Recombination dynamics of a human Y-chromosomal palindrome:rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions

The male-specific region of the human Y chromosome (MSY) includes eight large inverted repeats (palindromes) in which arm-to-arm similarity exceeds 99.9%, due to gene conversion activity. Here, we studied one of these palindromes, P6, in order to illuminate the dynamics of the gene conversion process. We genotyped ten paralogous sequence variants (PSVs) within the arms of P6 in 378 Y chromosomes whose evolutionary relationships within the SNP-defined Y phylogeny are known. This allowed the identification of 146 historical gene conversion events involving individual PSVs, occurring at a rate of 2.9-8.4×10(-4) events per generation. A consideration of the nature of nucleotide change and the ancestral state of each PSV showed that the conversion process was significantly biased towards the fixation of G or C nucleotides (GC-biased), and also towards the ancestral state. Determination of haplotypes by long-PCR allowed likely co-conversion of PSVs to be identified, and suggested that conversion tract lengths are large, with a mean of 2068 bp, and a maximum in excess of 9 kb. Despite the frequent formation of recombination intermediates implied by the rapid observed gene conversion activity, resolution via crossover is rare: only three inversions within P6 were detected in the sample. An analysis of chimpanzee and gorilla P6 orthologs showed that the ancestral state bias has existed in all three species, and comparison of human and chimpanzee sequences with the gorilla outgroup confirmed that GC bias of the conversion process has apparently been active in both the human and chimpanzee lineages

Schematic representation of the inversions identified within three haplogroups.

<p>The approximate position of each inversion is indicated by a red cross.</p

Location and structure of palindrome P6, showing positions of PSVs analysed.

<p>a) Idiogram of Y chromosome, showing positions of the 8 palindromes, with structure and coordinates (in GRCh37) of P6 below. b) Position and nature of the differences between the arms of P6, indicating the 10 SN-PSVs analysed, and the positions of PCR primers used in arm-specific amplifications. STSs marking the arm boundaries are also shown (with ‘sY’ prefixes). Asterisks indicate the two SN-PSVs identified from a haplogroup O3a chromosome.</p

Patterns of P6 nucleotide replacements in the human and chimpanzee lineages.

a<p>2×2 contingency table, Chi-square test with Yates correction.</p>*<p>p-value<0.05.</p>**<p>p-value<0.01.</p

Recognition of gene conversion, co-conversion and inversion events.

<p>a) Existence of three genotypes at a hypothetical PSV indicates that gene conversion has taken place, if recurrent mutation is neglected. Genotyping the PSV in a phylogenetic context, and applying the principle of maximum parsimony, allows the recognition of: b) Haplogroup descending from an ancestor in which the PSV mutation has not yet arisen (G/G), and is therefore uninformative; c) Haplogroup descending from an ancestor in which the PSV mutation has arisen (G/A), but shows no variation, and therefore no evidence for gene conversion; d) Haplogroup descending from an ancestor in which the PSV mutation has arisen, and shows evidence of at least two bidirectional conversion events (G/G and A/A); e) Recognition of co-conversion of more than one PSV requires ‘phase’ information, as does (f) recognition of inversions.</p

Inter-specific sequence divergence in arms and spacers of palindrome P6.

a<p>2×2 contingency table, Chi-square test with Yates correction.</p

Excavating past population structures by surname-based sampling: the genetic legacy of the Vikings in northwest

The genetic structures of past human populations are obscured by recent migrations and expansions and have been observed only indirectly by inference from modern samples. However, the unique link between a heritable cultural marker, the patrilineal surname, and a genetic marker, the Y chromosome, provides a means to target sets of modern individuals that might resemble populations at the time of surname establishment. As a test case, we studied samples from the Wirral Peninsula and West Lancashire, in northwest England. Place-names and archaeology show clear evidence of a past Viking presence, but heavy immigration and population growth since the industrial revolution are likely to have weakened the genetic signal of a 1,000-year-old Scandinavian contribution. Samples ascertained on the basis of 2 generations of residence were compared with independent samples based on known ancestry in the region plus the possession of a surname known from historical records to have been present there in medieval times. The Y-chromosomal haplotypes of these 2 sets of samples are significantly different, and in admixture analyses, the surnameascertained samples show markedly greater Scandinavian ancestry proportions, supporting the idea that northwest England was once heavily populated by Scandinavian settlers. The method of historical surname-based ascertainment promises to allow investigation of the influence of migration and drift over the last few centuries in changing the population structure of Britain and will have general utility in other regions where surnames are patrilineal and suitable historical records survive

A predominantly Neolithic origin for European paternal lineages.

none16The relative contributions to modern European populations of Paleolithic hunter-gatherers and Neolithic farmers from the Near East have been intensely debated. Haplogroup R1b1b2 (R-M269) is the commonest European Y-chromosomal lineage, increasing in frequency from east to west, and carried by 110 million European men. Previous studies suggested a Paleolithic origin, but here we show that the geographical distribution of its microsatellite diversity is best explained by spread from a single source in the Near East via Anatolia during the Neolithic. Taken with evidence on the origins of other haplogroups, this indicates that most European Y chromosomes originate in the Neolithic expansion. This reinterpretation makes Europe a prime example of how technological and cultural change is linked with the expansion of a Y-chromosomal lineage, and the contrast of this pattern with that shown by maternally inherited mitochondrial DNA suggests a unique role for males in the transition.noneBalaresque P.; Bowden G.R.; Adams S.M.; Leung H-Y.; King T.E.; Rosser Z.H.; Goodwin J.; Moisan J-P.; Richard C.; Millward A.; Demaine A.G.; Barbujani G.; Previderè C.; Wilson I.J.; Tyler-Smith C.; and Jobling M.A.Balaresque, P.; Bowden, G. R.; Adams, S. M.; Leung, H. Y.; King, T. E.; Rosser, Z. H.; Goodwin, J.; Moisan, J. P.; Richard, C.; Millward, A.; Demaine, A. G.; Barbujani, Guido; Previderè, C.; Wilson, I. J.; Tyler Smith, C.; Jobling, M. A