Persistent Link:
http://hdl.handle.net/10150/195184
Title:
THE MOLECULAR EVOLUTION OF INNATE IMMUNITY GENES
Author:
Wlasiuk Battagliotti, Gabriela
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:
It is not clear whether genes of the innate immune system of vertebrates are subject to the same selective pressures as genes of the adaptive immune system, despite the fact that innate immunity genes lie directly at the interface between host and pathogens. The lack of consensus about the incidence, type, and strength of selection acting on vertebrate innate immunity genes motivated this study. The goal of this work was to elucidate the general principles of innate immune receptor evolution within and between species. A phylogenetic analysis of the Toll-like receptor 5 (TLR5) in primates showed an excess of nonsynonymous substitutions at certain codons, a pattern that is consistent with recurrent positive selection. The putative sites under selection often displayed radical substitutions, independent parallel changes, and were located in functionally important regions of the protein. In contrast with this interspecific pattern, population genetic analysis of this gene in humans and chimpanzees did not provide conclusive evidence of recent selection. The frequency and distribution of a TLR5 null mutation in human populations further suggested that TLR5 function might be partially redundant in the human immune system (Appendix A). Comparable analyses of the remaining nine human TLRs produced similar results and further pointed to a biologically meaningful difference in the pattern of molecular evolution between TLRs specialized in the recognition of viral nucleic acids and the other TLRs (Appendix B). The general picture that emerges from these studies challenges the conventional idea that pattern recognition receptors are subject to an extreme degree of functional constraint dictated by the recognition of molecules that are essential for microbial fitness. Instead, TLRs display patterns of substitution between species that reflect an old history of positive selection in primates. A common theme, however, is that only a restricted proportion of sites is under positive selection, indicating an equally important role for purifying selection as a conservative force in the evolution of this gene family. A comparative analysis of evolutionary rates at fifteen loci involved in innate, intrinsic and adaptive immunity, and mating systems revealed that more promiscuous species are on average under stronger selection at defense genes (Appendix C). Although the effect is weak, this suggests that sexual promiscuity plays some role in the evolution of immune loci by affecting the risk of contracting infectious diseases.
Type:
text; Electronic Dissertation
Keywords:
Innate immunity; mating system; Molecular evolution; primates; TLR; Toll-like receptors
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.titleTHE MOLECULAR EVOLUTION OF INNATE IMMUNITY GENESen_US
dc.creatorWlasiuk Battagliotti, Gabrielaen_US
dc.contributor.authorWlasiuk Battagliotti, Gabrielaen_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.abstractIt is not clear whether genes of the innate immune system of vertebrates are subject to the same selective pressures as genes of the adaptive immune system, despite the fact that innate immunity genes lie directly at the interface between host and pathogens. The lack of consensus about the incidence, type, and strength of selection acting on vertebrate innate immunity genes motivated this study. The goal of this work was to elucidate the general principles of innate immune receptor evolution within and between species. A phylogenetic analysis of the Toll-like receptor 5 (TLR5) in primates showed an excess of nonsynonymous substitutions at certain codons, a pattern that is consistent with recurrent positive selection. The putative sites under selection often displayed radical substitutions, independent parallel changes, and were located in functionally important regions of the protein. In contrast with this interspecific pattern, population genetic analysis of this gene in humans and chimpanzees did not provide conclusive evidence of recent selection. The frequency and distribution of a TLR5 null mutation in human populations further suggested that TLR5 function might be partially redundant in the human immune system (Appendix A). Comparable analyses of the remaining nine human TLRs produced similar results and further pointed to a biologically meaningful difference in the pattern of molecular evolution between TLRs specialized in the recognition of viral nucleic acids and the other TLRs (Appendix B). The general picture that emerges from these studies challenges the conventional idea that pattern recognition receptors are subject to an extreme degree of functional constraint dictated by the recognition of molecules that are essential for microbial fitness. Instead, TLRs display patterns of substitution between species that reflect an old history of positive selection in primates. A common theme, however, is that only a restricted proportion of sites is under positive selection, indicating an equally important role for purifying selection as a conservative force in the evolution of this gene family. A comparative analysis of evolutionary rates at fifteen loci involved in innate, intrinsic and adaptive immunity, and mating systems revealed that more promiscuous species are on average under stronger selection at defense genes (Appendix C). Although the effect is weak, this suggests that sexual promiscuity plays some role in the evolution of immune loci by affecting the risk of contracting infectious diseases.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectInnate immunityen_US
dc.subjectmating systemen_US
dc.subjectMolecular evolutionen_US
dc.subjectprimatesen_US
dc.subjectTLRen_US
dc.subjectToll-like receptorsen_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.committeememberHammer, Michael F.en_US
dc.contributor.committeememberMoran, Nancy A.en_US
dc.contributor.committeememberVercelli, Donataen_US
dc.contributor.committeememberWorobey, Michaelen_US
dc.identifier.proquest10706en_US
dc.identifier.oclc659753489en_US
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