| 1. |
- Bolivar, Paulina, et al.
(författare)
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Biased Inference of Selection Due to GC-Biased Gene Conversion and the Rate of Protein Evolution in Flycatchers When Accounting for It
- 2018
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Ingår i: Molecular biology and evolution. - : OXFORD UNIV PRESS. - 0737-4038 .- 1537-1719. ; 35:10, s. 2475-2486
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Bolivar, Paulina, et al.
(författare)
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GC-biased gene conversion conceals the prediction of the nearly neutral theory in avian genomes
- 2019
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Ingår i: Genome Biology. - : BMC. - 1465-6906 .- 1474-760X. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Bolívar, Paulina
(författare)
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Rates and patterns of molecular evolution in avian genomes
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 4. |
- Bolívar, Paulina, et al.
(författare)
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Recombination Rate Variation Modulates Gene Sequence Evolution Mainly via GC-Biased Gene Conversion, Not Hill-Robertson Interference, in an Avian System
- 2016
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 33:1, s. 216-227
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Boman, Jesper, et al.
(författare)
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Regulatory and evolutionary impact of DNA methylation in two songbird species and their naturally occurring F1 hybrids
- 2024
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Ingår i: BMC Biology. - : BioMed Central (BMC). - 1741-7007. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Regulation of transcription by DNA methylation in 5'-CpG-3' context is a widespread mechanism allowing differential expression of genetically identical cells to persist throughout development. Consequently, differences in DNA methylation can reinforce variation in gene expression among cells, tissues, populations, and species. Despite a surge in studies on DNA methylation, we know little about the importance of DNA methylation in population differentiation and speciation. Here we investigate the regulatory and evolutionary impact of DNA methylation in five tissues of two Ficedula flycatcher species and their naturally occurring F-1 hybrids.Results: We show that the density of CpG in the promoters of genes determines the strength of the association between DNA methylation and gene expression. The impact of DNA methylation on gene expression varies among tissues with the brain showing unique patterns. Differentially expressed genes between parental species are predicted by genetic and methylation differentiation in CpG-rich promoters. However, both these factors fail to predict hybrid misexpression suggesting that promoter mismethylation is not a main determinant of hybrid misexpression in Ficedula flycatchers. Using allele-specific methylation estimates in hybrids, we also determine the genome-wide contribution of cis- and trans effects in DNA methylation differentiation. These distinct mechanisms are roughly balanced in all tissues except the brain, where trans differences predominate.Conclusions: Overall, this study provides insight on the regulatory and evolutionary impact of DNA methylation in songbirds.
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| 6. |
- Boman, Jesper, et al.
(författare)
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The Effects of GC-Biased Gene Conversion on Patterns of Genetic Diversity among and across Butterfly Genomes
- 2021
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Ingår i: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Recombination reshuffles the alleles of a population through crossover and gene conversion. These mechanisms have considerable consequences on the evolution and maintenance of genetic diversity. Crossover, for example, can increase genetic diversity by breaking the linkage between selected and nearby neutral variants. Bias in favor of G or C alleles during gene conversion may instead promote the fixation of one allele over the other, thus decreasing diversity. Mutation bias from G or C to A and T opposes GC-biased gene conversion (gBGC). Less recognized is that these two processes may-when balanced-promote genetic diversity. Here, we investigate how gBGC and mutation bias shape genetic diversity patterns in wood white butterflies (Leptidea sp.). This constitutes the first in-depth investigation of gBGC in butterflies. Using 60 resequenced genomes from six populations of three species, we find substantial variation in the strength of gBGC across lineages. When modeling the balance of gBGC and mutation bias and comparing analytical results with empirical data, we reject gBGC as the main determinant of genetic diversity in these butterfly species. As alternatives, we consider linked selection and GC content. We find evidence that high values of both reduce diversity. We also show that the joint effects of gBGC and mutation bias can give rise to a diversity pattern which resembles the signature of linked selection. Consequently, gBGC should be considered when interpreting the effects of linked selection on levels of genetic diversity.
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| 7. |
- Burri, Reto, et al.
(författare)
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Linked selection and recombination rate variation drive the evolution of the genomic landscape of differentiation across the speciation continuum of Ficedula flycatchers
- 2015
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:11, s. 1656-1665
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Tidskriftsartikel (refereegranskat)abstract
- Speciation is a continuous process during which genetic changes gradually accumulate in the genomes of diverging species. Recent studies have documented highly heterogeneous differentiation landscapes, with distinct regions of elevated differentiation ("differentiation islands") widespread across genomes. However, it remains unclear which processes drive the evolution of differentiation islands; how the differentiation landscape evolves as speciation advances; and ultimately, how differentiation islands are related to speciation. Here, we addressed these questions based on population genetic analyses of 200 resequenced genomes from 10 populations of four Ficedula flycatcher sister species. We show that a heterogeneous differentiation landscape starts emerging among populations within species, and differentiation islands evolve recurrently in the very same genomic regions among independent lineages. Contrary to expectations from models that interpret differentiation islands as genomic regions involved in reproductive isolation that are shielded from gene flow, patterns of sequence divergence (d(XY) relative node depth) do not support a major role of gene flow in the evolution of the differentiation landscape in these species. Instead, as predicted by models of linked selection, genome-wide variation in diversity and differentiation can be explained by variation in recombination rate and the density of targets for selection. We thus conclude that the heterogeneous landscape of differentiation in Ficedula flycatchers evolves mainly as the result of background selection and selective sweeps in genomic regions of low recombination. Our results emphasize the necessity of incorporating linked selection as a null model to identify genome regions involved in adaptation and speciation.
