Genomic insights into adaptation to bipedal saltation and desert-like habitats of jerboas

Jerboas is a lineage of small rodents displaying atypical mouse-like morphology with elongated strong hindlimbs and short forelimbs. They have evolved obligate bipedal saltation and acute senses, and been well-adapted to vast desert-like habitats. Using a newly sequenced chromosome-scale genome of the Mongolian five-toed jerboa (Orientallactaga sibirica), our comparative genomic analyses and in vitro functional assays showed that the genetic innovations in both protein-coding and non-coding regions played an important role in jerboa morphological and physiological adaptation. Jerboa-specific amino acid substitutions, and segment insertions/deletions (indels) in conserved non-coding elements (CNEs) were found in components of proteoglycan biosynthesis pathway (XYLT1 and CHSY1), which plays an important role in limb development. Meanwhile, we found specific evolutionary changes functionally associated with energy or water metabolism (e.g., specific amino acid substitutions in ND5 and indels in CNEs physically near ROR2) and senses (e.g., expansion of vomeronasal receptors and the FAM136A gene family) in jerboas. Further dual-luciferase reporter assay verified that some of the CNEs with jerboa-specific segment indels exerted a significantly different influence on luciferase activity, suggesting changes in their regulatory function in jerboas. Our results revealed the potential molecular mechanisms underlying jerboa adaptation since the divergence from the Eocene-Oligocene transition, and provided more resources and new insights to enhance our understanding of the molecular basis underlying the phenotypic diversity and the environmental adaptation of mammals.