The vertebrate immune system includes numerous proteins involved in the recognition and elimination of parasitic organisms. In vertebrates, the most important system for eliminating intracellular parasites (such as viruses) involves presentation of parasite-derived peptides by class I major histocompatibility complex (MHC) molecules to cytotoxic T cells (CD8+TL). The general goals of this research are to understand the origin and evolution of key molecular components of the vertebrate immune system and to understand the evolution of molecular adaptations in parasitic organisms that evade recognition and elimination by the host's immune system. The methods used in this research involve statistical analysis of published DNA sequence data, of which a large amount is now available both for immune system genes and for genes of major human pathogens (particularly viruses). The purposes of these analyses are as follows: (1) to test the hypothesis that the recognition systems of vertebrate immunity have given rise to natural selection favoring amino acid sequence diversity in parasite protein regions that are targets for immune recognition, while parasites have correspondingly selection for variation in host immune system molecules;(2) to test the hypothesis that epitopes presented by the host MHC to CD8+TL are subject to conflicting selection pressures, including both selection to evade immune recognition and selection to conserve sequence patterns important for viral fitness;(3) to reconstruct patterns of recombination in the evolution of pathogenic viruses and bacteria;and (4) to use phylogenetic analyses of key immune system families, along with information regarding their expression and interactions, in order to reconstruct the evolutionary process whereby members of multi-gene families playing key roles in the immune system have become functionally differentiated. By increasing our understanding of how genetic variation enables pathogens to evade recognition and elimination by the human immune system, this research will provide basic knowledge useful in designing public health strategies to counteract important human pathogens such as human immunodeficiency virus 1 (HIV-1) and hepatitis C virus. In addition, by increasing our understanding of the population diversity and evolutionary history of human immune system genes, this research will enhance our knowledge of human immune function in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM043940-21
Application #
7787095
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
1990-09-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2012-03-31
Support Year
21
Fiscal Year
2010
Total Cost
$172,585
Indirect Cost
Name
University of South Carolina at Columbia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
041387846
City
Columbia
State
SC
Country
United States
Zip Code
29208
Putaporntip, C; Kuamsab, N; Kosuwin, R et al. (2016) Natural selection of K13 mutants of Plasmodium falciparum in response to artemisinin combination therapies in Thailand. Clin Microbiol Infect 22:285.e1-8
Hughes, Austin L (2015) Adaptive amino acid composition in collagens of parasitic nematodes. Infect Genet Evol 31:277-83
Hughes, Austin L (2014) Evolutionary diversification of aminopeptidase N in Lepidoptera by conserved clade-specific amino acid residues. Mol Phylogenet Evol 76:127-33
Hughes, Austin L; Friedman, Robert (2014) Evolutionary diversification of the vertebrate transferrin multi-gene family. Immunogenetics 66:651-61
Putaporntip, Chaturong; Hughes, Austin L; Jongwutiwes, Somchai (2013) Low level of sequence diversity at merozoite surface protein-1 locus of Plasmodium ovale curtisi and P. ovale wallikeri from Thai isolates. PLoS One 8:e58962
Hughes, Austin L (2013) Origin of Ecdysosteroid UDP-glycosyltransferases of Baculoviruses through Horizontal Gene Transfer from Lepidoptera. Coevolution 1:1-7
Hughes, Austin L (2013) Accumulation of slightly deleterious mutations in the mitochondrial genome: a hallmark of animal domestication. Gene 515:28-33
Hughes, Austin L (2012) Amino acid sequence coevolution in the insect bursicon ligand-receptor system. Mol Phylogenet Evol 63:617-24
Becker, Ericka A; Burns, Charles M; León, Enrique J et al. (2012) Experimental analysis of sources of error in evolutionary studies based on Roche/454 pyrosequencing of viral genomes. Genome Biol Evol 4:457-65
Hughes, Austin L; Becker, Ericka A; Lauck, Michael et al. (2012) SIV genome-wide pyrosequencing provides a comprehensive and unbiased view of variation within and outside CD8 T lymphocyte epitopes. PLoS One 7:e47818

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