| 1. |
- Bolivar, Paulina, et al.
(författare)
-
Biased Inference of Selection Due to GC-Biased Gene Conversion and the Rate of Protein Evolution in Flycatchers When Accounting for It
- 2018
-
Ingår i: Molecular biology and evolution. - : OXFORD UNIV PRESS. - 0737-4038 .- 1537-1719. ; 35:10, s. 2475-2486
-
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.
|
|
| 2. |
- Bolivar, Paulina, et al.
(författare)
-
GC-biased gene conversion conceals the prediction of the nearly neutral theory in avian genomes
- 2019
-
Ingår i: Genome Biology. - : BMC. - 1465-6906 .- 1474-760X. ; 20
-
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.
|
|
| 3. |
- Bolívar, Paulina
(författare)
-
Rates and patterns of molecular evolution in avian genomes
- 2019
-
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.
|
|
| 4. |
- Bolívar, Paulina, et al.
(författare)
-
Recombination Rate Variation Modulates Gene Sequence Evolution Mainly via GC-Biased Gene Conversion, Not Hill-Robertson Interference, in an Avian System
- 2016
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 33:1, s. 216-227
-
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.
|
|
| 5. |
- Boman, Jesper, et al.
(författare)
-
Regulatory and evolutionary impact of DNA methylation in two songbird species and their naturally occurring F1 hybrids
- 2024
-
Ingår i: BMC Biology. - : BioMed Central (BMC). - 1741-7007. ; 22:1
-
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.
|
|
| 6. |
- Boman, Jesper, et al.
(författare)
-
The Effects of GC-Biased Gene Conversion on Patterns of Genetic Diversity among and across Butterfly Genomes
- 2021
-
Ingår i: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 13:5
-
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.
|
|
| 7. |
- Burri, Reto, et al.
(författare)
-
Linked selection and recombination rate variation drive the evolution of the genomic landscape of differentiation across the speciation continuum of Ficedula flycatchers
- 2015
-
Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:11, s. 1656-1665
-
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.
|
|
| 8. |
- Chase, Madeline A., et al.
(författare)
-
Positive selection plays a major role in shaping signatures of differentiation across the genomic landscape of two independent Ficedula flycatcher species pairs
- 2021
-
Ingår i: Evolution. - : John Wiley & Sons. - 0014-3820 .- 1558-5646. ; 75:9, s. 2179-2196
-
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.
|
|
| 9. |
- Chase, Madeline, et al.
(författare)
-
Evidence that genetic drift not adaptation drives fast-Z and large-Z effects in Ficedula flycatchers
-
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.
|
|
| 10. |
- Chase, Madeline
(författare)
-
Speciation genomics in Ficedula flycatchers
- 2023
-
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.
|
|
| 11. |
- Chase, Madeline, et al.
(författare)
-
The combination of HiFi and HiC sequencing technologies enables the investigation of structural variants in speciation of Ficedula flycatchers
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Structural variants, typically defined as mutations affecting more than 50bp, have been shown to encompass a significant portion of the genome and can have large phenotypic effects. Additionally, increasing empirical evidence demonstrates that structural variants may play a substantial role in speciation, which could previously have been overlooked because of difficulties in identifying them with short-read data. However, with the increased availability of long-read sequencing technology we are now equipped better than ever to address this limitation and study the contribution of different types of structural variants to genetic variation within and genetic differentiation between closely related species. Here, we follow this approach and combine PacBio HiFi and HiC sequencing for two closely related passerine birds, the collared flycatcher and the pied flycatcher. This enables us to generate a chromosome-level genome assembly for both species, and identify structural variants between the two species. Based on population-level HiFi sequencing for both species, we then investigate patterns of single nucleotide diversity and differentiation within and between species and their association with different types of structural variation. We find widespread structural variation between the two species, where both the sex chromosomes show a disproportionate number of structural variants, which may help explain the suspected role of the Z-chromosome in contributing to genetic incompatibilities. We also find that genomic differentiation peaks are enriched in both translocations and inversions, which supports a mechanistic role of structural variation in population differentiation and speciation.
|
|
| 12. |
- Chase, Madeline, et al.
