Population genetic approaches to detect natural selection in Drosophila melanogaster [Elektronische Ressource] / vorgelegt von Sascha Glinka

Sascha Glinka

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2005
• Nombre de lectures: 7
• Langue: English
• Poids de l'ouvrage: 6 Mo

Extrait

Population Genetic Approaches
to Detect Natural Selection in
Drosophila melanogaster
Dissertation
der Fakultät für Biologie der
Ludwig-Maximilians-Universität München
vorgelegt von
Sascha Glinka
aus Heilbronn
03.02.20051. Gutachter: Prof. Dr. Wolfgang Stephan
2. Gutachter: . John Parsch
Tag der mündlichen Prüfung: 03.05.2005SUMMARY
This thesis intends to detect evidence of Darwinian selection and ultimately identify
genes and substitutions that were involved in adaptation. The model organism
Drosophila melanogaster was chosen as the study object, since the availability of
the genome sequence and its evolutionary history allows us to investigate ancestral
and derived populations.
To identify the footprints of natural selection, the first objective was to locate genomic
regions subject to selection. Such footprints involve a reduction in genetic variation
along a recombining chromosome caused by a fixation of a beneficial mutation
(i.e., so-called “selective sweep”) in a population under study. Single nucleotide
polymorphisms of non-coding regions (i.e., 105 fragments) of the X chromosome in
a putatively ancestral population of D. melanogaster from Zimbabwe were surveyed
and compared to a derived European population in the first chapter. In contrast to
the European population, evidence of selection was weak in the African population,
but a strong signature of a population size expansion was observed. To examine
the impact of demography and selection more deeply, an analysis of an enlarged
DNA sequencing data set (i.e., 253 fragments) of the African population is presented
in chapter two. A clear signature of a recent size expansion was observed and the
time estimated of the expansion is 15,000 years before present, which was probably
caused by drastic climatic changes. The enlarged data set revealed, in addition, that
recombination is mutagenic in D. melanogaster.

In the second part of this thesis, candidate regions of selective sweeps detected
in the genome scan in both populations of D. melanogaster were investigated. In
chapter three, a more detailed analysis of the region comprising an observed local
reduction in variation in one X-linked fragment in the derived European population
revealed significant evidence of recent Darwinian selection. The target of selection
was attributed to three replacement sites leading to amino acid changes in two
predicted genes, CG1677 and CG2059. In contrast, a lower number of haplotypes
and a trend for low haplotype diversity suggesting the recent action of a selective
sweep was examined in chapter four in the ancestral D. melanogaster population.
An enlarged DNA sequencing data set revealed another feature unique to a selective
sweep, namely the decay in haplotype structure. The target of selection was localized
at the 5’ region of gene CG4661. In the third part of this thesis, the genetic variation of D. melanogaster populations from
Southeast Asia were examined to provide first insights into these derived
and the groundwork for future studies. Since no population genetic approach was
done in natural D. melanogaster populations from this region, inversions were used
as genetic markers. Other than a high frequency of the four common cosmopolitan
inversions, there were neither signs for genetic differentiation between populations
nor for natural selection. These findings can best be explained by a homogeneous
habitat and a joint history of these populations revealing the existence of a panmictic
population on Sundaland ~18,000 years ago. Table of Contents vii
Summary v
List of Abbreviations xi
Introduction 1
Part I: Genome Scan of Variation 11
Chapter 1 Demography and Natural Selection Have Shaped Genetic
Variation in Drosophila melanogaster: A Multi-locus Approach 13
1.1 Introduction 13
1.2 Materials and Methods 14
1.2.2 PCR Amplification and DNA Sequencing 14
1.2.3 Statistical Analysis 15
1.2.4 Recombination Rate 15
1.2.5 Demographic Modeling of the European Population 16
1.3 Results 17
1.3.1 Polymorphism Patterns in the African Population 18
1.3.2 Polymorphism Patterns in the European Population 21
1.3.3 Comparison of the African and European Populations 25
1.4 Discussion 28
1.4.1 Demography 28
1.4.2 Selection 29
Chapter 2 New Insights Into the Evolutionary History of
Drosophila melanogaster Using an Enlarged Multi-locus Data Set 31
2.1 Introduction 31
2.2 Materials and Methods 32
2.2.1 Population Samples 32
2.2.2 Cytological Analyses 33
2.2.3 PCR Amplification and DNA Sequencing 33
2.2.4 Statistical Analyses 33
2.2.5 Demographic Modeling of the African Population 34
2.3 Results 35
2.3.1 Chromosomal Analysis 35
2.3.2 Diversity and Divergence 36
2.3.3 Haplotype Structure and LD 38
2.3.4 Patterns of Polymorphism and Frequency Spectrum 39
2.3.5 Demographic Modeling of the African Population 39
2.4 Discussion 40
2.4.1 Diversity and Divergence 41
2.4.2 Demographic Expansion 42viii Table of Contents
Part II: Analysis of Candidate Sweep Regions 45
Chapter 3 Evidence of Gene Conversion Associated With a Selective
Sweep in Drosophila melanogaster 47
3.1 Introduction 47
3.2 Materials and Methods 49
3.2.1 Population Samples, PCR Amplification and DNA Sequencing 49
3.2.2 Sequence Analyses 50
3.2.3 Estimation of the Selective Sweep Parameters 50
3.2.4 Demographic Modeling of the European population 51
3.3 Results 51
3.3.1 Region of Reduced Level of Nucleotide Diversity 51
3.3.2 Departure from Standard Neutral Model 54
3.3.3 Estimation of Selective Sweep Parameters 54
3.3.4 Demographic Modeling of the European Population 55
3.3.5 Localization of Potential Beneficial Mutation 55
3.4 Discussion 56
3.4.1 Evidence for Selective Sweep 57
3.4.2 Gene Conversion Associated with Selective Sweep 58
Chapter 4 The Detection of Recent Positive Selection in Ancestral
Drosophila melanogaster from Haplotype Structure 61
4.1 Introduction 61
4.2 Materials and Methods 62
4.2.1 Population Samples, PCR Amplification and DNA Sequencing 62
4.2.2 Sequence Data Analyses 62
4.3 Results 64
4.4 Discussion 65
Part III: Genetic Variation of Derived Southeast Asian
Drosophila melanogaster 67
Chapter 5 High Frequencies of Common Cosmopolitan Inversions
in Southeast Asian Drosophila melanogaster 69
5.1 Introduction 69
5.2 Materials and Methods 70
5.3 Results 71
5.3.1 Chromosomal Analyses and Inversion Frequencies 71
5.3.2 Genetic Differentiation and Geographic Variation 72Table of Contents ix
5.4 Discussion 74
5.4.1 Inversions and Their Frequencies in Southeast Asia 74
5.4.2 Genetic Differentiation and Geographic Variation 75
5.4.3 Association between Inversions 77
Conclusion 79
Literature Cited 83
Appendix 97
Epilogue 139
Curriculum Vitae 141
List of Publications 143
Acknowledgements 145