Genomic signatures of selection in the mound-building mouse Mus spicilegus

Abstract

The steppe mouse Mus spicilegus is distinguished by several unusual phenotypes: animals of this species build complex mounds from brush and dirt, and this behavior as well as the pace of development is regulated by season of birth. The genetic and evolutionary basis of species-defining traits in Mus spicilegus is unknown. To discover genomic clues to the mechanisms at play, we took a molecular-evolution approach. Sequence-based tests of protein-coding exons, and of brain-active cis-regulatory regions, revealed a striking excess of evidence for evolutionary acceleration in the M. spicilegus genome relative to those of closely related species. Transcriptional analyses also revealed unique expression programs in the M. spicilegus brain, which could be traced in part to cis-regulatory sequence variation. Hit loci from our molecular-evolution tests tended to be active in the cerebral cortices and hypothalamus and have annotated functions in neuronal development, neural plasticity, or endocrine signaling. In many cases, their orthologs in other animal systems had been implicated in neoteny/the pace of maturation, unusual building behaviors, and autism. Together, our data indicate that M. spicilegus has undergone divergence in brain-active genes to an extent far more than its relatives. We interpret the affected genes under a model in which they mediate the seasonal capacity by M. spicilegus for protracted maturation and mound-building. Thus our work provides an evolutionary interpretation of, and catalog of candidate determinants for, shifts in motivated behavior and development in this intriguing mouse species.

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• biorxiv v1 2026-08-22 source ↗

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