(författare)
-
The role of recombination dynamics in shaping signatures of direct and indirect selection across the Ficedula flycatcher genome
- 2024
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Recombination is a central evolutionary process that reshuffles combinations of alleles along chromosomes, and consequently is expected to influence the efficacy of direct selection via Hill-Robertson interference. Additionally, the indirect effects of selection on neutral genetic diversity are expected to show a negative relationship with recombination rate, as background selection and genetic hitchhiking are stronger when recombination rate is low. However, owing to the limited availability of recombination rate estimates across divergent species, less is known about the impact of evolutionary changes in recombination rate on genomic signatures of selection. To address this question, we estimate recombination rate in two Ficedula flycatcher species, the taiga flycatcher (F. albicilla) and collared flycatcher (F. albicollis). We show that recombination rate is strongly correlated with signatures of indirect selection, and that evolutionary changes in recombination rate between species have observable impacts on this relationship. Conversely, signatures of direct selection on coding sequences show little to no relationship with recombination rate, even when restricted to genes where recombination rate is conserved between species. Thus, using measures of indirect and direct selection that bridge micro- and macro-evolutionary timescales, we demonstrate that the role of recombination rate and its dynamics varies for different signatures of selection.
|
|
| 13. |
- Chase, Madeline, et al.
(författare)
-
The role of recombination dynamics in shaping signatures of direct and indirect selection across the Ficedula flycatcher genome
- 2024
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : ROYAL SOC. - 0962-8452 .- 1471-2954. ; 291:2015
-
Tidskriftsartikel (refereegranskat)abstract
- Recombination is a central evolutionary process that reshuffles combinations of alleles along chromosomes, and consequently is expected to influence the efficacy of direct selection via Hill-Robertson interference. Additionally, the indirect effects of selection on neutral genetic diversity are expected to show a negative relationship with recombination rate, as background selection and genetic hitchhiking are stronger when recombination rate is low. However, owing to the limited availability of recombination rate estimates across divergent species, the impact of evolutionary changes in recombination rate on genomic signatures of selection remains largely unexplored. To address this question, we estimate recombination rate in two Ficedula flycatcher species, the taiga flycatcher (Ficedula albicilla) and collared flycatcher (Ficedula albicollis). We show that recombination rate is strongly correlated with signatures of indirect selection, and that evolutionary changes in recombination rate between species have observable impacts on this relationship. Conversely, signatures of direct selection on coding sequences show little to no relationship with recombination rate, even when restricted to genes where recombination rate is conserved between species. Thus, using measures of indirect and direct selection that bridge micro- and macro-evolutionary timescales, we demonstrate that the role of recombination rate and its dynamics varies for different signatures of selection.
|
|
| 14. |
- Dutoit, Ludovic, et al.
(författare)
-
Covariation in levels of nucleotide diversity in homologous regions of the avian genome long after completion of lineage sorting
- 2017
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : ROYAL SOC. - 0962-8452 .- 1471-2954. ; 284:1849
-
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.
|
|
| 15. |
- Dutoit, Ludovic, et al.
(författare)
-
Genomic distribution and estimation of nucleotide diversity in natural populations : perspectives from the collared flycatcher (Ficedula albicollis) genome
- 2017
-
Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 17:4, s. 586-597
-
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.
|
|
| 16. |
- Dutoit, Ludovic, et al.
(författare)
-
Sex-biased gene expression, sexual antagonism and levels of genetic diversity in the collared flycatcher (Ficedula albicollis) genome
- 2018
-
Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 27:18, s. 3572-3581
-
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.
|
|
| 17. |
- Hart, Michael W., et al.
(författare)
-
Positive selection on human gamete-recognition genes
- 2018
-
Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Coevolution of genes that encode interacting proteins expressed on the surfaces of sperm and eggs can lead to variation in reproductive compatibility between mates and reproductive isolation between members of different species. Previous studies in mice and other mammals have focused in particular on evidence for positive or diversifying selection that shapes the evolution of genes that encode sperm-binding proteins expressed in the egg coat or zona pellucida (ZP). By fitting phylogenetic models of codon evolution to data from the 1000 Genomes Project, we identified candidate sites evolving under diversifying selection in the human genes ZP3 and ZP2. We also identified one candidate site under positive selection in C4BPA, which encodes a repetitive protein similar to the mouse protein ZP3R that is expressed in the sperm head and binds to the ZP at fertilization. Results from several additional analyses that applied population genetic models to the same data were consistent with the hypothesis of selection on those candidate sites leading to coevolution of sperm- and egg-expressed genes. By contrast, we found no candidate sites under selection in a fourth gene (ZP1) that encodes an egg coat structural protein not directly involved in sperm binding. Finally, we found that two of the candidate sites (in C4BPA and ZP2) were correlated with variation in family size and birth rate among Hutterite couples, and those two candidate sites were also in linkage disequilibrium in the same Hutterite study population. All of these lines of evidence are consistent with predictions from a previously proposed hypothesis of balancing selection on epistatic interactions between C4BPA and ZP3 at fertilization that lead to the evolution of co-adapted allele pairs. Such patterns also suggest specific molecular traits that may be associated with both natural reproductive variation and clinical infertility.
|
|
| 18. |
- Hart, M. W., et al.
