Genetic diversity at three palindromic sequences of the human Y chromosome

One of the most striking structural features of the male specific region of the human Y chromosome (MSY) is the presence, within the ampliconic sequences, of eight massive palindromes (P1-P8). Each palindrome is composed of two large inverted repeats (arms) separated by a small “spacer” sequence at the centre. These elements, ranging from 30 kb to 2.9 Mb, contain many testis-specific genes and typically exhibit > 99.9% intra-palindromic (arm-to-arm) sequence identity. It has been hypothesized that the high observed sequence similarity is due to abundant gene conversion events between the arms of each palindrome. Although the occurrence of arm-to-arm gene conversion has been clearly demonstrated, the effect of this molecular mechanism on the genetic diversity of palindromes, as well as its rate and extension, remain largely unexplored. To gain new insights into the evolutionary history of the human Y chromosome palindromic sequences and to shed light into the dynamics of intra-palindrome gene conversion, we analysed by high-coverage next- generation sequencing (50x) the shortest known palindromes (P6, P7 and P8) and their relative spacers (for a total of about 0.3 Mb) in 158 samples chosen to represent most of the independent evolutionary lineages (haplogroups) of the MSY. By this analysis we identified several gene conversion events and a peculiar mutational pattern of the palindrome arms with respect to the spacer. Moreover, we found few phylogenetically conserved paralogous sequence variants (PSVs), suggestive of a high arm-to-arm gene conversion activity. Because Y chromosomes are clonally inherited from father to son, it has been possible to capture their evolutionary relationships in a robust phylogenetic tree with known age of each node. By mapping gene conversion events across a Y tree based on thousands of stable mutations obtained from 3.3 Mb of single copy MSY sequences, we were able to calculate a precise Y-Y gene conversion rate for each of the palindromes here analysed.