Genome sequencing highlights the dynamic early history of dogs

To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11-16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary

Genome Sequencing Highlights Genes Under Selection and the Dynamic Early History of Dogs

Abstract To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we analyzed novel high-quality genome sequences of three gray wolves, one from each of three putative centers of dog domestication, two ancient dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. We find dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow, which confounds previous inferences of dog origins. In dogs, the domestication bottleneck was severe involving a 17 to 49-fold reduction in population size, a much stronger bottleneck than estimated previously from less intensive sequencing efforts. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was far larger than represented by modern wolf populations. Conditional on mutation rate, we narrow the plausible range for the date of initial dog domestication to an interval from 11 to 16 thousand years ago. This period predates the rise of agriculture and, along with new evidence from variation in amylase copy number, implies that the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that surprisingly, none of the extant wolf lineages from putative domestication centers are more closely related to dogs, and the sampled wolves instead form a sister monophyletic clade. This result, in combination with our finding of dogwolf admixture during the process of domestication, suggests a re-evaluation of past hypotheses of dog origin is necessary. Finally, we also detect signatures of selection, including evidence for selection on genes implicated in morphology, metabolism, and neural development. Uniquely, we find support for selective sweeps at regulatory sites suggesting gene regulatory changes played a critical role in dog domestication

The time scale of recombination rate evolution in great apes

We present three linkage-disequilibrium (LD)-based recombination maps generated using whole-genome sequence data from 10 Nigerian chimpanzees, 13 bonobos, and 15 western gorillas, collected as part of the Great Ape Genome Project (Prado-Martinez J, et al. 2013. Great ape genetic diversity and population history. Nature 499:471-475). We also identified species-specific recombination hotspots in each group using a modified LDhot framework, which greatly improves statistical power to detect hotspots at varying strengths. We show that fewer hotspots are shared among chimpanzee subspecies than within human populations, further narrowing the time scale of complete hotspot turnover. Further, using species-specific PRDM9 sequences to predict potential binding sites (PBS), we show higher predicted PRDM9 binding in recombination hotspots as compared to matched cold spot regions in multiple great ape species, including at least one chimpanzee subspecies. We found that correlations between broad-scale recombination rates decline more rapidly than nucleotide divergence between species. We also compared the skew of recombination rates at centromeres and telomeres between species and show a skew from chromosome means extending as far as 10-15Mb from chromosome ends. Further, we examined broad-scale recombination rate changes near a translocation in gorillas and found minimal differences as compared to other great ape species perhaps because the coordinates relative to the chromosome ends were unaffected. Finally, on the basis of multiple linear regression analysis, we found that various correlates of recombination rate persist throughout the African great apes including repeats, diversity, and divergence. Our study is the first to analyze within- And between-species genome-wide recombination rate variation in several close relatives

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Data from: Genome sequencing highlights the dynamic early history of dogs

To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11–16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary

freedman_2014_plosgenetics_vcffiles

Included in the tarball are merged vcf files, for individual autosomes, for the 6 canid genomes sequenced for and described in "Genome Sequencing Highlights the Dynamic Early History of Dogs", Freedman et al, PLoS Genetics 2014. Those are: Chinese wolf, Israeli wolf, Croatian wolf, Golden jackal, Dingo and Basenji.These files have been converted to boxer reference genome CanFam 3.1 coordinates (the original paper was in v. 3.0 coordinates). See Freedman et al. 2014 for a detailed description of filters

Demographic model of domestication.

<p>Divergence times, effective population sizes (<i>N_e</i>), and post-divergence gene flow inferred by <i>G-PhoCS</i> in joint analysis of the Boxer reference genome, and the sequenced genomes of two basal dog breeds, three wolves, and a golden jackal. The width of each population branch is proportional to inferred population size, and stated ranges of parameter estimates indicate 95% Bayesian credible intervals. Horizontal gray dashed lines indicate timing of lineage divergences, with associated means in bold, and 95% credible intervals in parentheses. Migration bands are shown in green with associated values indicating estimates of total migration rates, which equal the probability that a lineage will migrate through the band during the time period when the two populations co-occur. Panels show parameter estimates for (A) the population tree best supported by genome-wide sequence divergence (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004016#pgen-1004016-g004" target="_blank">Fig. 4A</a>) (B) a regional domestication model, and (C) a single wolf lineage origin model in which dogs diverged most recently from the Israeli wolf lineage (similar star-like divergences are found assuming alternative choices for the single wolf ancestor. Estimated divergence times and effective population sizes are calibrated assuming an average mutation rate of 1×10⁻⁸ substitutions per generation and an average generation time of three years. See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004016#pgen.1004016.s028" target="_blank">Text S9</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004016#pgen.1004016.s018" target="_blank">Table S12</a> for details.</p

Top 25 outlier regions identified using the FDR-based methodology using Δout F_ST, Δ Tajima’s D and validated with the 12-breed dog diversity panel (see text), with regions ranked according their respective maximum CMS_1-FDR statistic.

<p>Columns within “This study” are based on the sequencing data generated here, while those under “CanMap” are computed from a ~48k SNP data set for a large set of wolves and ancient/basal dog breeds [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005851#pgen.1005851.ref035" target="_blank">35</a>]. Heat map colors reflect upper percentiles of the calculated metrics, with warmer colors indicating higher percentiles. Overlaps with previous studies: 1, vonHoldt et al. 2010 [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005851#pgen.1005851.ref035" target="_blank">35</a>]; 2, Vaysse et al. (2011) [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005851#pgen.1005851.ref025" target="_blank">25</a>]; 3, Boyko et al. (2010) [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005851#pgen.1005851.ref023" target="_blank">23</a>]; and Axelsson et al. (2013), [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005851#pgen.1005851.ref027" target="_blank">27</a>]; with numbers indicating the joint percentile, F_ST, F_ST and region id, respectively for each study.</p

Neighbor-joining tree and admixture signatures from ABBA/BABA tests.

<p>(A) NJ tree constructed from genome-wide pairwise divergence, calculated using equation E8.1 in . All nodes have 100% bootstrap support. Dashed lines indicate admixture edges that were statistically significant in ABBA/BABA tests. (B) ABBA/BABA tests with significant Z-scores (values ≥3 are significant). All comparisons made are shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004016#pgen.1004016.s017" target="_blank">Table S11</a>. For each row, boldfaced labels indicate admixing lineages.</p