The Evolutionary Genetics of Life History in Drosophila Melanogaster
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University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2009 The Evolutionary Genetics of Life History in Drosophila Melanogaster Annalise B. Paaby University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Evolution Commons Recommended Citation Paaby, Annalise B., "The Evolutionary Genetics of Life History in Drosophila Melanogaster" (2009). Publicly Accessible Penn Dissertations. 35. https://repository.upenn.edu/edissertations/35 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/35 For more information, please contact [email protected]. The Evolutionary Genetics of Life History in Drosophila Melanogaster Abstract Life history traits are critical components of fitness and frequently reflect adaptive responses to environmental pressures. Natural populations of Drosophila melanogaster exhibit patterns of lifespan, fecundity, development time, body size and stress resistance that vary predictably along environmental gradients. Artificial selection studies, genetic correlation analyses, and quantitative trait mapping efforts have demonstrated a genetic basis for the observed phenotypic variation, but few genes have been identified that contribute ot natural life history variation. This work employs a candidate gene approach to discover genes and specific polymorphisms that contribute ot genetic variance for D. melanogaster life history. Three aging genes, which have been characterized to mediate longevity, reproduction and stress tolerance, have been evaluated for natural genetic variation from samples derived from the wild. Allelic variation at one gene, methuselah (mth), shows functional effects on lifespan, lifetime fecundity and resistance to oxidative stress. A polymorphism in the mth promoter has been identified which may contribute to variation in these traits by affecting levels of gene expression. Natural genetic variation at two genes in the insulin signaling pathway reveals a history of positive selection at the Insulin-like Receptor (InR), but evidence of neutral evolution at the InR substrate, chico. Furthermore, an indel polymorphism in the first exon of InR shows striking, nonrandom distributions on two continents, a sign that it may contribute to the observed patterns of phenotypic variation across these same habitats. Functional evaluation of alternate InR alleles demonstrates predictable effects on phenotype and levels of insulin signaling, which implicates this polymorphism in the adaptive evolution of wild D. melanogaster populations. These findings provide novel examples of how allelic variation underlies adaptive changes in life history evolution, and contribute complementary characterization of genetic function to the biology of aging. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Biology First Advisor Paul S. Schmidt Keywords life history, lifespan, genetic variation, natural populations, Drosophila Subject Categories Evolution This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/35 THE EVOLUTIONARY GENETICS OF LIFE HISTORY IN DROSOPHILA MELANOGASTER Annalise B. Paaby A DISSERTATION in Biology Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2009 Supervisor of Dissertation: Graduate Group Chairperson: ___________________________ ___________________________ Paul S. Schmidt Paul D. Sniegowski Associate Professor of Biology Associate Professor of Biology Dissertation Committee: Nancy M. Bonini, Professor of Biology, University of Pennsylvania Arthur E. Dunham, Professor of Biology, University of Pennsylvania Warren J. Ewens, Professor of Biology, University of Pennsylvania Joshua B. Plotkin, Assistant Professor of Biology, University of Pennsylvania Paul S. Schmidt, Associate Professor of Biology, University of Pennsylvania Paul D. Sniegowski, Associate Professor of Biology, University of Pennsylvania Marc Tatar, Professor of Ecology and Evolutionary Biology, Brown University The evolutionary genetics of life history in Drosophila melanogaster COPYRIGHT Annalise B. Paaby 2009 ACKNOWLEDGEMENTS It is a pleasure to thank my thesis advisor, Paul Schmidt, whose generosity in both practical affairs and enthusiasm provided a bedrock foundation for this research, and who has been an inspirational mentor to me. I thank the members of my committee, Nancy Bonini, Art Dunham, Warren Ewens, Josh Plotkin, Paul Sniegowski and Marc Tatar, for their service; I am honored to have shared my work with them. Thanks to past and present members of the Schmidt lab for good-natured technical assistance and good-humored company, and thanks to many members of the Biology Department for