Anguo Liu1,2,7, Nini Wang1,3,7, Guoxiang Xie1,2,7, Yang Li1,2, Xixi Yan1,2, Xinmei Li1,2, Zhenliang Zhu2,4,5, Zhuohui Li1,2, Jing Yang2,4,5, Fanxin Meng1, Mingle Dou1,2, Weihuang Chen1, Nange Ma1,2, Yu Jiang1,2,6, Yuanpeng Gao2,4,5 and Yu Wang1,2 1Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China; 2Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi 712100, China; 3Faculty of Mathematics and Natural Sciences, University of Cologne, and Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University Hospital Cologne, Cologne 50931, Germany; 4College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; 5Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; 6Center for Functional Genomics, Institute of Future Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China

↵7 These authors contributed equally to this work.

Corresponding authors: wang_yunwafu.edu.cn, gaoyuanpeng1990163.com Abstract

Ultraconserved elements (UCEs) are the most conserved regions among the genomes of evolutionarily distant species and are thought to play critical biological functions. However, some UCEs rapidly evolved in specific lineages, and whether they contributed to adaptive evolution is still controversial. Here, using an increased number of sequenced genomes with high taxonomic coverage, we identified 2191 mammalian UCEs and 5938 avian UCEs from 95 mammal and 94 bird genomes, respectively. Our results show that these UCEs are functionally constrained and that their adjacent genes are prone to widespread expression with low expression diversity across tissues. Functional enrichment of mammalian and avian UCEs shows different trends indicating that UCEs may contribute to adaptive evolution of taxa. Focusing on lineage-specific accelerated evolution, we discover that the proportion of fast-evolving UCEs in nine mammalian and 10 avian test lineages range from 0.19% to 13.2%. Notably, up to 62.1% of fast-evolving UCEs in test lineages are much more likely to result from GC-biased gene conversion (gBGC). A single cervid-specific gBGC region embracing the uc.359 allele significantly alters the expression of Nova1 and other neural-related genes in the rat brain. Combined with the altered regulatory activity of ancient gBGC-induced fast-evolving UCEs in eutherians, our results provide evidence that synergy between gBGC and selection shaped lineage-specific substitution patterns, even in the most constrained regulatory elements. In summary, our results show that gBGC played an important role in facilitating lineage-specific accelerated evolution of UCEs, and further support the idea that a combination of multiple evolutionary forces shapes adaptive evolution.

Received February 8, 2023. Accepted August 23, 2023.