes and affect suites of skeletal traits. Many of these loci also colocalize with QTL for body weight. The high degree of QTL colocalization is consistent with an important contribution of pleiotropy to skeletal evolution. Our results provide a rare portrait of the genetic basis of skeletal evolution in an island population and position the Gough Island mouse as a model system for understanding mechanisms of rapid evolution in nature.