This study is reported by groups of Guang Yang, Shixia Xu and Qiang Qiu from Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Nanjing Normal University, and Northwestern Polytechnical University. Jerboas is a lineage of small rodents displaying atypical mouse-like morphology with elongated strong hindlimbs and short forelimbs, which has been noticed and recorded in the classic Chinese encyclopedic work of the Brush Talks from Dream Brook as "…但前足才寸许，后足几一尺。行则用后足跳，一跃数尺…" (…forelimbs were about one inch but hindlimbs nearly a foot. They hop on the two hindlimbs to move, as far as a few feet at a time…). The team has recently sequenced and reported the chromosome-scale genome of the Mongolian five-toed jerboa (Orientallactaga sibirica), which spans 2.85 Gb and contains 21,074 annotated protein-coding genes. Subsequently, 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 morphological and physiological adaptations of jerboa.
Proteoglycans (PGs), formed by glycosaminoglycans (GAGs), during endochondral ossification are crucial components for the development of bone. Xylosyltransferase (encoded by XYLT1 and XYLT2) and chondroitin synthases (encoded by CHSY1 and CHSY3) are important in the initiation and elongation processes of GAG chains. The authors found seven fixed amino acid substitutions in total, which underwent radical property changes in jerboa XYLT1 and CHSY1 (Figure 1). Additionally, they identified an 11-bp jerboa-specific segment deletion within a conserved non-coding element (CNE) whose target gene is predicted to be XYLT1. Further luciferase activity assay supported the potential regulatory role in the expression of XYLT1 of this deletion (Figure 2). These findings suggest that the cartilage development and GAG biosynthesis signaling pathway contribute to the unique limb development pattern in jerboas.
Furthermore, natural selection acting on energy metabolism-related genes such as COX6A1, UQCRB, and ND5, along with variations in CNEs which are physically near to them, may contribute to the perception and response to reactive oxygen species (ROS). This, in turn, could help mitigate oxidative stress damage resulting from high metabolic demands during bipedal hopping gait of jerboas. Additionally, the team revealed that following the divergence in the Eocene–Oligocene transition, genetic changes in both the protein-coding and non-coding regions potentially led to the evolution of limbs, energy and water metabolism, and specialized sensory systems of jerboas. The genetic innovations underlying the jerboa adaptation described in this study provide more insights into the environmental adaptation and phenotypic evolution occurring in mammals.
