Adaptive Evolution as a Predictor of Species-Specific Innate Immune Response

Molecular Biology and Evolution
Andrew E WebbMary J O'Connell

Abstract

It has been proposed that positive selection may be associated with protein functional change. For example, human and macaque have different outcomes to HIV infection and it has been shown that residues under positive selection in the macaque TRIM5α receptor locate to the region known to influence species-specific response to HIV. In general, however, the relationship between sequence and function has proven difficult to fully elucidate, and it is the role of large-scale studies to help bridge this gap in our understanding by revealing major patterns in the data that correlate genotype with function or phenotype. In this study, we investigate the level of species-specific positive selection in innate immune genes from human and mouse. In total, we analyzed 456 innate immune genes using codon-based models of evolution, comparing human, mouse, and 19 other vertebrate species to identify putative species-specific positive selection. Then we used population genomic data from the recently completed Neanderthal genome project, the 1000 human genomes project, and the 17 laboratory mouse genomes project to determine whether the residues that were putatively positively selected are fixed or variable in these populations. We find evidenc...Continue Reading

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Methods Mentioned

BETA
protein folding

Software Mentioned

RDP3
MrBayes
ProtTest
3SEQ
PAML
Ensembl BioMart
BOOTSCAN
codeML
MAXCHI
DnaSP

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