(författare)
-
Selection on coevolving human gamete recognition genes
- 2016
-
Ingår i: Integrative and Comparative Biology. - Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. Arizona State Univ, Tempe, AZ 85287 USA. Univ Chicago, Chicago, IL 60637 USA. Uppsala Univ, Uppsala, Sweden.. - 1540-7063 .- 1557-7023. ; 56, s. E84-E84
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 19. |
- Kaj, Ingemar, et al.
(författare)
-
The non-equilibrium allele frequency spectrum in a Poisson random field framework
- 2016
-
Ingår i: Theoretical Population Biology. - : Elsevier BV. - 0040-5809 .- 1096-0325. ; 111, s. 51-64
-
Tidskriftsartikel (refereegranskat)abstract
- In population genetic studies, the allele frequency spectrum (AFS) efficiently summarizes genome-wide polymorphism data and shapes a variety of allele frequency-based summary statistics. While existing theory typically features equilibrium conditions, emerging methodology requires an analytical understanding of the build-up of the allele frequencies over time. In this work, we use the framework of Poisson random fields to derive new representations of the non-equilibrium AFS for the case of a Wright-Fisher population model with selection. In our approach, the AFS is a scaling-limit of the expectation of a Poisson stochastic integral and the representation of the non-equilibrium AFS arises in terms of a fixation time probability distribution. The known duality between the Wright-Fisher diffusion process and a birth and death process generalizing Kingman's coalescent yields an additional representation. The results carry over to the setting of a random sample drawn from the population and provide the non-equilibrium behavior of sample statistics. Our findings are consistent with and extend a previous approach where the non-equilibrium AFS solves a partial differential forward equation with a non-traditional boundary condition. Moreover, we provide a bridge to previous coalescent-based work, and hence tie several frameworks together. Since frequency-based summary statistics are widely used in population genetics, for example, to identify candidate loci of adaptive evolution, to infer the demographic history of a population, or to improve our understanding of the underlying mechanics of speciation events, the presented results are potentially useful for a broad range of topics.
|
|
| 20. |
- Kawakami, Takeshi, et al.
(författare)
-
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
-
Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 23:16, s. 4035-4058
-
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.
|
|
| 21. |
- Kawakami, Takeshi, et al.
(författare)
-
Whole-genome patterns of linkage disequilibrium across flycatcher populations clarify the causes and consequences of fine-scale recombination rate variation in birds
- 2017
-
Ingår i: Molecular Ecology. - : WILEY. - 0962-1083 .- 1365-294X. ; 26:16, s. 4158-4172
-
Tidskriftsartikel (refereegranskat)abstract
- Recombination rate is heterogeneous across the genome of various species and so are genetic diversity and differentiation as a consequence of linked selection. However, we still lack a clear picture of the underlying mechanisms for regulating recombination. Here we estimated fine-scale population recombination rate based on the patterns of linkage disequilibrium across the genomes of multiple populations of two closely related flycatcher species (Ficedula albicollis and F. hypoleuca). This revealed an overall conservation of the recombination landscape between these species at the scale of 200 kb, but we also identified differences in the local rate of recombination despite their recent divergence (<1 million years). Genetic diversity and differentiation were associated with recombination rate in a lineage-specific manner, indicating differences in the extent of linked selection between species. We detected 400-3,085 recombination hotspots per population. Location of hotspots was conserved between species, but the intensity of hotspot activity varied between species. Recombination hotspots were primarily associated with CpG islands (CGIs), regardless of whether CGIs were at promoter regions or away from genes. Recombination hotspots were also associated with specific transposable elements (TEs), but this association appears indirect due to shared preferences of the transposition machinery and the recombination machinery for accessible open chromatin regions. Our results suggest that CGIs are a major determinant of the localization of recombination hotspots, and we propose that both the distribution of TEs and fine-scale variation in recombination rate may be associated with the evolution of the epigenetic landscape.
|
|
| 22. |
- Mugal, Carina F., et al.
(författare)
-
Conservation of Neutral Substitution Rate and Substitutional Asymmetries in Mammalian Genes
- 2010
-
Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 2:1, s. 19-28
-
Tidskriftsartikel (refereegranskat)abstract
- Local variation in neutral substitution rate across mammalian genomes is governed by several factors, including sequence context variables and structural variables. In addition, the interplay of replication and transcription, known to induce a strand bias in mutation rate, gives rise to variation in substitutional strand asymmetries. Here, we address the conservation of variation in mutation rate and substitutional strand asymmetries using primate-and rodent-specific repeat elements located within the introns of protein-coding genes. We find significant but weak conservation of local mutation rates between human and mouse orthologs. Likewise, substitutional strand asymmetries are conserved between human and mouse, where substitution rate asymmetries show a higher degree of conservation than mutation rate. Moreover, we provide evidence that replication and transcription are correlated to the strength of substitutional asymmetries. The effect of transcription is particularly visible for genes with highly conserved gene expression. In comparison with replication and transcription, mutation rate influences the strength of substitutional asymmetries only marginally.
|
|
| 23. |
- Mugal, Carina F., et al.