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| 8. |
- Chase, Madeline A., et al.
(författare)
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Positive selection plays a major role in shaping signatures of differentiation across the genomic landscape of two independent Ficedula flycatcher species pairs
- 2021
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Ingår i: Evolution. - : John Wiley & Sons. - 0014-3820 .- 1558-5646. ; 75:9, s. 2179-2196
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Tidskriftsartikel (refereegranskat)abstract
- A current debate within population genomics surrounds the relevance of patterns of genomic differentiation between closely related species for our understanding of adaptation and speciation. Mounting evidence across many taxa suggests that the same genomic regions repeatedly develop elevated differentiation in independent species pairs. These regions often coincide with high gene density and/or low recombination, leading to the hypothesis that the genomic differentiation landscape mostly reflects a history of background selection, and reveals little about adaptation or speciation. A comparative genomics approach with multiple independent species pairs at a timescale where gene flow and ILS are negligible permits investigating whether different evolutionary processes are responsible for generating lineage-specific versus shared patterns of species differentiation. We use whole-genome resequencing data of 195 individuals from four Ficedula flycatcher species comprising two independent species pairs: collared and pied flycatchers, and red-breasted and taiga flycatchers. We found that both shared and lineage-specific FST peaks could partially be explained by selective sweeps, with recurrent selection likely to underlie shared signatures of selection, whereas indirect evidence supports a role of recombination landscape evolution in driving lineage-specific signatures of selection. This work therefore provides evidence for an interplay of positive selection and recombination to genomic landscape evolution.
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| 9. |
- Chase, Madeline, et al.
(författare)
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Evidence that genetic drift not adaptation drives fast-Z and large-Z effects in Ficedula flycatchers
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The sex chromosomes have been hypothesized to play a key role in driving adaptation and speciation across many taxa. The reason for this is thought to be the hemizygosity of the heteromorphic part of sex chromosomes in the heterogametic sex, which exposes recessive mutations to natural and sexual selection. The exposure of recessive beneficial mutations increases their rate of fixation on the sex chromosomes, which results in a faster rate of evolution. In addition, genetic incompatibilities between sex-linked loci are exposed faster in the genomic background of hybrids of divergent species, which makes sex chromosomes contribute disproportionately to reproductive isolation. However, in birds, which show a Z/W sex determination system, the disproportionate role of the Z-chromosome in adaptation and reproductive isolation is still debated. Instead, genetic drift has been proposed as the main driver of the so-called fast-Z and large-Z effects in birds. Here, we address this question in Ficedula flycatchers based on population resequencing data of six flycatcher species. Our results provide evidence for both the fast-Z and large-Z effects in Ficedula flycatchers and that these two phenomena are driven by genetic drift rather than positive selection. Genomic scans of selective sweeps and fixed differences in fact suggest a reduced action of positive selection on the Z-chromosome. We propose that the observed reduction in the efficacy of purifying selection on the Z-chromosome helps to establish genetic incompatibilities between Z-linked and autosomal loci, which could result in pronounced selective sweep signatures for compensatory mutations on the autosomes.
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| 10. |
- Chase, Madeline
(författare)
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Speciation genomics in Ficedula flycatchers
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Understanding what evolutionary processes have shaped patterns of genomic differentiation between species is a major aim of speciation genomics. However, disentangling the role of different processes that generate similar patterns remains a substantial challenge. Within this thesis, I aimed to infer the action of different evolutionary processes through population-level genome re-sequencing of closely related species. I explored how processes such as recombination, natural selection, and genetic drift interact to shape the genomic differentiation landscape among multiple species of Ficedula flycatcher. Collared flycatcher and pied flycatcher are a pair of closely related species, which hybridize in regions of secondary contact. Reproductive isolation is strong and hybrids appear to be sterile. I compared the differentiation landscape between collared and pied flycatchers with a more distantly related species pair, the red-breasted and taiga flycatchers. This comparison revealed elevated regions of genomic differentiation shared between the two pairs, i.e. shared differentiation peaks, and those unique to a single pair, i.e. lineage-specific differentiation peaks. Since the two species pairs share a negligible portion of genetic variation, shared patterns in the differentiation landscape should be driven and maintained by conserved processes, while lineage-specific patterns should be driven by lineage-specific changes in relevant evolutionary processes. Selective sweep scans suggested that both shared and lineage-specific peaks can result from adaptive evolution and that lineage-specific adaptation is not a sufficient determinant of lineage-specific peaks. Instead, lineage-specific differentiation peaks appeared to be driven by evolutionary changes in the recombination landscape, the dynamics of which had strong impacts on the detection of signatures of linked selection. I also found that adaptation did not play a prominent role on Z-chromosome differentiation. Both the fast-Z and large-Z effects were apparent within the flycatchers but appeared to be primarily driven by the increased role of genetic drift on the Z-chromosome due to its reduced effective population size compared to the autosomes. I hypothesized that the increased impact of genetic drift could speed up the buildup of genetic incompatibilities of Z-linked and autosomal loci and contribute to reproductive isolation. Finally, using long-read and HiC sequencing data, I generated high-quality reference genomes for the collared flycatcher and pied flycatcher, and provided a first glimpse of the role of structural variation in speciation. I observed an increased prevalence of inversions and translocations on the sex chromosomes and in differentiation peaks. Structural rearrangements may therefore represent an important source of genomic variation contributing to species divergence.
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