Saltations of c is-regulatory modules in Canidae and Hominidae

Abstract Dogs, which were segregated from wolves about thirty thousand years ago, show unique human-similar social-cognitive abilities. However, the genomic basis accounting for the phenotypic saltation between dog and wolf remains unclear. We performed a comparative analysis of genome-wide cis-regu...

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Main Authors: Jianhui Shi, Linting Wang, Lei M. Li
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-13034-y
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author Jianhui Shi
Linting Wang
Lei M. Li
author_facet Jianhui Shi
Linting Wang
Lei M. Li
author_sort Jianhui Shi
collection DOAJ
description Abstract Dogs, which were segregated from wolves about thirty thousand years ago, show unique human-similar social-cognitive abilities. However, the genomic basis accounting for the phenotypic saltation between dog and wolf remains unclear. We performed a comparative analysis of genome-wide cis-regulatory element frequencies (CREF) for five canids: dog, dingo, red fox, dhole, and wolf, along with four hominids. For each species, genome-wide CREFs are organized into a matrix. The species-specific CREF matrix is stratified into multiple dual eigen-modules through robust singular value decomposition. Cross-species comparisons of dual eigen-modules demonstrated that the top three eigen-modules are highly conserved while the fourth and fifth ones underwent a saltation in dogs. The red fox is closest to the degenerate point characterizing the onset of saltation. Gene enrichment analysis and motif analysis revealed that myelination, long-term memory, and cochlear development are significantly enhanced at level four in both humans and dogs, but not in wolves. Cross-family comparisons revealed a more similar cognition-memory module between humans and dogs than between humans and chimpanzees. Not only the presence of cis-elements but also their frequencies are crucial for deciphering the regulatory saltations that characterize a striking convergent evolution of dogs and humans in proximal regulatory sequences.
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spelling doaj-art-e6f93c3fffda4cebb6ea9510d09887d92025-08-20T03:46:01ZengNature PortfolioScientific Reports2045-23222025-08-0115112010.1038/s41598-025-13034-ySaltations of c is-regulatory modules in Canidae and HominidaeJianhui Shi0Linting Wang1Lei M. Li2State Key Laboratory of Mathematical Science, Academy of Mathematics and Systems Science, Chinese Academy of SciencesState Key Laboratory of Mathematical Science, Academy of Mathematics and Systems Science, Chinese Academy of SciencesState Key Laboratory of Mathematical Science, Academy of Mathematics and Systems Science, Chinese Academy of SciencesAbstract Dogs, which were segregated from wolves about thirty thousand years ago, show unique human-similar social-cognitive abilities. However, the genomic basis accounting for the phenotypic saltation between dog and wolf remains unclear. We performed a comparative analysis of genome-wide cis-regulatory element frequencies (CREF) for five canids: dog, dingo, red fox, dhole, and wolf, along with four hominids. For each species, genome-wide CREFs are organized into a matrix. The species-specific CREF matrix is stratified into multiple dual eigen-modules through robust singular value decomposition. Cross-species comparisons of dual eigen-modules demonstrated that the top three eigen-modules are highly conserved while the fourth and fifth ones underwent a saltation in dogs. The red fox is closest to the degenerate point characterizing the onset of saltation. Gene enrichment analysis and motif analysis revealed that myelination, long-term memory, and cochlear development are significantly enhanced at level four in both humans and dogs, but not in wolves. Cross-family comparisons revealed a more similar cognition-memory module between humans and dogs than between humans and chimpanzees. Not only the presence of cis-elements but also their frequencies are crucial for deciphering the regulatory saltations that characterize a striking convergent evolution of dogs and humans in proximal regulatory sequences.https://doi.org/10.1038/s41598-025-13034-yCis-regulatory moduleSaltationCan-SINE elementCognitionEmergenceSingular value decomposition
spellingShingle Jianhui Shi
Linting Wang
Lei M. Li
Saltations of c is-regulatory modules in Canidae and Hominidae
Scientific Reports
Cis-regulatory module
Saltation
Can-SINE element
Cognition
Emergence
Singular value decomposition
title Saltations of c is-regulatory modules in Canidae and Hominidae
title_full Saltations of c is-regulatory modules in Canidae and Hominidae
title_fullStr Saltations of c is-regulatory modules in Canidae and Hominidae
title_full_unstemmed Saltations of c is-regulatory modules in Canidae and Hominidae
title_short Saltations of c is-regulatory modules in Canidae and Hominidae
title_sort saltations of c is regulatory modules in canidae and hominidae
topic Cis-regulatory module
Saltation
Can-SINE element
Cognition
Emergence
Singular value decomposition
url https://doi.org/10.1038/s41598-025-13034-y
work_keys_str_mv AT jianhuishi saltationsofcisregulatorymodulesincanidaeandhominidae
AT lintingwang saltationsofcisregulatorymodulesincanidaeandhominidae
AT leimli saltationsofcisregulatorymodulesincanidaeandhominidae