(författare)
-
Evolutionary Consequences of DNA Methylation on the GC Content in Vertebrate Genomes
- 2015
-
Ingår i: G3. - : Oxford University Press (OUP). - 2160-1836. ; 5:3, s. 441-447
-
Tidskriftsartikel (refereegranskat)abstract
- The genomes of many vertebrates show a characteristic variation in GC content. To explain its origin and evolution, mainly three mechanisms have been proposed: selection for GC content, mutation bias, and GC-biased gene conversion. At present, the mechanism of GC-biased gene conversion, i.e., short-scale, unidirectional exchanges between homologous chromosomes in the neighborhood of recombination-initiating double-strand breaks in favor for GC nucleotides, is the most widely accepted hypothesis. We here suggest that DNA methylation also plays an important role in the evolution of GC content in vertebrate genomes. To test this hypothesis, we investigated one mammalian (human) and one avian (chicken) genome. We used bisulfite sequencing to generate a whole-genome methylation map of chicken sperm and made use of a publicly available whole-genome methylation map of human sperm. Inclusion of these methylation maps into a model of GC content evolution provided significant support for the impact of DNA methylation on the local equilibrium GC content. Moreover, two different estimates of equilibrium GC content, one that neglects and one that incorporates the impact of DNA methylation and the concomitant CpG hypermutability, give estimates that differ by approximately 15% in both genomes, arguing for a strong impact of DNA methylation on the evolution of GC content. Thus, our results put forward that previous estimates of equilibrium GC content, which neglect the hypermutability of CpG dinucleotides, need to be reevaluated.
|
|
| 24. |
- Mugal, Carina F, et al.
(författare)
-
GC-biased gene conversion links the recombination landscape and demography to genomic base composition : GC-biased gene conversion drives genomic base composition across a wide range of species
- 2015
-
Ingår i: Bioessays. - : Wiley. - 0265-9247 .- 1521-1878. ; 37:12, s. 1317-1326
-
Tidskriftsartikel (refereegranskat)abstract
- The origin and evolutionary dynamics of the spatial heterogeneity in genomic base composition have been debated since its discovery in the 1970s. With the recent availability of numerous genome sequences from a wide range of species it has been possible to address this question from a comparative perspective, and similarities and differences in base composition between groups of organisms are becoming evident. Ample evidence suggests that the contrasting dynamics of base composition are driven by GC-biased gene conversion (gBGC), a process that is associated with meiotic recombination. In line with this hypothesis, base composition is associated with the rate of recombination and the evolutionary dynamics of the recombination landscape, therefore, governs base composition. In addition, and at first sight perhaps surprisingly, the relationship between demography and genomic base composition is in agreement with the gBGC hypothesis: organisms with larger populations have higher GC content than those with smaller populations.
|
|
| 25. |
- Mugal, Carina F., et al.
(författare)
-
Genome-wide analysis in chicken reveals that local levels of genetic diversity are mainly governed by the rate of recombination
- 2013
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 14, s. 86-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Polymorphism is key to the evolutionary potential of populations. Understanding which factors shape levels of genetic diversity within genomes forms a central question in evolutionary genomics and is of importance for the possibility to infer episodes of adaptive evolution from signs of reduced diversity. There is an on-going debate on the relative role of mutation and selection in governing diversity levels. This question is also related to the role of recombination because recombination is expected to indirectly affect polymorphism via the efficacy of selection. Moreover, recombination might itself be mutagenic and thereby assert a direct effect on diversity levels. Results: We used whole-genome re-sequencing data from domestic chicken (broiler and layer breeds) and its wild ancestor (the red jungle fowl) to study the relationship between genetic diversity and several genomic parameters. We found that recombination rate had the largest effect on local levels of nucleotide diversity. The fact that divergence (a proxy for mutation rate) and recombination rate were negatively correlated argues against a mutagenic role of recombination. Furthermore, divergence had limited influence on polymorphism. Conclusions: Overall, our results are consistent with a selection model, in which regions within a short distance from loci under selection show reduced polymorphism levels. This conclusion lends further support from the observations of strong correlations between intergenic levels of diversity and diversity at synonymous as well as non-synonymous sites. Our results also demonstrate differences between the two domestic breeds and red jungle fowl, where the domestic breeds show a stronger relationship between intergenic diversity levels and diversity at synonymous and non-synonymous sites. This finding, together with overall lower diversity levels in domesticates compared to red jungle fowl, seem attributable to artificial selection during domestication.
