Putative mutator allele on chromosome 11.

<p>Relationship between the number of <i>de novo</i> mutations in the offspring and the maternal number of highly derived haplotypes of the putative mutator allele on chromosome 11 (a). Location of the putative mutator locus on chromosome 11, defined as a peak in the difference between the maximum and interquartile mean number of derived alleles across haplotypes (b).</p

Top 20 candidate mutator loci (relative to genome build hg19), ranked by residual.

<p>Top 20 candidate mutator loci (relative to genome build hg19), ranked by residual.</p

Simulation study.

<p>An example of simulated data showing a subset of haplotypes with a peak in the number of derived alleles in a 10 Kb sliding window. A region of 100 Kb was simulated over 40,000 generations using a coalescent approach with recombination. In this example a mutator allele with <i>ϕ</i> = 5 was introduced 20,000 generations before the present and was assumed to be weakly deleterious, with a selective coefficient of -0.0002. The red and green lines show the maximum and trimmed mean number of derived alleles in the window. Individual sampled haplotypes are shown in grey.</p

Relationship between the maximum and the interquartile mean number of derived alleles.

<p>A hexagon bin plot illustrating the relationship between the maximum and the interquartile mean number of derived alleles across all haplotypes in 10Kb windows from phase 3 of the G1K project. The data shown are for all populations combined, but the relationship is similar when populations are analyzed individually. The shading indicates the number of points within each hexagonal bin. The linear regression line is shown as a solid red line and the dashed red line identifies the candidate loci shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006549#pgen.1006549.t001" target="_blank">Table 1</a>. Note that each row of <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006549#pgen.1006549.t001" target="_blank">Table 1</a> can correspond to multiple points in the figure, due to multiple sliding windows overlapping the locus.</p

P-values (<i>p</i>_<i>t</i>, <i>p</i>_<i>perm</i>) from tests of elevated rate of <i>de novo</i> mutation in trios.

<p>P-values (<i>p</i>_<i>t</i>, <i>p</i>_<i>perm</i>) from tests of elevated rate of <i>de novo</i> mutation in trios.</p

A Genome-Wide Survey of Genetic Variation in Gorillas Using Reduced Representation Sequencing

<div><p>All non-human great apes are endangered in the wild, and it is therefore important to gain an understanding of their demography and genetic diversity. Whole genome assembly projects have provided an invaluable foundation for understanding genetics in all four genera, but to date genetic studies of multiple individuals within great ape species have largely been confined to mitochondrial DNA and a small number of other loci. Here, we present a genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies. We identify 3,006,670 polymorphic sites in 14 individuals: 12 western lowland gorillas (<i>Gorilla gorilla gorilla</i>) and 2 eastern lowland gorillas (<i>Gorilla beringei graueri</i>). We find that the two species are genetically distinct, based on levels of heterozygosity and patterns of allele sharing. Focusing on the western lowland population, we observe evidence for population substructure, and a deficit of rare genetic variants suggesting a recent episode of population contraction. In western lowland gorillas, there is an elevation of variation towards telomeres and centromeres on the chromosomal scale. On a finer scale, we find substantial variation in genetic diversity, including a marked reduction close to the major histocompatibility locus, perhaps indicative of recent strong selection there. These findings suggest that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline, perhaps associated with disease, has been a significant factor in recent and long-term pressures on wild gorilla populations.</p></div

Segregating sites in nine western lowland gorillas.

<p>A. Density of segregating sites in 1 Mbp bins. Sites passing quality and depth filtering thresholds in all nine gorillas BiKira, EB(JC), Fubu, Guy, Kamilah, Kesho, Matadi, Murphy and Ruby were binned in 1 Mb bins and the density of segregating sites calculated. Resulting densities are plotted on an ideogram, with the scale expressed as number of sites per kbp. B. Profile of mean segregating site density as a function of chromosomal position on both long and short arms, averaged over all chromosomes. Position is normalised by chromosome length, with the centromere at 0.0 and the telomere at 1.0 on both arms. An increase in genetic diversity is evident towards the centromere and telomere on both arms.</p

Allele frequency spectra.

<p>Conditional allele frequency spectra are shown for eight western lowland gorillas (red) and eight samples from each of three human populations: African (black), European (blue) and Asian (green). Spectra are conditioned on sites ascertained in one individual (and, for gorilla, averaged over all samples). The dashed line is the theoretical expectation for a constant population size. Error bars for the gorilla samples represent standard deviations.</p

Principal components analysis (PCA).

<p>A. PCA based on 123,591 polymorphic sites in 12 western lowland gorillas and two eastern lowland gorillas. Here, PC1 separates western gorillas from eastern gorillas. B. PCA based on 110,971 polymorphic sites in the 12 western lowland gorillas only.</p

Rates and ratios of heterozygous and homozygous variants in each of the gorillas sampled.

<p>Rates of heterozygous (light blue) and homozygous (dark blue) variants were called from sequence alignments against the gorilla reference genome and expressed as percentage rates. Note Kamilah’s low rate of homozygous variants, due to her providing the DNA from which the reference genome was assembled. The corresponding hom/het ratios (ratios of homozygous to heterozygous variant rates) show that eastern lowland gorillas (black) have higher ratios than western lowland gorillas (red). Additional data for Mukisi and EB(JC) (Mukisi_PvuII and EB_JC_PvuII) were taken from a previously published study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065066#pone.0065066-Scally1" target="_blank">[3]</a>.</p