Mean gene conversion tract length in humans estimated to be 459 bp from UK Biobank sequence data

Abstract

Non-crossover gene conversion is a type of meiotic recombination characterized by the non-reciprocal transfer of genetic material between homologous chromosomes. Gene conversions are thought to occur within relatively short tracts of DNA. However, the number of observable gene conversion tracts per study has so far been limited by the use of pedigree or sperm-typing data to detect gene conversion events. In this study, we propose a statistical method to model the length distribution of gene conversion tracts in humans, using nearly one million gene conversion tracts detected from the UK Biobank whole autosome data. To handle the large number of tracts, we designed a computationally efficient inferential framework. Our method further accounts for regional variation in marker density and heterozygosity across the genome, which can influence the observed length of gene conversion tracts. We allow for multiple candidate tract length distributions and select the best fitting distribution using the Akaike Information Criterion (AIC). Applying our method, we estimate that most tracts have a mean of 16.9 bp (95% CI: [16.4, 17.0]), and only a very small proportion of tracts have a much larger mean of 724.7 bp (95% CI: [720.1, 728.7]). We further estimate the proportion of gene conversion tracts with the larger mean to be 0.00525 (95% CI: [0.005, 0.00525]). After stratifying by crossover-hotspot overlap, we infer that tracts whose midpoints lie within crossover hotspots are, on average, longer than the remaining tracts.