期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：9
DOI：10.1073/pnas.2114401119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
We take a phylogenetic approach to search for molecular partners of PRDM9, a key meiotic recombination gene, by leveraging the fact that the complete
PRDM9 gene has been lost at least 13 times independently in vertebrates. We identify two genes,
ZCWPW1 and its paralog
ZCWPW2, whose presence or absence across vertebrates is coupled to that of
PRDM9. ZCWPW1 was recently shown to be recruited to sites of PRDM9 binding and to aid in the repair of double strand breaks. ZCWPW2 is likely recruited to sites of PRDM9 binding as well; its tight coevolution with
PRDM9 across vertebrates suggests that it too plays an important role in mammals and beyond, either in double strand break formation or repair.
In most mammals and likely throughout vertebrates, the gene
PRDM9 specifies the locations of meiotic double strand breaks; in mice and humans at least, it also aids in their repair. For both roles, many of the molecular partners remain unknown. Here, we take a phylogenetic approach to identify genes that may be interacting with PRDM9 by leveraging the fact that
PRDM9 arose before the origin of vertebrates but was lost many times, either partially or entirely—and with it, its role in recombination. As a first step, we characterize PRDM9 domain composition across 446 vertebrate species, inferring at least 13 independent losses. We then use the interdigitation of
PRDM9 orthologs across vertebrates to test whether it coevolved with any of 241 candidate genes coexpressed with PRDM9 in mice or associated with recombination phenotypes in mammals. Accounting for the phylogenetic relationship among a subsample of 189 species, we find two genes whose presence and absence is unexpectedly coincident with that of
PRDM9:
ZCWPW1, which was recently shown to facilitate double strand break repair, and its paralog
ZCWPW2, as well as, more tentatively,
TEX15 and
FBXO47.
ZCWPW2 is expected to be recruited to sites of PRDM9 binding; its tight coevolution with
PRDM9 across vertebrates suggests that it is a key interactor within mammals and beyond, with a role either in recruiting the recombination machinery or in double strand break repair.
