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Rates and patterns of molecular evolution in avian genomes
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Evolution is the change in inherited characteristics of a population through subsequent generations. The interplay of several evolutionary mechanisms determines the rate at which this change occurs. In short, genetic variation is generated though mutation, and the fate of these mutations in a population is determined mainly by the combined effect of genetic drift, natural selection and recombination. Elucidating the relative impact of these mechanisms is complex; making it a long-standing question in evolutionary biology. In this thesis, I focus on disentangling the relative roles of these evolutionary mechanisms and genetic factors in determining rates and patterns of evolution at the molecular level, by studying variation in the DNA sequence of multiple avian species, and in particular the collared flycatcher (Ficedula albicollis). Specifically, I aim to further our understanding regarding the impact of recombination rate on genome evolution, through its interaction with the efficacy of selection and through the process of GC-biased gene conversion (gBGC), which has been poorly characterized in birds. I demonstrate that gBGC has a pervasive effect on the genome of the collared flycatcher and other avian species, as it increases the substitution rate and affects interpretations of the impact of natural selection and adaptation. Interestingly, its effect is even stronger in neutrally evolving sites compared to sites evolving under selection. After accounting for gBGC, I disentangle the true impact of natural selection versus non-adaptive processes in determining rates of molecular evolution in the collared flycatcher genome, shedding light on the process of adaptation. Finally, I demonstrate the significant role of recombination through its impact on linked selection, along with mutation rate differences, in determining relative levels of genetic diversity and their relationship to the fast-Z effect across the avian phylogeny. This thesis urges future studies to account for the effect of recombination before interpreting patterns of selection in sequence evolution.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 51
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1800
Keywords [en]
Molecular evolution, recombination, GC-biased gene conversion, Hill-Robertson interference, effective population size, dN/dS, distribution of fitness effects, avian genomes, collared flycatcher, sex chromosomes
National Category
Evolutionary Biology Genetics
Research subject
Biology with specialization in Evolutionary Genetics
Identifiers
URN: urn:nbn:se:uu:diva-381373ISBN: 978-91-513-0637-7 (print)OAI: oai:DiVA.org:uu-381373DiVA, id: diva2:1303149
Public defence
2019-06-11, Evolutionary Biology Center, Norbyvägen 14, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2019-05-20 Created: 2019-04-09 Last updated: 2019-06-17
List of papers
1. Recombination Rate Variation Modulates Gene Sequence Evolution Mainly via GC-Biased Gene Conversion, Not Hill-Robertson Interference, in an Avian System
Open this publication in new window or tab >>Recombination Rate Variation Modulates Gene Sequence Evolution Mainly via GC-Biased Gene Conversion, Not Hill-Robertson Interference, in an Avian System
2016 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 33, no 1, p. 216-227Article in journal (Refereed) Published
Abstract [en]

The ratio of nonsynonymous to synonymous substitution rates (ω) is often used to measure the strength of natural selection. However, ω may be influenced by linkage among different targets of selection, that is, Hill-Robertson interference (HRI), which reduces the efficacy of selection. Recombination modulates the extent of HRI but may also affect ω by means of GC-biased gene conversion (gBGC), a process leading to a preferential fixation of G:C ("strong," S) over A:T ("weak," W) alleles. As HRI and gBGC can have opposing effects on ω, it is essential to understand their relative impact to make proper inferences of ω. We used a model that separately estimated S-to-S, S-to-W, W-to-S, and W-to-W substitution rates in 8,423 avian genes in the Ficedula flycatcher lineage. We found that the W-to-S substitution rate was positively, and the S-to-W rate negatively, correlated with recombination rate, in accordance with gBGC but not predicted by HRI. The W-to-S rate further showed the strongest impact on both dN and dS. However, since the effects were stronger at 4-fold than at 0-fold degenerated sites, likely because the GC content of these sites is farther away from its equilibrium, ω slightly decreases with increasing recombination rate, which could falsely be interpreted as a consequence of HRI. We corroborated this hypothesis analytically and demonstrate that under particular conditions, ω can decrease with increasing recombination rate. Analyses of the site-frequency spectrum showed that W-to-S mutations were skewed toward high, and S-to-W mutations toward low, frequencies, consistent with a prevalent gBGC-driven fixation bias.

