Average difference in heterozygosity between closely related populations in regions surrounding putative new mutations (PNMs).

<p>PNMs are defined as derived variants that occur only once among 80 human chomosomes studied. The x-axis is heterozygosity in a less related outgroup population, quantified as total number of heterozyous sites in the 2 Kb window summed over all four individuals, while the y-axis is the difference in heterozygosity between the population in which the PNM was inferred and a closely related sister population, measured as average excess sites per individual. Reciprocal comparisons were conducted between two pairs of sister populations: Uta (open squares) and Tos (black squares) in Europe and Chb (grey crosses) and Jpt (grey circles) in east Asia. Outgroups were Jpt and Tos four Europe and East Asia respectively. In all cases, heterozygosity in the population in which the PNM was inferred is on average greater than in the control populaiton, this difference rising as heterozygosity increases in the outgroup. Results presented are weighted linearly by proximity to the putative new mutation, but an unweighted analysis yields essentially identical results.</p

Genetic divergence of 40 humans from the chimpanzee reference sequence according to genomic region.

<p>Divergence rates are quantified as the proportion of qualifying bases that differ with no adjustment for differences in rate of transition and transversions. Populations are: Africans sampled in Africa (black, ordered from left LWK, MKK, YRI), Africans sampled in America (ASW, grey) and non-Africans (open circles, four of each ordered from left TOS, CHB, JPT, UTA, GUJ, MXL). Panels are: all autosomes (Au); a randomly-selected medium sized autosome, chromosome 9 to compare with the X (C9); the X chromosome (X); the Y chromosome (Y, only half the samples are males). All autosomes yield very similar patterns with all Africans showing higher divergence than all non-Africans.</p

Dependence of Sequence Similarity among Flanking Sequences on AC Repeat Number

<p>The average number of matches shown (± standard error) quantifies similarity among three classes of sequence: (1) blocks of 50 bp lying immediately adjacent to a microsatellite; (2) blocks of 50 bp chosen randomly to lie between 500 and 600 bases downstream from a microsatellite; and (3) randomly selected blocks of 50 bp from around the genome. Average level of chance similarity in the genome is shown by a black line in each plot (comparison among class 3). 5′ and 3′ sequences are shown separately. Comparisons among sequence classes are shown for class 1 to class 1 (A), class 1 to class 2 for sequences at the same locus (B), class 1 to class 2 for sequences at different loci (C), and class 1 to class 3 (D).</p

Frequency Distribution of the 16 Possible Microsatellite-Flanking 5′–3′ Base Combinations Relative to Random Expectation

<div><p>(A) Cassette frequencies around (AC)₂ microsatellites: black bars, observed; white bars, expected. Error bars show 95% confidence intervals and asterisks indicate significant difference (<i>χ²</i> tests, 1 d.f. <i>p</i> < 0.05 with sequential Bonferroni corrections).</p> <p>(B) Deviation of cassette frequencies from random expectations around (AC)₂, (AC)₅, and (AC)₁₀ microsatellites: black, white, and hatched bars, respectively.</p> <p>(C) Sampled number (solid line) and proportion (dotted line) of microsatellites with cassette T/A as a function of microsatellite length.</p></div

Dependence of Dinucleotide Pattern Strength on the Presence of Repeat Clusters

<p>Beginning with the dataset from the scenario showing strong patterning and large sample size (cassette T/A, dinucleotide AT, (AC)₅; see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020199#pbio-0020199-g005" target="_blank">Figure 5</a>C), flanking sequences containing (AT)<i>_x</i> were excluded, where <i>x</i> equalled 2 or more (A), 3 or more (B), 4 or more (C), and 5 or more (D). Plotting conventions are the same as for <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020199#pbio-0020199-g004" target="_blank">Figure 4</a>.</p

Frequency Distribution of Isolated, Pure (AC)<i>_n</i> Microsatellite Lengths (in Repeat Units) in the Human Genome

<p>Black shading indicates numbers of microsatellites used for analyses in this study.</p

Dependence of Dinucleotide Flanking Sequence Patterning on AC Repeat Number

<p>Plots are as described in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020199#pbio-0020199-g004" target="_blank">Figure 4</a>. The progression for dinucleotide AT is illustrated for the commonest cassette type, (T/A). (A–F) depict AT dinucleotide frequencies, where patterning is most extreme, and show how periodicity and amplitude increase towards a maximum at around (AC)₁₀ and decline thereafter.</p

Flanking Sequence Frequency Distributions for Six Representative Nucleotide–Cassette Combinations for (AC)₅ Microsatellites

<p>In each panel, the microsatellite is centrally placed, represented as a gap at position zero, and the cassette type, base, and number of sequences considered <i>(n)</i> are given. Frequency distributions are plotted with separate 95% confidence intervals for odd- and even-numbered positions (shading). Horizontal lines indicate mean frequencies for the 3′ and 5′ flanking regions, calculated separately. (A–F) illustrate the six main classes of patterning where either dinucleotide periodicity or 5′–3′ asymmetry are present, summarised for all cassette–base combinations in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020199#pbio-0020199-t001" target="_blank">Table 1</a>.</p

Location of Single AT Dinucleotide Motifs Relative to the Central AC Microsatellite in Flanking Sequences Lacking (AT)₂₊ Microsatellites

<p>Figure shows frequency of AT dinucleotides around all length classes of AC repeat microsatellites longer than (AC)₂ (5′ number of sequences, <i>n</i> = 2,924; 3′ number of sequences, <i>n</i> = 3,309), with significantly greater numbers at odd positions 5′ and even positions 3′. Data are for cassette T/A only. Error bars show upper 95% confidence limit.</p

Relationship between the Probability of Assigning (AC)₂ Microsatellite Flanking Sequences to Self and Proximity to the AC Microsatellite

<p>Solid line shows the probability of assignment back to self. Analysis is restricted to (AC)₂ flanking sequences and is based on an assignment window 25 nucleotides wide on each side of the microsatellite. Dotted line indicates assignment probability expected of random DNA sequences.</p