Population Genetics and Evolution of Innate Immunity in House Mice

Persistent Link:
http://hdl.handle.net/10150/194535
Title:
Population Genetics and Evolution of Innate Immunity in House Mice
Author:
Salcedo, Tovah
Issue Date:
2009
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Whole-genome studies of rates of protein evolution show that genes underlying reproduction and immunity tend to evolve faster than other genes, consistent with the frequent action of positive selection. The evolution of immunity has been well-studied at the interspecific level, but much remains unknown about the population-level dynamics of immunity. This project described genetic variation at immunity and non-immunity loci as well as variation among levels of infection for diverse pathogens in a natural population of mice from Tucson. Analysis of autosomal and X-linked loci in the native range of Mus domesticus, the species from which Tucson mice are primarily descended, revealed low levels of variation consistent with a recent population expansion, resulting in a slight excess of rare alleles across the genome. Genetic variation among a set of classical inbred strains represented a small fraction of wild variation. An overlapping set of genes sequenced in mice from Tucson revealed that there is significant introgression from Mus castaneus. After controlling for gene flow, Tucson mice showed evidence of a mild bottleneck that produced a slight excess of intermediate frequency alleles, but did not result in a dramatic loss of genetic variability. Most of the 15 pathogens and parasites studied in Tucson were found at low to intermediate frequency, and most mice had one to three infections, suggesting that there are many opportunities for host-pathogen coevolution, and a possible role for coinfection. A study of Fv-4, which confers resistance to murine leukemia viruses, confirmed that the resistance allele originated in M. castaneus and is now found at intermediate frequency in Tucson after introduction through gene flow. Finally, a study of the recently duplicated Ceacam1 and Ceacam2 genes, previously shown to be involved in resistance to mouse hepatitis virus (MHV), revealed that a gene conversion event moved a suite of mutations from Ceacam2 to Ceacam1. An elevated rate of protein evolution showed that Ceacam2 had experienced positive selection after duplication. Interestingly, there was no association between MHV antibody presence and Ceacam1 genotype in Tucson. This project showed that gene flow and gene conversion mediated resistance to infections in wild mice.
Type:
text; Electronic Dissertation
Keywords:
house mice; innate immunity; Mus musculus; population genetics
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Ecology & Evolutionary Biology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Nachman, Michael W.
Committee Chair:
Nachman, Michael W.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titlePopulation Genetics and Evolution of Innate Immunity in House Miceen_US
dc.creatorSalcedo, Tovahen_US
dc.contributor.authorSalcedo, Tovahen_US
dc.date.issued2009en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractWhole-genome studies of rates of protein evolution show that genes underlying reproduction and immunity tend to evolve faster than other genes, consistent with the frequent action of positive selection. The evolution of immunity has been well-studied at the interspecific level, but much remains unknown about the population-level dynamics of immunity. This project described genetic variation at immunity and non-immunity loci as well as variation among levels of infection for diverse pathogens in a natural population of mice from Tucson. Analysis of autosomal and X-linked loci in the native range of Mus domesticus, the species from which Tucson mice are primarily descended, revealed low levels of variation consistent with a recent population expansion, resulting in a slight excess of rare alleles across the genome. Genetic variation among a set of classical inbred strains represented a small fraction of wild variation. An overlapping set of genes sequenced in mice from Tucson revealed that there is significant introgression from Mus castaneus. After controlling for gene flow, Tucson mice showed evidence of a mild bottleneck that produced a slight excess of intermediate frequency alleles, but did not result in a dramatic loss of genetic variability. Most of the 15 pathogens and parasites studied in Tucson were found at low to intermediate frequency, and most mice had one to three infections, suggesting that there are many opportunities for host-pathogen coevolution, and a possible role for coinfection. A study of Fv-4, which confers resistance to murine leukemia viruses, confirmed that the resistance allele originated in M. castaneus and is now found at intermediate frequency in Tucson after introduction through gene flow. Finally, a study of the recently duplicated Ceacam1 and Ceacam2 genes, previously shown to be involved in resistance to mouse hepatitis virus (MHV), revealed that a gene conversion event moved a suite of mutations from Ceacam2 to Ceacam1. An elevated rate of protein evolution showed that Ceacam2 had experienced positive selection after duplication. Interestingly, there was no association between MHV antibody presence and Ceacam1 genotype in Tucson. This project showed that gene flow and gene conversion mediated resistance to infections in wild mice.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjecthouse miceen_US
dc.subjectinnate immunityen_US
dc.subjectMus musculusen_US
dc.subjectpopulation geneticsen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineEcology & Evolutionary Biologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorNachman, Michael W.en_US
dc.contributor.chairNachman, Michael W.en_US
dc.contributor.committeememberMoran, Nancy A.en_US
dc.contributor.committeememberHammer, Michael F.en_US
dc.contributor.committeememberWorobey, Michaelen_US
dc.identifier.proquest10796en_US
dc.identifier.oclc659753647en_US
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