|
|
| 26. |
- Mugal, Carina Farah, 1981-
(författare)
-
Nucleotide Substitution Patterns in Vertebrate Genomes
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The rates and patterns at which nucleotide substitutions occur vary significantly across the genome sequence of vertebrates. A prominent example is the difference in the rate of evolution of functional sequences versus nonfunctional (neutrally evolving) sequences, which is explained by the influence of natural selection on functional sequences. However, even within neutrally evolving sequences there is striking variation in the rates and patterns of nucleotide substitutions. Unraveling the underlying processes that induce this variation is necessary to understand the basic principles of variation in neutral substitution profiles, which in turn is crucial for the identification of regions in the genome where natural selection acts. This research question builds the main focus of the present thesis. I have studied the causes and consequences of variation in different patterns of nucleotide substitutions. In particular, I have investigated substitutional strand asymmetries in mammalian genes and could show that they result from the asymmetric nature of DNA replication and transcription. Comparative analysis of substitutional asymmetries then suggested that the organization of DNA replication and the level of transcription are conserved among mammals. Further, I have examined the variation in CpG mutation rate among human genes and could show that beside DNA methylation also GC content plays a decisive role in CpG mutability. In addition, I have studied the signatures of GC-biased gene conversion and its impact on the evolution of the GC isochore structure in chicken. By comparison of the results in chicken to previous results in human I found evidence that karyotype stability is critical for the evolution of GC isochores. Finally, beside the empirical studies, I have performed theoretical investigations of substitution rates in functional sequences. More precisely, I have explored the temporal dynamics of estimates of the ratio of non-synonymous to synonymous substitution rates dN/dS in a phylogentic-population genetic framework.
|
|
| 27. |
- Mugal, Carina F., et al.
(författare)
-
Substitution rate variation at human CpG sites correlates with non-CpG divergence, methylation level and GC content
- 2011
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 12:6, s. R58-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A major goal in the study of molecular evolution is to unravel the mechanisms that induce variation in the germ line mutation rate and in the genome-wide mutation profile. The rate of germ line mutation is considerably higher for cytosines at CpG sites than for any other nucleotide in the human genome, an increase commonly attributed to cytosine methylation at CpG sites. The CpG mutation rate, however, is not uniform across the genome and, as methylation levels have recently been shown to vary throughout the genome, it has been hypothesized that methylation status may govern variation in the rate of CpG mutation.Results: Here, we use genome-wide methylation data from human sperm cells to investigate the impact of DNA methylation on the CpG substitution rate in introns of human genes. We find that there is a significant correlation between the extent of methylation and the substitution rate at CpG sites. Further, we show that the CpG substitution rate is positively correlated with non-CpG divergence, suggesting susceptibility to factors responsible for the general mutation rate in the genome, and negatively correlated with GC content. We only observe a minor contribution of gene expression level, while recombination rate appears to have no significant effect.Conclusions: Our study provides the first direct empirical support for the hypothesis that variation in the level of germ line methylation contributes to substitution rate variation at CpG sites. Moreover, we show that other genomic features also impact on CpG substitution rate variation.
|
|
| 28. |
|
|
| 29. |
- Mugal, Carina F., et al.
(författare)
-
Twisted Signatures of GC-Biased Gene Conversion Embedded in an Evolutionary Stable Karyotype
- 2013
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 30:7, s. 1700-1712
-
Tidskriftsartikel (refereegranskat)abstract
- The genomes of many vertebrates show a characteristic heterogeneous distribution of GC content, the so-called GC isochore structure. The origin of isochores has been explained via the mechanism of GC-biased gene conversion (gBGC). However, although the isochore structure is declining in many mammalian genomes, the heterogeneity in GC content is being reinforced in the avian genome. Despite this discrepancy, which remains unexplained, examinations of individual substitution frequencies in mammals and birds are both consistent with the gBGC model of isochore evolution. On the other hand, a negative correlation between substitution and recombination rate found in the chicken genome is inconsistent with the gBGC model. It should therefore be important to consider along with gBGC other consequences of recombination on the origin and fate of mutations, as well as to account for relationships between recombination rate and other genomic features. We therefore developed an analytical model to describe the substitution patterns found in the chicken genome, and further investigated the relationships between substitution patterns and several genomic features in a rigorous statistical framework. Our analysis indicates that GC content itself, either directly or indirectly via interrelations to other genomic features, has an impact on the substitution pattern. Further, we suggest that this phenomenon is particularly visible in avian genomes due to their unusually low rate of chromosomal evolution. Because of this, interrelations between GC content and other genomic features are being reinforced, and are as such more pronounced in avian genomes as compared with other vertebrate genomes with a less stable karyotype.
|
|
| 30. |
- Mugal, Carina F, et al.