Keywords
gBGC; Hill-Robertson interference; d(N)/d(S); divergence; diversity; rate of molecular evolution
National Category
Evolutionary Biology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-280275 (URN)10.1093/molbev/msv214 (DOI)000369992600017 ()26446902 (PubMedID)
Funder
Swedish Research Council, 2010-5650Swedish Research Council, 2013-8271EU, European Research Council, AdG 249976Knut and Alice Wallenberg Foundation
Available from: 2016-03-09 Created: 2016-03-09 Last updated: 2019-04-09Bibliographically approved
2. Biased Inference of Selection Due to GC-Biased Gene Conversion and the Rate of Protein Evolution in Flycatchers When Accounting for It
Open this publication in new window or tab >>Biased Inference of Selection Due to GC-Biased Gene Conversion and the Rate of Protein Evolution in Flycatchers When Accounting for It
Show others...
2018 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 35, no 10, p. 2475-2486Article in journal (Refereed) Published
Abstract [en]

The rate of recombination impacts on rates of protein evolution for at least two reasons: it affects the efficacy of selection due to linkage and influences sequence evolution through the process of GC-biased gene conversion (gBGC). We studied how recombination, via gBGC, affects inferences of selection in gene sequences using comparative genomic and population genomic data from the collared flycatcher (Ficedula albicollis). We separately analyzed different mutation categories ("strong"-to-"weak" "weak-to-strong," and GC-conservative changes) and found that gBGC impacts on the distribution of fitness effects of new mutations, and leads to that the rate of adaptive evolution and the proportion of adaptive mutations among nonsynonymous substitutions are underestimated by 22-33%. It also biases inferences of demographic history based on the site frequency spectrum. In light of this impact, we suggest that inferences of selection (and demography) in lineages with pronounced gBGC should be based on GC-conservative changes only. Doing so, we estimate that 10% of nonsynonymous mutations are effectively neutral and that 27% of nonsynonymous substitutions have been fixed by positive selection in the flycatcher lineage. We also find that gene expression level, sex-bias in expression, and the number of protein-protein interactions, but not Hill-Robertson interference (HRI), are strong determinants of selective constraint and rate of adaptation of collared flycatcher genes. This study therefore illustrates the importance of disentangling the effects of different evolutionary forces and genetic factors in interpretation of sequence data, and from that infer the role of natural selection in DNA sequence evolution.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
d(N)/d(S), distribution of fitness effects, GC-biased gene conversion, gene expression, Hill-Robertson interference
National Category
Evolutionary Biology Genetics
Identifiers
urn:nbn:se:uu:diva-372675 (URN)10.1093/molbev/msy149 (DOI)000452566800011 ()30085180 (PubMedID)
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-04-09Bibliographically approved
3. GC-biased gene conversion conceals the prediction of the nearly neutral theory in avian genomes
Open this publication in new window or tab >>GC-biased gene conversion conceals the prediction of the nearly neutral theory in avian genomes
Show others...
2019 (English)In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 20, article id 5Article in journal (Refereed) Published
Abstract [en]

Background: The nearly neutral theory of molecular evolution predicts that the efficacy of natural selection increases with the effective population size. This prediction has been verified by independent observations in diverse taxa, which show that life-history traits are strongly correlated with measures of the efficacy of selection, such as the d(N)/d(S) ratio. Surprisingly, avian taxa are an exception to this theory because correlations between life-history traits and d(N)/d(S) are apparently absent. Here we explore the role of GC-biased gene conversion on estimates of substitution rates as a potential driver of these unexpected observations.

Results: We analyze the relationship between d(N)/d(S) estimated from alignments of 47 avian genomes and several proxies for effective population size. To distinguish the impact of GC-biased gene conversion from selection, we use an approach that accounts for non-stationary base composition and estimate d(N)/d(S) separately for changes affected or unaffected by GC-biased gene conversion. This analysis shows that the impact of GC-biased gene conversion on substitution rates can explain the lack of correlations between life-history traits and d(N)/d(S). Strong correlations between life-history traits and d(N)/d(S) are recovered after accounting for GC-biased gene conversion. The correlations are robust to variation in base composition and genomic location.

Conclusions: Our study shows that gene sequence evolution across a wide range of avian lineages meets the prediction of the nearly neutral theory,the efficacy of selection increases with effective population size. Moreover, our study illustrates that accounting for GC-biased gene conversion is important to correctly estimate the strength of selection.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Nearly neutral theory, Life-history traits, d(N), d(S), GC-biased gene conversion, Base composition, Avian genomes
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-375222 (URN)10.1186/s13059-018-1613-z (DOI)000455139400002 ()30616647 (PubMedID)
Funder
Swedish Research Council, 2013-8271Knut and Alice Wallenberg Foundation, 2014/0044
Available from: 2019-01-30 Created: 2019-01-30 Last updated: 2019-04-09Bibliographically approved
4. Variation in the Z Chromosome to Autosomes Ratio of Genetic Diversity across Birds and its Relationship to the Fast-Z effect
Open this publication in new window or tab >>Variation in the Z Chromosome to Autosomes Ratio of Genetic Diversity across Birds and its Relationship to the Fast-Z effect
(English)Manuscript (preprint) (Other academic)
Keywords
sex chromosomes, genetic diversity, Fast-Z evolution, genetic drift, selection
National Category
Evolutionary Biology
Research subject
Biology with specialization in Evolutionary Genetics
Identifiers
urn:nbn:se:uu:diva-380263 (URN)
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-04-09

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