Recombination regulator PRDM9 influences the instability of its own coding sequence in humans.
Proc Natl Acad Sci U S A
; 110(2): 600-5, 2013 Jan 08.
Article
em En
| MEDLINE
| ID: mdl-23267059
ABSTRACT
PRDM9 plays a key role in specifying meiotic recombination hotspot locations in humans and mice via recognition of hotspot sequence motifs by a variable tandem-repeat zinc finger domain in the protein. We now explore germ-line instability of this domain in humans. We show that repeat turnover is driven by mitotic and meiotic mutation pathways, the latter frequently resulting in substantial remodeling of zinc fingers. Turnover dynamics predict frequent allele switches in populations with correspondingly fast changes of the recombination landscape, fully consistent with the known rapid evolution of hotspot locations. We found variation in meiotic instability between men that correlated with PRDM9 status. One particular "destabilizer" variant caused hyperinstability not only of itself but also of otherwise-stable alleles in heterozygotes. PRDM9 protein thus appears to regulate the instability of its own coding sequence. However, destabilizer variants are strongly self-limiting in populations and probably have little impact on the evolution of the recombination landscape.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Recombinação Genética
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Histona-Lisina N-Metiltransferase
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Evolução Molecular
/
Sequência de DNA Instável
Tipo de estudo:
Prognostic_studies
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article