2011bowdengrphd.pdf (4.82 MB)
Gene conversion on the human Y chromosome
thesisposted on 2011-05-13, 12:38 authored by Georgina Rebecca Bowden
For many years it was believed that recombination on the human Y chromosome was restricted to the XY-homologous pseudoautosomal regions, with over 95% of the Y chromosome believed to be non-recombining. Over the past 7 years gene conversion has been shown to occur between several classes of paralog situated outside of the pseudoautosomal regions. Gene conversion has been shown to occur both intrachromosomally on the Y chromosome, and between the X and the Y chromosomes (Cruciani et al. 2010; Rosser et al. 2009; Rozen et al. 2003; Trombetta et al. 2009) and several biases in the direction of gene conversion have been suggested (Bosch et al. 2004; Rozen et al. 2003; Trombetta et al. 2009). This study has used interspecies sequence comparisons to identify regions of the Y chromosome which are likely to be undergoing gene conversion. Phylogenetic analysis of paralogous sequence variants (PSVs) or gametologous sequence variants (GSVs) identified between these regions has been carried out. Significantly lower interspecies divergence was observed between orthologous palindrome arms in comparison to the non-duplicated spacers (P=0.0001, 2-tailed Fisher exact test) suggesting that conservative gene conversion occurs between the arms of palindromes. Significant evidence (P=0.0001, chi square test) of conservative gene conversion was observed between the arms of P6 with genotyping of 10 PSVs identifying 62 conversion events, of which 52 convert to the ancestral allele and 10 to the derived allele. Evidence of gene conversion was observed between the VCX/VCY and TGIF2LX/Y genes and between IR1 and P1. This study suggests that gene conversion between Y chromosome paralogs is conservative of the ancestral sequence via an unknown mechanism and that conservative gene conversion is not limited to genic regions of the Y chromosome. It also demonstrates that gene conversion can occur between multiple Yq paralogs and multiple XY-homologous genes.
Date of award2011-04-01
Awarding institutionUniversity of Leicester