Apparent intrachromosomal exchange on the human Y chromosome explained by population history

The human Y chromosome displays an unusual content of repetitive sequences. Y-chromosomal repeats are potential targets for intrachromosomal recombination, which is thought to be involved in a number of Y-associated defects, such as male infertility. Such rearrangements could potentially be investigated by the use of highly polymorphic DNA markers located within the repeat units, such as microsatellites. Here we analyse the two copies of the Y-chromosomal microsatellite DYS385, which we identified and localized to an ∼ 190 kb duplicated and inverted fragment at Yq11.223. We found a highly significant correlation (r=0.853, P<0.001) and a nonsignificant difference in a χ²-test (χ² = 15.45, P>0.05) between the allele frequency distributions at both copies of the Y-STR in a German population sample (n = 70). Such nearly identical allele frequency distribution between two copies of a duplicated highly polymorphic microsatellite cannot be explained by the independent mutational process that creates microsatellite alleles. Instead, this might be interpreted as evidence for a reciprocal intrachromosomal exchange process between the duplicated fragments. However, more detailed analyses using additional human populations as well as additional Y chromosome markers revealed that this phenomenon is highly population-specific and disappears completely when Y-STR diversity is analysed in association with two Y-SNP haplogroups. We found that the diversity of the two DYS385 loci (and other Y-STRs) is highly depending on the haplogroup background, and that equal proportions of both haplogroups in the German sample explains the nearly identical allele frequency distributions at the two DYS385 loci. Thus, we demonstrate here that allele frequency distributions at duplicate loci that are suggestive of intrachromosomal recombination can be explained solely by population history.