Kittler Ralf, Erler Axel, Brauer Silke, Stoneking Mark, Kayser Manfred
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher platz 6, D-04103 Leipzig, Germany.
Eur J Hum Genet. 2003 Apr;11(4):304-14. doi: 10.1038/sj.ejhg.5200960.
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 approximately 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 chi(2)-test (chi(2)=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.
人类Y染色体展现出重复序列的异常含量。Y染色体重复序列是染色体内重组的潜在靶点，而染色体内重组被认为与许多Y染色体相关缺陷有关，比如男性不育。此类重排有可能通过使用位于重复单元内的高度多态性DNA标记（如微卫星）来进行研究。在此，我们分析了Y染色体微卫星DYS385的两个拷贝，我们鉴定出它们并将其定位到Yq11.223处一个约190 kb的重复且倒置的片段上。我们在一个德国人群样本（n = 70）中发现，该Y染色体短串联重复序列两个拷贝的等位基因频率分布之间存在高度显著的相关性（r = 0.853，P < 0.001），并且在卡方检验中差异不显著（χ2 = 15.45，P > 0.05）。在一个重复的高度多态性微卫星的两个拷贝之间，这种几乎相同的等位基因频率分布无法用产生微卫星等位基因的独立突变过程来解释。相反，这可能被解释为重复片段之间相互染色体内交换过程的证据。然而，使用更多人类群体以及更多Y染色体标记进行的更详细分析表明，这种现象具有高度的群体特异性，并且当结合两个Y单核苷酸多态性单倍群来分析Y染色体短串联重复序列多样性时，该现象完全消失。我们发现两个DYS385位点（以及其他Y染色体短串联重复序列）的多样性高度依赖于单倍群背景，并且德国样本中两个单倍群的比例相等解释了两个DYS385位点几乎相同的等位基因频率分布。因此，我们在此证明，暗示染色体内重组的重复位点的等位基因频率分布仅能由群体历史来解释。
