Dynamics of gene conversion in human MSY palindromes

The Male Specific region of the human Y chromosome (MSY) is characterized by the presence of 8 near identical 'pseudo-diploid' sequences, called palindromes, which are designated as P1–P8. Palindromes are composed of inverted repeats (palindrome arms), separated by a non-duplicated spacer. Although these structures originated in a non-recombining context, they show evidence of a strong recombinational activity. Palindromes exhibit more than 99.94% sequence identity between arms, due to the homogenizing effect of arm-to-arm gene conversion (GC), a type of recombination which involves the non-reciprocal transfer of genetic information from a “donor” sequence to a highly similar “acceptor” sequence. The independent appearance of these paralogue structures in sex chromosomes of many different species suggests that they may have an important biological meaning. It has been hypothesized that the palindromic organization and the establishment of inter-paralogs gene conversion have a strong adaptive significance since the arm-to-arm GC may allow double-strand break repair and the efficient removal of deleterious mutations. Thus, it has been proposed that this mechanism was acquired to maintain the structural integrity of multi-copy genes involved in the male-fertility. Moreover, it has been hypothesized that gene conversion evolved as a mechanism to retain the ancestral state of sequences: a de novo mutation in a palindrome arm is preferentially back mutated to the ancestral state rather than transmitted to the other arm. In this contest, to gain new insights into the dynamics of gene conversion within human Y chromosome palindromes, we performed next-generation sequencing (depth >50×) of 3 palindromes (P6, P7 and P8) in 157 samples, chosen to represent the most divergent evolutionary lineages of the MSY. In this analysis, we overcame the problem of the inaccurate mapping of the duplicated reads, and we performed a sequencing depth analysis to detect deletions or duplications which may result in genotype miscalling. We identified more than 200 paralogue sequence variants and 140 GC events. Mapping these GC events across a stable and non-ambiguous Y chromosome phylogeny enabled the calculation of a precise Y-Y gene conversion rate for each palindrome and the assessment of the direction of the recombinational activity. From these analyses we conclude that MSY palindromes have an evolutionary pattern more complex than previously thought.