Molecular conflicts disrupting centromere maintenance contribute to Xenopus hybrid inviability.

Autor:	Kitaoka M; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA., Smith OK; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA., Straight AF; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA., Heald R; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA. Electronic address: bheald@berkeley.edu.
Jazyk:	angličtina
Zdroj:	Current biology : CB [Curr Biol] 2022 Sep 26; Vol. 32 (18), pp. 3939-3951.e6. Date of Electronic Publication: 2022 Aug 15.
DOI:	10.1016/j.cub.2022.07.037
Abstrakt:	Although central to evolution, the causes of hybrid inviability that drive reproductive isolation are poorly understood. Embryonic lethality occurs when the eggs of the frog X. tropicalis are fertilized with either X. laevis or X. borealis sperm. We observed that distinct subsets of paternal chromosomes failed to assemble functional centromeres, causing their mis-segregation during embryonic cell divisions. Core centromere DNA sequence analysis revealed little conservation among the three species, indicating that epigenetic mechanisms that normally operate to maintain centromere integrity are disrupted on specific paternal chromosomes in hybrids. In vitro reactions combining X. tropicalis egg extract with either X. laevis or X. borealis sperm chromosomes revealed that paternally matched or overexpressed centromeric histone CENP-A and its chaperone HJURP could rescue centromere assembly on affected chromosomes in interphase nuclei. However, although the X. laevis chromosomes maintained centromeric CENP-A in metaphase, X. borealis chromosomes did not and also displayed ultra-thin regions containing ribosomal DNA. Both centromere assembly and morphology of X. borealis mitotic chromosomes could be rescued by inhibiting RNA polymerase I or preventing the collapse of stalled DNA replication forks. These results indicate that specific paternal centromeres are inactivated in hybrids due to the disruption of associated chromatin regions that interfere with CENP-A incorporation, at least in some cases due to conflicts between replication and transcription machineries. Thus, our findings highlight the dynamic nature of centromere maintenance and its susceptibility to disruption in vertebrate interspecies hybrids. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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