CENP-A and centromere evolution in equids.
Abstract: While the centromeric function is conserved and epigenetically specified by CENP-A, centromeric DNA, typically composed of satellite repeats, is highly divergent and rapidly evolving. In the species of the genus Equus (horses, asses and zebras), also known as equids, the numerous centromeres devoid of satellite repeats enabled us to carry out molecular analysis of centromeric chromatin establishing a unique model system for mammalian centromere biology. In this review, after a brief description of the rapid evolution of equids, we outline one of our most relevant initial discoveries: the position of CENP-A binding domains is variable among individuals giving rise to epialleles which are inherited as Mendelian traits. This positional variability was recently confirmed in human centromeres whose repetitive DNA organization could be analyzed thanks to telomere-to-telomere (T2T) genome assemblies. Another unexpected observation was that, in equids, CENP-B does not bind the centromeric core and is uncoupled from CENP-A and CENP-C. CENP-B is absent from the majority of chromosomes while the CENP-B binding DNA sequence (CENP-B box) is comprised within a satellite that is localized at pericentromeric or terminal positions. Finally, comparative molecular and cytogenetic analyses of satellite-free centromeres revealed that the birth of neocentromeres during the evolution of this genus occurred through two alternative mechanisms: centromere repositioning and Robertsonian fusion. These events played a key role in karyotype reshuffling and speciation. Investigating centromere organization in equids provided new insights into the complexity of centromere organization across the vast biodiversity of the mammalian world, where the majority of species remain understudied.
© 2025. The Author(s).
Publication Date: 2025-06-30 PubMed ID: 40586953PubMed Central: PMC12208984DOI: 10.1007/s10577-025-09773-3Google Scholar: Lookup
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Summary
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The research article is a molecular review focused on centromeres, specifically their diversity and rapid evolution in different species of the Equus genus (horses, asses, and zebras). The study highlights key discoveries about the positional variability of CENP-A binding domains and their inheritance as Mendelian traits, and CENP-B’s uncoupling from CENP-A and CENP-C.
Centromeres and the Equus Genus
- The study focuses on the varied and rapidly evolving centromeric DNA in the species from the Equus genus. These species have numerous centromeres devoid of satellite repeats which allowed for an in-depth molecular analysis.
- On top of studying the rapid evolution of equids, the researchers also established these animals as a unique model system for the study of mammalian centromere biology.
The Positional Variability of CENP-A Binding Domains
- One significant finding from the research is the discovery that the position of CENP-A binding domains can vary among individuals.
- This variation results in different epialleles being created, and these are inherited as Mendelian traits (traits that follow specific patterns of inheritance).
- Recent research in human centromeres confirmed this variability, thanks to ‘telomere-to-telomere’ genome assemblies that allowed the analysis of repetitive DNA organization.
CENP-B’s Uncoupling from CENP-A and CENP-C
- The research also uncovered a surprise in equid centromeres: CENP-B doesn’t bind to the centromeric core and is instead uncoupled from CENP-A and CENP-C.
- Most chromosomes are missing CENP-B, while the DNA sequence it can bind to (the CENP-B box) is found inside a satellite at pericentromeric or terminal positions.
Neocentromeres and Karyotype Reshuffling
- Finally, when conducting a comparative molecular and cytogenetic analysis of satellite-free centromeres, they found two alternative mechanisms that created neocentromeres (new centromeres): centromere repositioning and Robertsonian fusion.
- These events played a crucial role in the reshuffling of karyotypes (the number and visual appearance of chromosomes in the cell nuclei) and speciation.
Implications and Conclusion
- This research adds valuable information to our understanding of centromere organization in equids, which may have wider implications for the study of diverse mammals, as many species remain understudied.
- This research gains importance given that centromeres play a crucial role in cell division, therefore understanding their organization and functioning could have significant implications for understanding species evolution and potentially tackling diseases related to cell division.
Cite This Article
APA
(2025).
CENP-A and centromere evolution in equids.
Chromosome Res, 33(1), 13.
https://doi.org/10.1007/s10577-025-09773-3 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Centromere / genetics
- Centromere / metabolism
- Centromere Protein A / genetics
- Equidae / genetics
- Evolution, Molecular
- DNA, Satellite / genetics
- Humans
- Horses / genetics
- Chromosomal Proteins, Non-Histone / genetics
- Chromosomal Proteins, Non-Histone / metabolism
- Centromere Protein B / genetics
Grant Funding
- 2019-67015-29340/Project Accession 1018854 / National Institute of Food and Agriculture
- 2019-67015-29340/Project Accession 1018854 / National Institute of Food and Agriculture
- 2019-67015-29340/Project Accession 1018854 / National Institute of Food and Agriculture
- 2019-67015-29340/Project Accession 1018854 / National Institute of Food and Agriculture
- 2019-67015-29340/Project Accession 1018854 / National Institute of Food and Agriculture
- 2019-67015-29340/Project Accession 1018854 / National Institute of Food and Agriculture
- 2019-67015-29340/Project Accession 1018854 / National Institute of Food and Agriculture
- 2019-67015-29340/Project Accession 1018854 / National Institute of Food and Agriculture
- 2019-67015-29340/Project Accession 1018854 / National Institute of Food and Agriculture
Conflict of Interest Statement
Declarations. Ethics approval: Not applicable. Consent to publish: Not applicable. Competing interests: The authors declare no competing interests.
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