Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences

Abstract

We report the sequences of 1,244 human Y chromosomes randomly ascertained from 26 worldwide populations by the 1000 Genomes Project. We discovered more than 65,000 variants, including SNVs, MNVs, indels, STRs, and CNVs. Of these, CNVs contribute the greatest predicted functional impact. We constructed a calibrated phylogenetic tree based on binary SNVs and projected the more complex variants onto it, estimating the numbers of mutations for each class. Our phylogeny reveals bursts of extreme expansions in male numbers that have occurred independently among each of the five continental superpopulations examined, at times of known migrations and technological innovations.

Copy number variation arising from gene conversion on the human Y chromosome

“…Examination of the Y-chromosomal phylogeny established for these samples using Y-SNP variation (Poznik et al 2016) showed that, as expected, the different copy numbers of TTTY22-CNV were often clustered in branches of the phylogeny, so that the number of mutational events inferred was just 20 (Fig. 2, and see below for further details), nevertheless indicating a relatively high mutation rate compared with SNPs.…”

“…Samples with three copies showed the latter pattern plus a separate, additional fibre-FISH signal, and are described separately below. Finally, 10x Genomics Chromium linked-read data (Zheng et al 2016) were available for samples with one and two copies; the sample with one copy shows uniform distributions of barcode sharing and read depth across both TTTY22-CNV locations, while the sample with two copies shows increased barcode sharing and read depth in IR3 proximal and decreased sharing and depth in IR3 distal (Fig. S2).…”

“…The male-specific region of the Y chromosome offers unique opportunities for investigating both CNV and gene conversion, because (1) it is particularly tolerant of genetic variation (Poznik et al 2016), so a wide variety of variants persist in the population and (2) the lack of recombination between different Y lineages allows the history of variants to be identified from the phylogeny (Jobling 2008;Jobling and Tyler-Smith 2017;Massaia and Xue 2017;Trombetta and Cruciani 2017). We have previously described the genetic variation in a set of 1244 diverse worldwide Y chromosomes sequenced in phase 3 of the 1000 Genomes Project, including the identification and validation of 110 CNVs (Poznik et al 2016).…”

“…1a). Variation in copy number of this additional segment was initially identified using Genome STRiP and validated by array-CGH (Poznik et al 2016), revealing 0-3 copies, compared with the single copy in the reference sequence. TTTY22-CNV was further validated here by establishing a PCR assay using one pair of flanking primers which generated a 568 bp product in the absence of the TTTY22-CNV, and one pair within TTTY22 which generated a 249 bp product in its presence (Table S1).…”

“…We have previously described the genetic variation in a set of 1244 diverse worldwide Y chromosomes sequenced in phase 3 of the 1000 Genomes Project, including the identification and validation of 110 CNVs (Poznik et al 2016). The current study presents a detailed analysis of one of these, dbVar ID esv3818053 [chrY: 9,640,653,590 GRCh37 (hg19);chrY: 9,802,815,981,GRCh38 (hg38)], here designated by the more descriptive name TTTY22-CNV, because it overlaps with ~ 85% of this lincRNA gene and changes the number of its functional copies.…”