Abstract
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.
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Acknowledgements
We thank the following companies and individuals for their contributions to this study: Cyagen Biosciences Inc. and Shanghai Biomodel Organism Science & Technology Development Co., Ltd for generating mice; Jianping Ding, Chunxiao Zhang, Wenshuai Wang, Ya Zhao, Ligang Wu, Fangzhi Tan, Yunbo Qiao, and Jiayue Liu for technical supports; Patricia Guijarro Larraz for providing the mCherry template; Zhong-Hui Weng, Yun Qian, Fang Yu, and the animal caretaker team for assistance with animal care and experiments; Chao-Hung Lee, Ya-Ping Zhang, Cemalettin Bekpen, Diethard Tautz and Shi-Qing Cai for providing valuable advices. This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13040800), the National Natural Science Foundation of China (91731304, 91531306, 31771180, and 91732106), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05).
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Y.W., G.D., Z.G., G.L., K.T., Z.S., G.W. and H.L. developed the concepts. Y.W., G.D., Z.G., G.L., K.T., Chun X., N.J. and H.L. developed the methods. H.L. programmed the software. Y.W., G.D., Z.G., G.L., H.S., Q.L., Chuan X., Y.M., Y.E.Z., P.K., Y.W. and H.L. analyzed the data. Y.W., G.D., Z.G., G.L., Y.C., H.C., S.F., S.Q., X.L., N.W. and H.L. carried out the investigation. Q.L. provided the resources. Y.W., G.D., Z.G., G.L., Y.P., Chun X. and H.L. wrote the original manuscript. Y.W., G.D., Z.G., G.L., K.T., J.H., Z.S., G.W., Y.P. and H.L. reviewed and edited the manuscript. H.L. supervised the study and acquired the funding.
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Wang, Y., Dai, G., Gu, Z. et al. Accelerated evolution of an Lhx2 enhancer shapes mammalian social hierarchies. Cell Res 30, 408–420 (2020). https://doi.org/10.1038/s41422-020-0308-7
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DOI: https://doi.org/10.1038/s41422-020-0308-7
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