Accelerated evolution of an Lhx2 enhancer shapes mammalian social hierarchies

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2020,（5）
• 页码范围: 408-420
• 页数: 13页
• 语种: 英文

摘要

Social hierarchies emerged during evolution,and social rank influences behavior and health of individuals.However,the evolutionary mechanisms of social hierarchy are still unknown in amniotes.Here we developed a new method and performed a genome-wide screening for identifying regions with accelerated evolution in the ancestral lineage of placental mammals,where mammalian social hierarchies might have initially evolved.Then functional analyses were conducted for the most accelerated region designated as placental-accelerated sequence 1 (PAS1,P=3.15 × 10-18).Multiple pieces of evidence show that PAS1 is an enhancer of the transcription factor gene Lhx2 involved in brain development.PAS1s isolated from various amniotes showed different cis-regulatory activity in vitro,and affected the expression of Lhx2 differently in the nervous system of mouse embryos.PAS1 knock-out mice lack social stratification.PAS1 knock-in mouse models demonstrate that PAS1s determine the social dominance and subordinate of adult mice,and that social ranks could even be turned over by mutated PAS1.All homozygous mutant mice had normal huddled sleeping behavior,motor coordination and strength.Therefore,PAS1-Lhx2 modulates social hierarchies and is essential for establishing social stratification in amniotes,and positive Darwinian selection on PAS1 plays pivotal roles in the occurrence of mammalian social hierarchies.