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Evolutionary distance of amino acid sequence orthologs across macaque subspecies: identifying candidate genes for SIV resistance in Chinese rhesus macaques.

Ross CT, Roodgar M, Smith DG - PLoS ONE (2015)

Bottom Line: Four of the strongest candidate genes for SIVmac resistance in Chinese rhesus macaques identified in this study are CDK9, CXCL12, TRIM21, and TRIM32.Additionally, ANKRD30A, CTSZ, GORASP2, GTF2H1, IL13RA1, MUC16, NMDAR1, Notch1, NT5M, PDCD5, RAD50, and TM9SF2 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 SIVmac pathogenesis, but future comparative studies might hold fertile ground for research into the biological mechanisms underlying innate resistance to SIVmac in Chinese rhesus macaques.

View Article: PubMed Central - PubMed

Affiliation: Department of Anthropology, University of California, Davis. Davis, United States of America; Molecular Anthropology Laboratory, University of California, Davis. Davis, United States of America.

ABSTRACT
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 SIVmac resistance in Chinese rhesus macaques identified in this study are CDK9, CXCL12, TRIM21, and TRIM32. Additionally, ANKRD30A, CTSZ, GORASP2, GTF2H1, IL13RA1, MUC16, NMDAR1, Notch1, NT5M, PDCD5, RAD50, and TM9SF2 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 SIVmac pathogenesis, but future comparative studies might hold fertile ground for research into the biological mechanisms underlying innate resistance to SIVmac in Chinese rhesus macaques.

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Related in: MedlinePlus

Evolutionary distance between Indian and Chinese rhesus macaque orthologs, localized on the Indian rhesus macaque draft sequence (Chromosomes 15 through 20, and X).The red points illustrate the locations of the orthologs (including the orthologs with e = 0) on the horizontal axis, and the black lines represent the divergence scores (e) of these orthologs on the vertical axis. Chromosome 19 shows consistently high evolutionary divergence.
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pone.0123624.g004: Evolutionary distance between Indian and Chinese rhesus macaque orthologs, localized on the Indian rhesus macaque draft sequence (Chromosomes 15 through 20, and X).The red points illustrate the locations of the orthologs (including the orthologs with e = 0) on the horizontal axis, and the black lines represent the divergence scores (e) of these orthologs on the vertical axis. Chromosome 19 shows consistently high evolutionary divergence.

Mentions: Figs 2–4 present estimates of evolutionary distance between the Chinese and Indian amino acid sequences as a function of chromosomal location in megabases (Mb). Amino acid sequence divergence levels appear to show weak signs of concentration into regions on a chromosome, although the extent to which this pattern holds may be confounded by the clustering of amino acid sequences themselves into specific regions on each chromosome. To better estimate chromosomal position effects, we use a multi-level, zero-inflated gamma regression model, with random effects on chromosomal position generated using a Gaussian process. Across chromosomes, we see very little evidence for strong chromosomal position effects, as there is very little difference in the estimated probability of a non-zero evolutionary distance or the mean value of evolutionary distance as a function of chromosomal position. These results are plotted in Figs 5–8.


Evolutionary distance of amino acid sequence orthologs across macaque subspecies: identifying candidate genes for SIV resistance in Chinese rhesus macaques.

Ross CT, Roodgar M, Smith DG - PLoS ONE (2015)

Evolutionary distance between Indian and Chinese rhesus macaque orthologs, localized on the Indian rhesus macaque draft sequence (Chromosomes 15 through 20, and X).The red points illustrate the locations of the orthologs (including the orthologs with e = 0) on the horizontal axis, and the black lines represent the divergence scores (e) of these orthologs on the vertical axis. Chromosome 19 shows consistently high evolutionary divergence.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401517&req=5

pone.0123624.g004: Evolutionary distance between Indian and Chinese rhesus macaque orthologs, localized on the Indian rhesus macaque draft sequence (Chromosomes 15 through 20, and X).The red points illustrate the locations of the orthologs (including the orthologs with e = 0) on the horizontal axis, and the black lines represent the divergence scores (e) of these orthologs on the vertical axis. Chromosome 19 shows consistently high evolutionary divergence.
Mentions: Figs 2–4 present estimates of evolutionary distance between the Chinese and Indian amino acid sequences as a function of chromosomal location in megabases (Mb). Amino acid sequence divergence levels appear to show weak signs of concentration into regions on a chromosome, although the extent to which this pattern holds may be confounded by the clustering of amino acid sequences themselves into specific regions on each chromosome. To better estimate chromosomal position effects, we use a multi-level, zero-inflated gamma regression model, with random effects on chromosomal position generated using a Gaussian process. Across chromosomes, we see very little evidence for strong chromosomal position effects, as there is very little difference in the estimated probability of a non-zero evolutionary distance or the mean value of evolutionary distance as a function of chromosomal position. These results are plotted in Figs 5–8.

Bottom Line: Four of the strongest candidate genes for SIVmac resistance in Chinese rhesus macaques identified in this study are CDK9, CXCL12, TRIM21, and TRIM32.Additionally, ANKRD30A, CTSZ, GORASP2, GTF2H1, IL13RA1, MUC16, NMDAR1, Notch1, NT5M, PDCD5, RAD50, and TM9SF2 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 SIVmac pathogenesis, but future comparative studies might hold fertile ground for research into the biological mechanisms underlying innate resistance to SIVmac in Chinese rhesus macaques.

View Article: PubMed Central - PubMed

Affiliation: Department of Anthropology, University of California, Davis. Davis, United States of America; Molecular Anthropology Laboratory, University of California, Davis. Davis, United States of America.

ABSTRACT
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 SIVmac resistance in Chinese rhesus macaques identified in this study are CDK9, CXCL12, TRIM21, and TRIM32. Additionally, ANKRD30A, CTSZ, GORASP2, GTF2H1, IL13RA1, MUC16, NMDAR1, Notch1, NT5M, PDCD5, RAD50, and TM9SF2 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 SIVmac pathogenesis, but future comparative studies might hold fertile ground for research into the biological mechanisms underlying innate resistance to SIVmac in Chinese rhesus macaques.

Show MeSH
Related in: MedlinePlus