Stand und Tendenzen der DV-Unterstützung der zentralen Universitätsverwaltung

<p>The red points illustrate the locations of the orthologs (including the orthologs with <i>e</i> = 0) on the horizontal axis, and the black lines represent the divergence scores (<i>e</i>) of these orthologs on the vertical axis. The area of elevated evolutionary distance on the beggining portion of Chromosome 1 corresponds to an area with significant differences in linkage disequilibrium between Indian-derived and Chinese rhesus macaques [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123624#pone.0123624.ref013" target="_blank">13</a>].</p

The 90% posterior credibility intervals of the chromosomal random effects from the gamma sub-model of the zero-inflated gamma regression.

<p>The value ‘Mu’ is the partially-pooled mean estimate across chromosomes. We see that there is fairly significant heterogeneity in mean evolutionary divergence of amino acid sequences across chromosomes, with chromosomes 5, 6, and 17 showing reduced evolutionary divergence, and chromosomes 8, 13, 19, and 20 showing increased evolutionary divergence.</p

Evolutionary distance between Indian and Chinese rhesus macaque orthologs, localized on the Indian rhesus macaque draft sequence (Chromosomes 15 through 20, and X).

<p>The red points illustrate the locations of the orthologs (including the orthologs with <i>e</i> = 0) on the horizontal axis, and the black lines represent the divergence scores (<i>e</i>) of these orthologs on the vertical axis. Chromosome 19 shows consistently high evolutionary divergence.</p

Evolutionary Distance of Amino Acid Sequence Orthologs across Macaque Subspecies: Identifying Candidate Genes for SIV Resistance in Chinese Rhesus Macaques

<div><p>We use the Reciprocal Smallest Distance (RSD) algorithm to identify amino acid sequence orthologs in the Chinese and Indian rhesus macaque draft sequences and estimate the evolutionary distance between such orthologs. We then use GOanna to map gene function annotations and human gene identifiers to the rhesus macaque amino acid sequences. We conclude methodologically by cross-tabulating a list of amino acid orthologs with large divergence scores with a list of genes known to be involved in SIV or HIV pathogenesis. We find that many of the amino acid sequences with large evolutionary divergence scores, as calculated by the RSD algorithm, have been shown to be related to HIV pathogenesis in previous laboratory studies. Four of the strongest candidate genes for SIV_<i>mac</i> resistance in Chinese rhesus macaques identified in this study are <i>CDK</i>9, <i>CXCL</i>12, <i>TRIM</i>21, and <i>TRIM</i>32. Additionally, <i>ANKRD</i>30<i>A</i>, <i>CTSZ</i>, <i>GORASP</i>2, <i>GTF</i>2<i>H</i>1, <i>IL</i>13<i>RA</i>1, <i>MUC</i>16, <i>NMDAR</i>1, <i>Notch</i>1, <i>NT</i>5<i>M</i>, <i>PDCD</i>5, <i>RAD</i>50, and <i>TM</i>9<i>SF</i>2 were identified as possible candidates, among others. We failed to find many laboratory experiments contrasting the effects of Indian and Chinese orthologs at these sites on <i>SIV_mac</i> pathogenesis, but future comparative studies might hold fertile ground for research into the biological mechanisms underlying innate resistance to <i>SIV_mac</i> in Chinese rhesus macaques.</p></div

Synteny maps between Chinese and Indian rhesus macaque reference sequences.

<p>The large-scale concordance serves to verify that the RSD algorithm is functioning to accurately map orthologous sequences. Each colored line maps an amino acid sequence in the Indian rhesus macaque draft sequence (top) to its corresponding ortholog on the Chinese rhesus macaque draft sequence (bottom). Diagonal lines illustrate transpositions; thin diagonal lines are indicative of single amino acid transposition, and thicker diagonal lines are indicative of block transpositions. The differing colors on each chromosome serve to illustrate the blocks in which synteny is fully conserved. Most chromosomes show almost fully conserved synteny, but chromosomes 15 and 16 show fairly large-scale rearrangement.</p

Table 1 presents the 20 genes that have been linked to HIV pathogenesis in previous studies [20–25] and also have highly divergent orthologs across Chinese and Indian rhesus macaques.

<p>The label “GOname” indicates the gene name assigned by GOanna. The labels “ProteinID.IR” and “ProteinID.CR” indicate the name of the amino acid sequence in the Indian and Chinese rhesus macaque draft sequence files, respectively. The label “<i>e</i>” is the estimate of evolutionary distance produced by the RSD alogirthm via implentation of PAML [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123624#pone.0123624.ref017" target="_blank">17</a>]. Finally, the labels “Chr.IR” and “Chr.CR” indicate the chromosome on which the amino acid sequences occur in the Indian and Chinese rhesus macaque draft sequence files, respectively.</p

Table 3 presents the 20 gene ontology (GO) categories (of the 176 GO categories containing at least 100 genes) with the highest median levels of divergence according to the RSD algorithm.

<p>The label “Zeros” refers to the number of genes in the GO category with a divergence score of zero. The label “N” refers to the number of genes in the GO category. GO categories related to viral processes and immunity are well represented among the GO categories that are diverging at higher rates relative to most other categories. We note that 3 of the 20 (15%) most divergent GO categories are related to viral processes or immunity, while only 2 of the other 156 (1%) of GO categories are related to viral processes or immunity. Table 3 is a subset of Supplementary <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123624#pone.0123624.s003" target="_blank">S3 Table</a>.</p