support, both academic and social, which is remembered with affection. I am especially grateful to Peter Petraitis and Warren Ewens, who are peerless role models in the academia that I have come to love, and whose friendliness and encouragement is cherished. The research was improved by funding from the American Federation for Aging Research and the Binns-Williams Fund, and by collaboration with Australian colleagues Mark Blacket and Ary Hoffmann, whose excellent data were contributed with expedience and good spirit. It is much appreciated. Finally, I am indebted to my parents, ever supportive, and Andrew, ever patient, who continually reminds me of the rewards of intellectual curiosity and the pleasures of exploring it together. iii ABSTRACT THE EVOLUTIONARY GENETICS OF LIFE HISTORY IN DROSOPHILA MELANOGASTER Annalise B. Paaby Paul S. Schmidt Life history traits are critical components of fitness and frequently reflect adaptive responses to environmental pressures. Natural populations of Drosophila melanogaster exhibit patterns of lifespan, fecundity, development time, body size and stress resistance that vary predictably along environmental gradients. Artificial selection studies, genetic correlation analyses, and quantitative trait mapping efforts have demonstrated a genetic basis for the observed phenotypic variation, but few genes have been identified that contribute to natural life history variation. This work employs a candidate gene approach to discover genes and specific polymorphisms that contribute to genetic variance for D. melanogaster life history. Three aging genes, which have been characterized to mediate longevity, reproduction and stress tolerance, have been evaluated for natural genetic variation from samples derived from the wild. Allelic variation at one gene, methuselah (mth), shows functional effects on lifespan, lifetime fecundity and resistance to oxidative stress. A polymorphism in the mth promoter has been identified which may contribute to variation in these traits by affecting levels of gene expression. Natural genetic variation at two genes in the insulin signaling iv pathway reveals a history of positive selection at the Insulin-like Receptor (InR), but evidence of neutral evolution at the InR substrate, chico. Furthermore, an indel polymorphism in the first exon of InR shows striking, nonrandom distributions on two continents, a sign that it may contribute to the observed patterns of phenotypic variation across these same habitats. Functional evaluation of alternate InR alleles demonstrates predictable effects on phenotype and levels of insulin signaling, which implicates this polymorphism in the adaptive evolution of wild D. melanogaster populations. These findings provide novel examples of how allelic variation underlies adaptive changes in life history evolution, and contribute complementary characterization of genetic function to the biology of aging. v TABLE OF CONTENTS List of Tables vii List of Figures viii Chapter One 1 Introduction Chapter Two 8 Functional Significance of Allelic Variation at methuselah, an Aging Gene in Drosophila Chapter Three 30 Nucleotide Variation in the methuselah Promoter May Include Functional Polymorphisms Affecting Drosophila Life History Chapter Four 46 Identification of a Candidate Adaptive Polymorphism for Drosophila Life History by Parallel Independent Clines on Two Continents Chapter Five 77 Characterization of an Adaptive Polymorphism in the Drosophila Insulin Receptor Chapter Six 105 Dissecting the Genetics of Longevity in Drosophila melanogaster Literature Cited 134 vi LIST OF TABLES Chapter Two Table 1. Statistical results for the lifespan assay 22 Table 2. Statistical results for the fecundity assay 23 Table 3. Statistical results for the oxidative stress assay 23 Table S1. Phenotype means for the three lab-derived mth alleles 29 Chapter Four Table 1. Results for the regression analyses for allele frequencies across latitude 69 Table 2. Results of the assays testing for functional differences between InR alleles 70 Table 3. Results of the MacDonald-Kreitman test for divergence at InR and chico 70 Chapter Five Table 1. Statistical results for the fecundity, lifespan and development time assays 95 Table 2. Statistical results for the Mount Sinai body weight and size assays 97 Table 3. Statistical results for the Bowdoinham body weight and size assays 98 Table 4. Statistical results for the stress assays 99 Chapter Six Table 1. Characterization of genes that extend lifespan when activity is decreased 110 Table 2. Characterization of genes that extend lifespan when activity is increased 112 Table 3. Characterization of genes showing allelic variation for