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

Abstract

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 B190 kb duplicated and inverted fragment at Yq11.223. We found a highly significant correlation (r ¼ 0.853, Po0.001) and a nonsignificant difference in a v 2 -test (v 2 ¼ 15.45, P40.05) between the allele frequency distributions at both copies of the Y-STR in a German population sample (n ¼ 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.

Y-chromosome diversity in Sweden – A long-time perspective

“…16 However, in the present study we also typed the Saami and Ö sterbotten samples and separated DYS385 into DYS385a and DYS385b for all 383 chromosomes. This was performed according to Kittler et al,17 with the minor modification that 10 ng template DNA was used.…”

Genetic evidence for the Mongolian ancestry of Kalmyks

“…These loci were amplified in pentaplex and quadruplex PCRs, or alternatively in a single nanoplex PCR, and analyzed on an ABI PRISM 377 DNA sequencer (Applied Biosystems), as described elsewhere . In order to distinguish genotypes at the duplicated DYS385a and DYS385b loci, an additional PCR was carried out (Kittler et al, 2003) and analyzed on an ABI PRISM 377 DNA sequencer (Applied Biosystems).…”

Y Chromosome STR Haplotypes and the Genetic Structure of U.S. Populations of African, European, and Hispanic Ancestry

“…For DYS385, which is a duplicated Y-STR locus, the allele locus assignment was performed so that for each individual, the smaller allele was assigned to one locus (DYS385a) and the longer to the other (DYS385b). This procedure may result in incorrect genotypes (Kittler et al 2003); we therefore repeated relevant analyses without DYS385a/b, and in no case did the conclusions change. …”