(författare)
-
Why Time Matters : Codon Evolution and the Temporal Dynamics of dN/dS
- 2014
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 31:1, s. 212-231
-
Tidskriftsartikel (refereegranskat)abstract
- The ratio of divergence at nonsynonymous and synonymous sites, dN/dS, is a widely used measure in evolutionary genetic studies to investigate the extent to which selection modulates gene sequence evolution. Originally tailored to codon sequences of distantly related lineages, dN/dS represents the ratio of fixed nonsynonymous to synonymous differences. The impact of ancestral and lineage-specific polymorphisms on dN/dS, which we here show to be substantial for closely related lineages, is generally neglected in estimation techniques of dN/dS. To address this issue, we formulate a codon model that is firmly anchored in population genetic theory, derive analytical expressions for the dN/dS measure by Poisson random field approximation in a Markovian framework and validate the derivations by simulations. In good agreement, simulations and analytical derivations demonstrate that dN/dS is biased by polymorphisms at short time scales and that it can take substantial time for the expected value to settle at its time limit where only fixed differences are considered. We further show that in any attempt to estimate the dN/dS ratio from empirical data the effect of the intrinsic fluctuations of a ratio of stochastic variables, can even under neutrality yield extreme values of dN/dS at short time scales or in regions of low mutation rate. Taken together, our results have significant implications for the interpretation of dN/dS estimates, the McDonald-Kreitman test and other related statistics, in particular for closely related lineages.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Mugal, Carina, et al.
(författare)
-
Polymorphism Data Assist Estimation of the Nonsynonymous over Synonymous Fixation Rate Ratio omega for Closely Related Species
- 2020
-
Ingår i: Molecular biology and evolution. - : OXFORD UNIV PRESS. - 0737-4038 .- 1537-1719. ; 37:1, s. 260-279
-
Tidskriftsartikel (refereegranskat)abstract
- The ratio of nonsynonymous over synonymous sequence divergence, dN/dS, is a widely used estimate of the nonsynonymous over synonymous fixation rate ratio omega, which measures the extent to which natural selection modulates protein sequence evolution. Its computation is based on a phylogenetic approach and computes sequence divergence of protein-coding DNA between species, traditionally using a single representative DNA sequence per species. This approach ignores the presence of polymorphisms and relies on the indirect assumption that new mutations fix instantaneously, an assumption which is generally violated and reasonable only for distantly related species. The violation of the underlying assumption leads to a time-dependence of sequence divergence, and biased estimates of omega in particular for closely related species, where the contribution of ancestral and lineage-specific polymorphisms to sequence divergence is substantial. We here use a time-dependent Poisson random field model to derive an analytical expression of dN/dS as a function of divergence time and sample size. We then extend our framework to the estimation of the proportion of adaptive protein evolution alpha. This mathematical treatment enables us to show that the joint usage of polymorphism and divergence data can assist the inference of selection for closely related species. Moreover, our analytical results provide the basis for a protocol for the estimation of omega and alpha for closely related species. We illustrate the performance of this protocol by studying a population data set of four corvid species, which involves the estimation of omega and alpha at different time-scales and for several choices of sample sizes.
|
|
| 34. |
- Mugal, Carina, et al.
(författare)
-
Tissue-specific patterns of regulatory changes underlying gene expression differences among Ficedula flycatchers and their naturally occurring F1 hybrids
- 2020
-
Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 30:12, s. 1727-1739
-
Tidskriftsartikel (refereegranskat)abstract
- Changes in interacting cis- and trans-regulatory elements are important candidates for Dobzhansky-Muller hybrid incompatibilities and may contribute to hybrid dysfunction by giving rise to misexpression in hybrids. To gain insight into the molecular mechanisms and determinants of gene expression evolution in natural populations, we analyzed the transcriptome from multiple tissues of two recently diverged Ficedula flycatcher species and their naturally occurring F1 hybrids. Differential gene expression analysis revealed that the extent of differentiation between species and the set of differentially expressed genes varied across tissues. Common to all tissues, a higher proportion of Z-linked genes than autosomal genes showed differential expression, providing evidence for a fast-Z effect. We further found clear signatures of hybrid misexpression in brain, heart, kidney, and liver. However, while testis showed the highest divergence of gene expression among tissues, it showed no clear signature of misexpression in F1 hybrids, even though these hybrids were found to be sterile. It is therefore unlikely that incompatibilities between cis-trans regulatory changes explain the observed sterility. Instead, we found evidence that cis-regulatory changes play a significant role in the evolution of gene expression in testis, which illustrates the tissue-specific nature of cis-regulatory evolution bypassing constraints associated with pleiotropic effects of genes.
|
|
| 35. |
- Müller, Rebekka, et al.
