Data from: Using the Mus musculus hybrid zone to assess covariation and genetic architecture of limb bone lengths

Two subspecies of the house mouse, Mus musculus domesticus and Mus musculus musculus, meet in a narrow contact zone across Europe. Mice in the hybrid zone are highly admixed, representing the full range of mixed ancestry from the two subspecies. Given the distinct morphologies of these subspecies, these natural hybrids can be used for genome-wide association mapping at sufficiently high resolution to directly infer candidate genes. We focus here on limb bone length differences, which is of special interest for understanding the evolution of developmentally correlated traits. We used 172 first-generation descendants of wild-caught mice from the hybrid zone to measure the length of stylopod (humerus / femur), zeugopod (ulna / tibia) and autopod (metacarpal / metatarsal) elements in skeletal CT scans. We find phenotypic covariation between limb elements in the hybrids similar to patterns previously described in M. m. domesticus inbred strains, suggesting that the hybrid genotypes do not influence the covariation pattern in a major way. Mapping was performed using 143,592 SNPs and identified several genomic regions associated with length differences in each bone. Each candidate region explains only a small proportion of phenotypic variance, suggesting that bone length is highly polygenic. None of the candidate regions includes the canonical genes known to control embryonic limb development. Instead, we are able to identify candidate genes with known roles in osteoblast differentiation and bone structure determination, as well as recently evolved genes of, as yet, unknown function.两种家鼠亚种——小家鼠（Mus musculus domesticus）与小家鼠（Mus musculus musculus）在欧洲形成一条狭窄的杂交带。杂交带内的小鼠呈现高度遗传混合，涵盖了两个亚种间所有程度的混合祖先谱系。鉴于这两个亚种形态特征差异显著，因此这些自然杂交种可用于高分辨率全基因组关联定位，以直接推断候选基因。本研究聚焦于肢骨长度差异，该性状对于理解发育相关性状的演化具有重要研究价值。我们使用了172只来自该杂交带的野生小鼠的第一代后代，通过骨骼CT扫描测量了近肢节（stylopod，肱骨/股骨）、中肢节（zeugopod，尺骨/胫骨）以及远肢节（autopod，掌骨/跖骨）的长度。研究发现，杂交小鼠的肢体骨骼间的表型协变模式与此前在小家鼠近交系中报道的模式相似，表明杂交基因型不会对该协变模式产生显著影响。本研究采用143592个单核苷酸多态性（Single Nucleotide Polymorphism, SNP）进行关联定位，在每块骨骼中鉴定出多个与长度差异相关的基因组区域。每个候选区域仅能解释少量表型方差，提示肢骨长度属于高度多基因调控的性状。所有候选区域均未包含已知调控胚胎肢体发育的经典基因。相反，我们成功鉴定出一批候选基因，这些基因已知在成骨细胞分化和骨骼结构决定中发挥作用，同时还发现了一批近期演化而来、功能尚不明晰的基因。