CENP‑A and Centromere Evolution in Equids

Authors

Eleonora Cappelletti, University of Pavia, ItalyFollow
Francesca M. Piras, San Matteo Hospital Foundation, Pavia, Italy
Marialaura Biundo, University of Pavia, Italy
Rebecca R. Bellone, University of California, Davis
Carrie J. Finno, University of California, Davis
Ted S. Kalbfleisch, University of Kentucky
Jessica L. Petersen, University of Nebraska-Lincoln
Solomon G. Nergadze, University of Pavia, Italy
Elena Giulotto, University of Pavia, ItalyFollow

ORCID IDs

Piras https://orcid.org/0000-0002-7418-3976

Biundo https://orcid.org/0009-0003-5975-8369

Finno https://orcid.org/0000-0001-5924-0234

Nergadze https://orcid.org/0000-0001-8121-0189

Document Type

Article

Date of this Version

2025

Citation

Chromosome Research (2025) 33: 13

doi: 10.1007/s10577-025-09773-3

Comments

Open access

License: CC BY-NC-ND 4.0

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.