(författare)
-
A Nearly Neutral Model of Molecular Signatures of Natural Selection after Change in Population Size
- 2022
-
Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 14:5
-
Tidskriftsartikel (refereegranskat)abstract
- The nearly neutral theory is a common framework to describe natural selection at the molecular level. This theory emphasizes the importance of slightly deleterious mutations by recognizing their ability to segregate and eventually get fixed due to genetic drift in spite of the presence of purifying selection. As genetic drift is stronger in smaller than in larger populations, a correlation between population size and molecular measures of natural selection is expected within the nearly neutral theory. However, this hypothesis was originally formulated under equilibrium conditions. As most natural populations are not in equilibrium, testing the relationship empirically may lead to confounded outcomes. Demographic nonequilibria, for instance following a change in population size, are common scenarios that are expected to push the selection-drift relationship off equilibrium. By explicitly modeling the effects of a change in population size on allele frequency trajectories in the Poisson random field framework, we obtain analytical solutions of the nonstationary allele frequency spectrum. This enables us to derive exact results of measures of natural selection and effective population size in a demographic nonequilibrium. The study of their time-dependent relationship reveals a substantial deviation from the equilibrium selection-drift balance after a change in population size. Moreover, we show that the deviation is sensitive to the combination of different measures. These results therefore constitute relevant tools for empirical studies to choose suitable measures for investigating the selection-drift relationship in natural populations. Additionally, our new modeling approach extends existing population genetics theory and can serve as foundation for methodological developments.
|
|
| 36. |
- Nam, Kiwoong, et al.
(författare)
-
Molecular evolution of genes in avian genomes
- 2010
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 11:6, s. R68-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Obtaining a draft genome sequence of the zebra finch (Taeniopygia guttata), the second bird genome to be sequenced, provides the necessary resource for whole-genome comparative analysis of gene sequence evolution in a non-mammalian vertebrate lineage. To analyze basic molecular evolutionary processes during avian evolution, and to contrast these with the situation in mammals, we aligned the protein-coding sequences of 8,384 1: 1 orthologs of chicken, zebra finch, a lizard and three mammalian species. Results: We found clear differences in the substitution rate at fourfold degenerate sites, being lowest in the ancestral bird lineage, intermediate in the chicken lineage and highest in the zebra finch lineage, possibly reflecting differences in generation time. We identified positively selected and/or rapidly evolving genes in avian lineages and found an over-representation of several functional classes, including anion transporter activity, calcium ion binding, cell adhesion and microtubule cytoskeleton. Conclusions: Focusing specifically on genes of neurological interest and genes differentially expressed in the unique vocal control nuclei of the songbird brain, we find a number of positively selected genes, including synaptic receptors. We found no evidence that selection for beneficial alleles is more efficient in regions of high recombination; in fact, there was a weak yet significant negative correlation between omega and recombination rate, which is in the direction predicted by the Hill-Robertson effect if slightly deleterious mutations contribute to protein evolution. These findings set the stage for studies of functional genetics of avian genes.
|
|
| 37. |
- Segami, Carolina, et al.
(författare)
-
Single-Cell Transcriptomics reveals relaxed evolutionary constraint of spermatogenesis in two passerine birds as compared to mammals
- 2022
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Spermatogenesis is a complex process where spermatogonia develop into haploid, mobile sperm cells. The genes guiding this process are subject to an evolutionary trade-off between preserving basic functions of sperm while acquiring new traits ensuring advantages in competition over fertilization of female gametes. In species with XY sex chromosomes, the outcome of this trade-off is found to vary across the stages of spermatogenesis but remains unexplored for species with ZW sex chromosomes. Here we characterize avian spermatogenesis at single cell resolution from testis of collared and pied flycatchers. We find evidence for relaxed evolutionary constraint of genes expressed in spermatocyte cells going through meiosis. An overrepresentation of Z-linked differentially expressed genes between the two species at this stage suggests that this relaxed constraint is associated with the lack of sex-chromosome silencing during meiosis. We conclude that the high throughput of bird spermatogenesis, at least partly, is explained by relaxed developmental constraint.
|
|
| 38. |
- Segami, Carolina, et al.
(författare)
-
The genomic basis of hybrid male sterility in Ficedula flycatchers
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Identifying genes involved in genetic incompatibilities causing hybrid sterility or inviability is a long-standing challenge in speciation research, especially in studies based on natural hybrid zones. Here we present the first high-probability candidate genes for hybrid male sterility in birds by using a combination of whole genome sequence data, histology sections of testis and single cell transcriptomics of testis samples from male pied-, collared-, and hybrid flycatchers. We reveal failure of meiosis in hybrid males and propose candidate genes involved in genetic incompatibilities causing this failure. Based on identification of genes with non-synonymous fixed differences between the two species and revealing missexpression patterns of these genes across the various stages of hybrid male spermatogenesis we conclude aberrant chromosome segregation and/or faulty chromatin packing. A lower proportion of spermatids produced by hybrid males implies that a proportion of the aberrant spermatids undergo apoptosis. Finally, we report an overrepresentation of Z-linkage of the revealed candidate incompatibility genes. Our results challenge the assumption that speciation processes are driven by fast evolving genes by showing that a few changes in genes with highly conserved and central functions may quickly ensure reproductive isolation through post-zygotic isolation.
|
|
| 39. |
- Smeds, Linnéa, et al.
