Multiple recurrent mutations at four human Y-chromosomal single nucleotide polymorphism sites in a 37 bp sequence tract on the ARDSDP1 pseudogene

Institute of Legal Medicine, Innsbruck Medical University, Innsbruck, Austria.
Forensic Science International: Genetics (Impact Factor: 4.6). 06/2013; DOI: 10.1016/j.fsigen.2013.05.010
Source: PubMed


The male-specific region of the human Y chromosome (MSY) is passed down clonally from father to son and mutation is the single driving force for Y-chromosomal diversification. The geographical distribution of MSY variation is non-random. Therefore, Y-chromosomal single nucleotide polymorphisms (Y-SNPs) are of forensic interest, as they can be utilized, e.g. for deducing the bio-geographical origin of biological evidence. This extra information can complement short tandem repeat data in criminal investigations. For forensic applications, however, any targeted marker has to be unequivocally interpretable. Here, we report findings for 17 samples from a population study comprising specimens from ∼3700 men living in Tyrol (Austria), indicating apparent homoplasic mutations at four Y-SNP loci on haplogroup R-M412/L51/S167, R-U152/S28, and L-M20 Y chromosomes. The affected Y-SNPs P41, P37, L202, and L203 mapped to a 37bp region on Yq11.21. Observing in multiple phylogenetic contexts up to four homoplasic mutations within such a short sequence tract is unlikely to result from a series of independent parallel mutations. Hence, we rather propose X-to-Y gene conversion as a more likely scenario. Practical implications arising from markers exhibiting paralogues on the Y chromosome or sites with a high propensity to recurrent mutation for database searches are addressed.

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    • "The view that MSY is a genetically isolated region has been recently dismissed due to the discovery that X-to-Y gene conversion may occur in humans (Rosser et al. 2009; Cruciani et al. 2010; Trombetta et al. 2010). Despite increasing evidence indicating X–Y concerted evolution (Rosser et al. 2009; Iwase et al. 2010; Trombetta et al. 2010; Ellegren 2011; Niederstätter et al. 2013), the study of the dynamics of this molecular mechanism in humans is still in its infancy, and the pervasiveness of X–Y gene conversion in the evolution of human sex chromosomes has yet to be exhaustively explored. A history of gene conversion between paralogous (or gametologous ) sequences can be easily detected by examining a four-way alignment of paralogous (or gametologous) and orthologous regions from two closely related species (Osada and Innan 2008; Kijima and Innan 2010). "
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    ABSTRACT: It has long been believed that the Male Specific region of the human Y chromosome (MSY) is genetically independent from the X chromosome. This idea has been recently dismissed due to the discovery that X-Y gametologous gene conversion may occur. However, the pervasiveness of this molecular process in the evolution of sex chromosomes has yet to be exhaustively analyzed. In this study, we explored how pervasive X-Y gene conversion has been during the evolution of the youngest stratum of the human sex chromosomes. By comparing about 0.5 Mb of human-chimpanzee gametologous sequences, we identified 19 regions in which extensive gene conversion has occurred. From our analysis, two major features of these emerged: 1) several of them are evolutionarily conserved between the two species and 2) almost all of the nineteen hotspots overlap with regions where X-Y crossing-over has been previously reported to be involved in sex reversal. Furthermore, in order to explore the dynamics of X-Y gametologous conversion in recent human evolution, we re-sequenced these nineteen hotspots in 68 widely divergent Y haplogroups, and used publicly available SNP data for the X chromosome. We found that at least ten hotspots are still active in humans. Hence, the results of the interspecific analysis are consistent with the hypothesis of widespread reticulate evolution within gametologous sequences in the differentiation of hominini sex chromosomes. In turn, intraspecific analysis demonstrates that X-Y gene conversion may modulate human sex-chromosome-sequence evolution to a greater extent than previously thought.
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    ABSTRACT: Sampling of the human Y chromosome eliminates the curious disparity in ages of our last common male and female ancestors.
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    ABSTRACT: During the past few decades, a wealth of studies dedicated to the human Y-chromosome and its DNA variation, in particular single-nucleotide polymorphisms (Y-SNPs), has led to the construction of a well-established Y-chromosome phylogeny. Since the recent advent of new sequencing technologies, the discovery of additional Y-SNPs is exploding and their continuous incorporation in the phylogenetic tree is leading to an ever higher resolution. However, the large and increasing amount of information included in the 'complete' Y-chromosome phylogeny, which now already includes many thousands of identified Y-SNPs, can be overwhelming and complicates its understanding as well as the task of selecting suitable markers for genotyping purposes in evolutionary, demographic, anthropological, genealogical, medical and forensic studies. As a solution, we introduce a concise reference phylogeny whereby we do not aim to provide an exhaustive tree that includes all known Y-SNPs but, rather, a quite stable reference tree aiming for optimal global discrimination capacity based on a strongly reduced set that includes only the most resolving Y-SNPs. Furthermore, with this reference tree we wish to propose a common standard for Y-marker as well as Y-haplogroup nomenclature. The current version of our tree is based on a core set of 417 branch-defining Y-SNPs and is available online at This article is protected by copyright. All rights reserved.
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