Divergent Human Y-Chromosome Microsatellite Evolution Rates

Abstract

Abstract:In this work, we analyze several characteristics influencing the low variability of the microsatellite DYS19 in the major founder Amerindian Y chromosome lineage containing the point mutation DYS199-T. Variation of DYS19 was compared with that of five other Y-linked tetranucleotide repeat loci (DYS389A, DYS389B, DYS390, DYS391, and DYS393) in the DYS199-T lineage. All the other microsatellites showed significantly higher levels of variability than DYS19 as measured by gene diversity and repeat number variance. Moreover, we had previously shown that DYS19 had high diversity in Brazilians and in several other populations worldwide. Thus, the slow DYS19 evolution in the DYS199-T lineage seems to be both locus and allele specific. To understand the slow DYS19 evolutionary rate, the microsatellite loci were compared according to their mapping on the Y chromosome and also on the basis of structural aspects such as the base composition of the repeat motif and flanking regions and the degree of perfection and size (repeat number) of the variable blocks. The only observed difference that might be related to the low DYS19 variability is its small average number of repeats, a value expected to be closer to the founder DYS19 allele in the DYS199-T lineage. These data were also compared to other derived Y lineages. The Tat-C lineage displayed a lower DYS19 variability correlated to a small average repeat number, while in the DYS234-G lineage, a high DYS19 variability was found associated to a larger average repeat number. This approach reveals that evolution of Y microsatellites in lineages defined by slowly evolving markers, such as point mutations, can be greatly influenced by the size (number of repeats of the variable block) of the founder allele in each microsatellite locus. Thus lineage-dating methods using microsatellite variation should be practiced with great care.

Mutation rate estimates for 110 Y-chromosome STRs combining population and father–son pair data

“…21 Lower mutability of shorter alleles compared with longer ones has been observed several times. 32,33,12,34 Accordingly, our results show that the variation in meiosis mutation rates could be significantly explained by mean repeat count (Supplementary Tables S5 and S6). Furthermore, when no diversity variable is included in the model, both repeat count and repeat motif contribute independently to explain the mutation rate variability (ie, model m3, Supplementary Table S5).…”

“…Previous studies have failed to find a relationship of simple versus complex repeats with genetic diversity among loci. 38,32,22 These results might be due to the lack of effect of repeat structure. However, our qualitative classification of loci as 'simple' or 'complex' could be missing essential information of complex loci (ie, differential length of the homogeneous array or combination of variable and constant repeats 21 ) affecting the mutation rate.…”

“…Our approximation allows more detailed results by achieving an adjusted mutation rate for each locus separately. The same methodology could be used to estimate population or lineage-specific mutation rates, as different lineages and populations are often characterized by specific allele combinations 32,33,39 and mutation rate seems to be affected by allele size and structure. Finally, the analysis presented here can be easily automated for a database, allowing the updating of estimates when new population and meiosis data are incorporated from upcoming studies.…”

Haplogroup-specific deviation from the stepwise mutation model at the microsatellite loci DYS388 and DYS392

“…4,5,7,19 Short alleles with 10 triplets or fewer appear to mutate extremely seldom in human microsatellites. 5 This could be caused by physical constraints imposed by the DNA replication machinery.…”

“…Within the three haplogroups, allele distribution and variability at all six microsatellite loci were examined. As a measure of variability two parameters were used: 19 locus diversity D (calculated as gene diversity) and repeat number variance σ 2 . D and its sampling variance were estimated as described.…”