(författare)
-
High-Resolution Mapping of Crossover and Non-crossover Recombination Events by Whole-Genome Re-sequencing of an Avian Pedigree
- 2016
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5
-
Tidskriftsartikel (refereegranskat)abstract
- Recombination is an engine of genetic diversity and therefore constitutes a key process in evolutionary biology and genetics. While the outcome of crossover recombination can readily be detected as shuffled alleles by following the inheritance of markers in pedigreed families, the more precise location of both crossover and non-crossover recombination events has been difficult to pinpoint. As a consequence, we lack a detailed portrait of the recombination landscape for most organisms and knowledge on how this landscape impacts on sequence evolution at a local scale. To localize recombination events with high resolution in an avian system, we performed whole-genome re-sequencing at high coverage of a complete three-generation collared flycatcher pedigree. We identified 325 crossovers at a median resolution of 1.4 kb, with 86% of the events localized to <10 kb intervals. Observed crossover rates were in excellent agreement with data from linkage mapping, were 52% higher in male (3.56 cM/Mb) than in female meiosis (2.28 cM/Mb), and increased towards chromosome ends in male but not female meiosis. Crossover events were non-randomly distributed in the genome with several distinct hot-spots and a concentration to genic regions, with the highest density in promoters and CpG islands. We further identified 267 non-crossovers, whose location was significantly associated with crossover locations. We detected a significant transmission bias (0.18) in favour of 'strong' (G, C) over 'weak' (A, T) alleles at non-crossover events, providing direct evidence for the process of GC-biased gene conversion in an avian system. The approach taken in this study should be applicable to any species and would thereby help to provide a more comprehensive portray of the recombination landscape across organism groups.
|
|
| 40. |
- Uebbing, Severin, et al.
(författare)
-
Divergence in gene expression within and between two closely related flycatcher species
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Compared to DNA sequence evolution, relatively little is known about the character of gene expression evolution as species diverge. For example, it is unclear if gene expression generally evolves in a clock-like manner (by stabilizing selection or from neutral evolution) or if there are frequent episodes of directional selection. To gain insights into the evolutionary divergence of gene expression patterns, we sequenced and compared the transcriptomes of multiple tissues from population samples of collared (Ficedula albicollis) and pied flycatchers (F. hypoleuca), a species pair which diverged less than one million years ago. Tissues resolved into separate clusters in non-metric multidimensional scaling ordination analysis and samples from the two species generally clustered by tissue rather than by species. Tissues differed in the degrees of expression variance within species and divergence between species. Variance was positively correlated with expression breadth and negatively correlated with protein interactivity, suggesting that pleiotropic constraints reduce gene expression variance within species. Variance was correlated with between-species divergence, consistent with a pattern expected from stabilizing selection and neutral evolution. Using an expression QST approach, we identified genes differentially expressed between species. We also identified 10 genes uniquely expressed in one of the species. For one such gene (DPP7, uniquely expressed in collared flycatcher), the absence of expression in pied flycatchers could be associated with a fixed ≈ 20 kb deletion including 11 out of 13 exons in this species. This study conducted in a young vertebrate speciation model system expands our knowledge of how gene expression evolves in natural populations.
|
|
| 41. |
- Uebbing, Severin, et al.
(författare)
-
Divergence in gene expression within and between two closely related flycatcher species
- 2016
-
Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 25:9, s. 2015-2028
-
Tidskriftsartikel (refereegranskat)abstract
- Relatively little is known about the character of gene expression evolution as species diverge. It is for instance unclear if gene expression generally evolves in a clock-like manner (by stabilizing selection or neutral evolution) or if there are frequent episodes of directional selection. To gain insights into the evolutionary divergence of gene expression, we sequenced and compared the transcriptomes of multiple organs from population samples of collared (Ficedula albicollis) and pied flycatchers (F. hypoleuca), two species which diverged less than one million years ago. Ordination analysis separated samples by organ rather than by species. Organs differed in their degrees of expression variance within species and expression divergence between species. Variance was negatively correlated with expression breadth and protein interactivity, suggesting that pleiotropic constraints reduce gene expression variance within species. Variance was correlated with between-species divergence, consistent with a pattern expected from stabilizing selection and neutral evolution. