High-Resolution Pairwise Substitution Rate Estimates <i>(K)</i> across Promoter Region Alignments

<div><p>The <i>x-</i>axis denotes nucleotide position relative to the TSS reference position at +1 (grey vertical line). Error bars (lighter shading) show 95% confidence intervals for each data point.</p> <p>(A) Rates calculated from mouse-based alignments.</p> <p>(B) Rates calculated from human-based alignments.</p></div

Patterns of Evolution in Promoter Subcategories

<div><p>(A) The percentage of all mouse TSSs assigned to each category. Dark blue shows the percentage assigned to the category annotated to the left, and light blue the reciprocal category (e.g., non-CpG is the reciprocal of CpG). The colour coding is consistent with (B–E). The “map” category refers to whether the TSS could be mapped to the annotated 5′-most end of a known protein-coding gene (dark blue), could not mapped to a gene (light blue), or maps internally to an annotated gene extent (grey). See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020030#s3" target="_blank">Materials and Methods</a> for details of category assignment.</p> <p>(B–E) Single nucleotide resolution estimates of substitution rates calculated from promoters assigned to the indicated categories. Only rates calculated from mouse–dog comparisons are shown. The 95% confidence intervals have been excluded for clarity. Red horizontal lines show <i>K</i> for ARs, nucleotide position is shown on the <i>x-</i>axis relative to the TSS at +1 (grey vertical line), and <i>K</i> is shown on the <i>y-</i>axis. Although there are three categories indicated for gene mapping in (A), only two are shown for clarity.</p></div

Micro-Insertion and -Deletion Rates

<div><p>Promoter rates calculated as insertion (blue) and deletion (red) events per nucleotide in 100-bp consecutive windows (<i>x-</i>axis). Error bars show 95% confidence intervals; solid horizontal lines show rates calculated from AR alignments. Vertical grey line indicates the +1 TSS position.</p> <p>(A) Human rates based on alignments between human, chimpanzee, and macaque; rates shown are derived only from the human terminal branch (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020030#s3" target="_blank">Materials and Methods</a>).</p> <p>(B) Mouse terminal branch rates based on comparisons between mouse, rat, and dog.</p></div

Recombination Jungles and Deserts

<div><p>Enrichment of CCTCCCT motif in recombination jungles (upper panel). The standard deviation (SD) from the mean number of CCTCCCT motifs is plotted against recombination rate. Red bars are 1-Mb regions included in the top 10% recombination rate in both HS and RIs (recombination jungles), and blue bars are regions in the bottom 10% (recombination deserts).</p> <p>Histograms of human recombination rates for the orthologous regions of the mouse recombination jungles and deserts (lower panel).</p></div

Average Recombination Rates for All Chromosomes

<p>Rates for RIs are shown as a black line and for HS as a blue line. The ratio between the genetic distance and physical distance was calculated using a sliding window of 5 Mb and a shift of 2 Mb between windows centers, assuming a constant rate of recombination between two adjacent markers.</p

Sex-Specific Recombination Rates in the HS

<p>Average recombination rate for all chromosomes calculated similar to the HS sex-averaged map, for males (black line) and females (blue line).</p

Relation between LD Levels in Inbred Strains and Recombination Rates in HS and RIs on Chromosome 7

<p>The top figure is the recombination rate (cM/Mb) for the HS and RIs in 1-Mb non-overlapping windows across a 25-Mb region in Chromosome 7. Below, the six boxes represent the location of four recombination jungles (in red) and two deserts (in blue) of 1 Mb each. The bottom figure is the LD structure of the same region based on the SNP genotypes of 55 inbred strains. Each dot represents the pairwise LD level between two different SNPs. Regions of high LD measured by <i>r²</i> are in blue, whereas regions of linkage equilibrium are in red. As can be seen in this example, deserts tend to overlap with large blocks of LD, and jungles are typically located on the border of the blocks. The overlap proportion of the four recombination jungles with haplotype blocks is 0.00, 0.58, 0.55, and 0.35 for regions 1, 2, 5, and 6. The two deserts (3 and 4) overlap completely with haplotype blocks.</p

Sensitivity of VHL-1–Regulated Genes to Defects in Extracellular Matrix-Associated Proteins

<div><p>RNase protection assays showing altered expression of VHL-1–regulated genes that are HIF-1 independent (upper six panels) and HIF-1 dependent (F22B5.4) in worms bearing mutations affecting (A) procollagen prolyl and lysyl hydroxylases and (B) other extracellular matrix-associated proteins. A common pattern of upregulation is observed in <i>hif-1; vhl-1, vhl-1, dpy-18, let-268, gon-1, mig-17,</i> and <i>unc-6</i> worms but not other mutants. This contrasts with the HIF-1–dependent gene F22B5.4, which is upregulated in <i>vhl-1</i> worms but none of the other mutants.</p> <p>(C) RNase protection assay for C01B4.9 illustrating DPY-18–mediated changes in expression that are independent of HIF-1.</p></div

Responses of VHL-1–Dependent, HIF-1–Independent Genes to <i>egl-9</i> Inactivation, Hypoxia, and 2-Oxoglutarate Dioxygenase Inhibitors

<p>RNase protection assays showing regulation of VHL-1–dependent, HIF-1–independent genes by (A) EGL-9 and hypoxia and (B) pharmacological inhibitors of 2-oxoglutarate dioxygenases: DIP and DMOG. None of the genes is regulated by EGL-9, but two genes (C01B4.7 and C01B4.8) show modest induction by hypoxia, DIP, and DMOG.</p