Andrea J Betancourt, Thomas Ebner, Irene Tiemann-Boege, Barbara Arbeithuber,
"Crossovers are associated with mutation and biased gene conversion at recombination hotspots"
, in Proceedings of the National Academy of Sciences of the United States of America (PNAS), Vol. 15, Nummer 1, Seite(n) 759-63, 2-2015, ISSN: 1091-6490
Original Titel:
Crossovers are associated with mutation and biased gene conversion at recombination hotspots
Sprache des Titels:
Englisch
Original Kurzfassung:
Meiosis is a potentially important source of germline mutations, as
sites of meiotic recombination experience recurrent double-strand
breaks (DSBs). However, evidence for a local mutagenic effect of
recombination from population sequence data has been equivocal,
likely because mutation is only one of several forces shaping
sequence variation. By sequencing large numbers of single
crossover molecules obtained from human sperm for two recombination
hotspots, we find direct evidence that recombination
is mutagenic: Crossovers carry more de novo mutations than
nonrecombinant DNA molecules analyzed for the same donors
and hotspots. The observed mutations were primarily CG to TA
transitions, with a higher frequency of transitions at CpG than
non-CpGs sites. This enrichment of mutations at CpG sites at
hotspots could predominate in methylated regions involving
frequent single-stranded DNA processing as part of DSB repair.
In addition, our data set provides evidence that GC alleles are
preferentially transmitted during crossing over, opposing mutation,
and shows that GC-biased gene conversion (gBGC) predominates
over mutation in the sequence evolution of hotspots. These
findings are consistent with the idea that gBGC could be an
adaptation to counteract the mutational load of recombination.
Sprache der Kurzfassung:
Englisch
Journal:
Proceedings of the National Academy of Sciences of the United States of America (PNAS)
Forschungs-