Deciphering the role of rapidly evolving conserved elements in primate brain development and exploring their potential involvement in Alzheimer's Disease

Hu, Benxia, Zhuang, Xiao-Lin, Zhou, Long, Zhang, Guojie, Cooper, David N. ORCID: https://orcid.org/0000-0002-8943-8484 and Wu, Dong-Dong 2024. Deciphering the role of rapidly evolving conserved elements in primate brain development and exploring their potential involvement in Alzheimer's Disease. Molecular Biology and Evolution 41 (1) , msae001. 10.1093/molbev/msae001

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Abstract

Although previous studies have identified human-specific accelerated regions as playing a key role in the recent evolution of the human brain, the characteristics and cellular functions of rapidly evolving conserved elements (RECEs) in ancestral primate lineages remain largely unexplored. Here, based on large-scale primate genome assemblies, we identify 888 RECEs that have been highly conserved in primates that exhibit significantly accelerated substitution rates in the ancestor of the Simiiformes. This primate lineage exhibits remarkable morphological innovations, including an expanded brain mass. Integrative multiomic analyses reveal that RECEs harbor sequences with potential cis-regulatory functions that are activated in the adult human brain. Importantly, genes linked to RECEs exhibit pronounced expression trajectories in the adult brain relative to the fetal stage. Furthermore, we observed an increase in the chromatin accessibility of RECEs in oligodendrocytes from individuals with Alzheimer's disease (AD) compared to that of a control group, indicating that these RECEs may contribute to brain aging and AD. Our findings serve to expand our knowledge of the genetic underpinnings of brain function during primate evolution.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: cc-by
Publisher:	Oxford University Press
ISSN:	0737-4038
Date of First Compliant Deposit:	22 January 2024
Date of Acceptance:	29 December 2023
Last Modified:	22 Jan 2024 11:15
URI:	https://orca.cardiff.ac.uk/id/eprint/165713

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