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. |
- 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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6. |
- 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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7. |
- Dutoit, Ludovic, et al.
(författare)
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Covariation in levels of nucleotide diversity in homologous regions of the avian genome long after completion of lineage sorting
- 2017
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : ROYAL SOC. - 0962-8452 .- 1471-2954. ; 284:1849
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Tidskriftsartikel (refereegranskat)abstract
- Closely related species may show similar levels of genetic diversity in homologous regions of the genome owing to shared ancestral variation still segregating in the extant species. However, after completion of lineage sorting, such covariation is not necessarily expected. On the other hand, if the processes that govern genetic diversity are conserved, diversity may potentially covary even among distantly related species. We mapped regions of conserved synteny between the genomes of two divergent bird speciescollared flycatcher and hooded crow-and identified more than 600 Mb of homologous regions (66% of the genome). From analyses of whole-genome resequencing data in large population samples of both species we found nucleotide diversity in 200 kb windows to be well correlated (Spearman's rho = 0.407). The correlation remained highly similar after excluding coding sequences. To explain this covariation, we suggest that a stable avian karyotype and a conserved landscape of recombination rate variation render the diversity-reducing effects of linked selection similar in divergent bird lineages. Principal component regression analysis of several potential explanatory variables driving heterogeneity in flycatcher diversity levels revealed the strongest effects from recombination rate variation and density of coding sequence targets for selection, consistent with linked selection. It is also possible that a stable karyotype is associated with a conserved genomic mutation environment contributing to covariation in diversity levels between lineages. Our observations imply that genetic diversity is to some extent predictable.
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8. |
- Dutoit, Ludovic, et al.
(författare)
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Genomic distribution and estimation of nucleotide diversity in natural populations : perspectives from the collared flycatcher (Ficedula albicollis) genome
- 2017
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 17:4, s. 586-597
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Tidskriftsartikel (refereegranskat)abstract
- Properly estimating genetic diversity in populations of nonmodel species requires a basic understanding of how diversity is distributed across the genome and among individuals. To this end, we analysed whole-genome resequencing data from 20 collared flycatchers (genome size approximate to 1.1 Gb; 10.13 million single nucleotide polymorphisms detected). Genomewide nucleotide diversity was almost identical among individuals (mean = 0.00394, range = 0.00384-0.00401), but diversity levels varied extensively across the genome (95% confidence interval for 200-kb windows = 0.0013-0.0053). Diversity was related to selective constraint such that in comparison with intergenic DNA, diversity at fourfold degenerate sites was reduced to 85%, 3' UTRs to 82%, 5' UTRs to 70% and nondegenerate sites to 12%. There was a strong positive correlation between diversity and chromosome size, probably driven by a higher density of targets for selection on smaller chromosomes increasing the diversity-reducing effect of linked selection. Simulations exploring the ability of sequence data from a small number of genetic markers to capture the observed diversity clearly demonstrated that diversity estimation from finite sampling of such data is bound to be associated with large confidence intervals. Nevertheless, we show that precision in diversity estimation in large out-bred population benefits from increasing the number of loci rather than the number of individuals. Simulations mimicking RAD sequencing showed that this approach gives accurate estimates of genomewide diversity. Based on the patterns of observed diversity and the performed simulations, we provide broad recommendations for how genetic diversity should be estimated in natural populations.
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9. |
- Dutoit, Ludovic, et al.
(författare)
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Sex-biased gene expression, sexual antagonism and levels of genetic diversity in the collared flycatcher (Ficedula albicollis) genome
- 2018
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 27:18, s. 3572-3581
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Theoretical work suggests that sexual conflict should promote the maintenance of genetic diversity by the opposing directions of selection on sexually antagonistic mutations in males and females. This prediction, so far not been empirically tested on a genome-wide scale, could potentially contribute towards genomic heterogeneity in levels of genetic diversity. We used large-scale population genomic and transcriptomic data from the collared flycatcher (Ficedula albicollis) to analyse how sex-biased gene expression – one outcome of sexual conflict – relates to genetic variability. Here, we demonstrate that the extent of sex-biased gene expression of both male-biased and female-biased genes is significantly correlated with levels of nucleotide diversity in gene sequences and that this correlation extends to the overall levels of genomic diversity. We find evidence for balancing selection in sex-biased genes, suggesting that sex-biased gene expression could be seen as a component counteracting the diversity-reducing effects of linked positive and purifying selection. The observation of significant genetic differentiation between males and females for male-biased genes indicates ongoing sexual conflict and sex-specific viability selection, potentially driven by sexual selection. Our results thus provide a new perspective on the long-standing question in evolutionary biology of how genomes can remain so genetically variable in face of strong natural and sexual selection.
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10. |
- Kawakami, Takeshi, et al.
(författare)
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A high-density linkage map enables a second-generation collared flycatcher genome assembly and reveals the patterns of avian recombination rate variation and chromosomal evolution
- 2014
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 23:16, s. 4035-4058
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Forskningsöversikt (refereegranskat)abstract
- Detailed linkage and recombination rate maps are necessary to use the full potential of genome sequencing and population genomic analyses. We used a custom collared flycatcher 50K SNP array to develop a high-density linkage map with 37262 markers assigned to 34 linkage groups in 33 autosomes and the Z chromosome. The best-order map contained 4215 markers, with a total distance of 3132cM and a mean genetic distance between markers of 0.12cM. Facilitated by the array being designed to include markers from most scaffolds, we obtained a second-generation assembly of the flycatcher genome that approaches full chromosome sequences (N50 super-scaffold size 20.2Mb and with 1.042Gb (of 1.116Gb) anchored to and mostly ordered and oriented along chromosomes). We found that flycatcher and zebra finch chromosomes are entirely syntenic but that inversions at mean rates of 1.5-2.0 event (6.6-7.5Mb) per My have changed the organization within chromosomes, rates high enough for inversions to potentially have been involved with many speciation events during avian evolution. The mean recombination rate was 3.1cM/Mb and correlated closely with chromosome size, from 2cM/Mb for chromosomes >100Mb to >10cM/Mb for chromosomes <10Mb. This size dependence seemed entirely due to an obligate recombination event per chromosome; if 50cM was subtracted from the genetic lengths of chromosomes, the rate per physical unit DNA was constant across chromosomes. Flycatcher recombination rate showed similar variation along chromosomes as chicken but lacked the large interior recombination deserts characteristic of zebra finch chromosomes.
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