The mole genome reveals regulatory rearrangements associated with adaptive intersexuality.

Abstract

Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, <i>Talpa occidentalis</i>, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving <i>CYP17A1</i>, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor gene <i>FGF9</i>, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole <i>CYP17A1</i> enhancer or overexpressing <i>FGF9</i> showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.