A phylogenetic approach uncovers cryptic endogenous retrovirus subfamilies in the primate lineage.

Authors

Xun Chen, Zicong Zhang, Yizhi Yan, Clement Goubert, Guillaume Bourque, Fumitaka Inoue

Published in

Science advances. Volume 11. Issue 29. Pages eads9164. Jul 18, 2025. Epub Jul 18, 2025.

Abstract

Current approaches for classifying and annotating endogenous retroviruses (ERVs) and their long terminal repeats (LTRs) have limited resolution and are inaccurate. Here, we developed an annotation approach based on phylogenetic analysis and cross-species conservation. Focusing on the evolutionarily young LTR subfamilies known as MER11A/B/C, we revealed the presence of four "new subfamilies," suggesting a new annotation for 412 (19.8%) of these repeat elements. We then validated their regulatory potential using a massively parallel reporter assay. We further identified motifs associated with their differential activities including an ape-specific gain of SOX-related motifs through a single-nucleotide deletion. By applying our approach across 53 simian-enriched LTR subfamilies, we defined 75 new subfamilies and found a novel annotation for a total of 3807 (30.0%) instances from 26 subfamilies. With this refined annotation of simian-enriched LTRs, it will be possible to better understand the evolution in primate genomes and potentially identify critical roles for ERVs and their LTRs in the hosts.

PMID:
40680142
Bibliographic data and abstract were imported from PubMed on 19 Jul 2025.

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