CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres

Abstract

Background While CENP-A is the epigenetic determinant of the centromeric function, the role of CENP-B, the sole centromeric protein binding a specific DNA sequence (CENP-B-box), remains elusive. In the few mammalian species analyzed so far, the CENP-B box is contained in the major satellite repeat that is present at all centromeres. We previously demonstrated that, in the genus Equus, whose species underwent rapid and recent evolution, numerous centromeres lack any satellite repeat. Results In four Equus species, CENP-B is expressed but does not bind the satellite-free and the majority of satellite-based centromeres while it is localized at several ancestral now inactive centromeres. Centromeres lacking CENP-B are functional and recruit normal amounts of CENP-A and CENP-C. The absence of CENP-B is related to the lack of CENP-B boxes rather than to peculiar features of the protein itself. CENP-B boxes are comprised in a previously undescribed repeat which is not the major satellite bound by CENP-A. Comparative sequence analysis suggested that this satellite was centromeric in the equid ancestor, lost centromeric function during evolution and gave rise to a shorter CENP-A bound repeat not containing the CENP-B box but being enriched in dyad symmetries. Conclusions We propose that the uncoupling between CENP-B and CENP-A may have played a role in the extensive evolutionary reshuffling of equid centromeres. This study provides new insights into the complexity of centromere organization in a largely biodiverse world where the majority of mammalian species still have to be studied.