title: Transmission distortion affecting human noncrossover but not crossover recombination: a hidden source of meiotic drive.
abstract: Meiotic recombination ensures the correct segregation of homologous chromosomes during gamete formation and contributes to DNA diversity through both large-scale reciprocal crossovers and very localised gene conversion events, also known as noncrossovers. Considerable progress has been made in understanding factors such as PRDM9 and SNP variants that influence the initiation of recombination at human hotspots but very little is known about factors acting downstream. To address this, we simultaneously analysed both types of recombinant molecule in sperm DNA at six highly active hotspots, and looked for disparity in the transmission of allelic variants indicative of any cis-acting influences. At two of the hotspots we identified a novel form of biased transmission that was exclusive to the noncrossover class of recombinant, and which presumably arises through differences between crossovers and noncrossovers in heteroduplex formation and biased mismatch repair. This form of biased gene conversion is not predicted to influence hotspot activity as previously noted for SNPs that affect recombination initiation, but does constitute a powerful and previously undetected source of recombination-driven meiotic drive that by extrapolation may affect thousands of recombination hotspots throughout the human genome. Intriguingly, at both of the hotspots described here, this drive favours strong (G/C) over weak (A/T) base pairs as might be predicted from the well-established correlations between high GC content and recombination activity in mammalian genomes.
authors: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors: Linda
authors: L
authors: Odenthal-Hesse
authors: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors: Ingrid L
authors: IL
authors: Berg
authors: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors: Amelia
authors: A
authors: Veselis
authors: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors: Alec J
authors: AJ
authors: Jeffreys
authors: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors: Celia A
authors: CA
authors: May
mesh_terms: D000483:Alleles; D000818:Animals; D003434:Crossing Over, Genetic; D015894:Genome, Human; D005854:Germ Cells / Q000254:growth & development; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics*; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D013094:Spermatozoa / Q000254:growth & development* / Q000378:metabolism
chemical_list: D009692:Nucleic Acid Heteroduplexes; D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human