Meiotic recombination is an important driver of sequence evolution at hotspots
Sprache des Vortragstitels:
Englisch
Original Tagungtitel:
American Society of Human Genetics
Sprache des Tagungstitel:
Englisch
Original Kurzfassung:
Meiotic recombination, a key biological process during germ cell production, is clustered in recombination hotspots that undergo rapid sequence degeneration, as shown repeatedly by population data analysis. The exact mechanisms driving this sequence evolution are still not well known. By sequencing a large number of single recombinants obtained from human sperm, we have shown that recombination is mutagenic and crossovers are enriched for de novo CG to TA transitions, especially at methylated CpG sites, which could be the predominant mutational pattern in processes involving single stranded DNA. Another mechanism driving the sequence evolution at hotspots is biased gene conversion. Our large data set also provided new evidence that the transmission of GC-alleles is favored during crossing-over and showed that GC biased gene conversion (gBGC) is a strong driver of hotspot sequence evolution opposing mutation. We have also examined the evolution of short tandem repeats (STR) at hotspots by analyzing the transmission of polymorphic STRs and their effect on recombination. We observed that a long polymorphic tract of polyAs (A9/A19) located at the center of the hotspot can shift the hotspot center and reduce the overall crossover frequency. In addition, the transmission of STRs do not follow the Mendelian rules of segregation (50:50), but longer repeats are transmitted more frequently than shorter ones, and our data show for the first time with experimental evidence an insertion-biased gene conversion (iBGC) in a STR (A6/A7) within a hotspot. The molecular mechanisms inducing the observed patterns are not clear yet; however, the recurrent repair of double-strand breaks (DSB), required for the initiation of recombination, seems to play an important role.
Sprache der Kurzfassung:
Englisch
Englischer Vortragstitel:
Meiotic recombination is an important driver of sequence evolution at hotspots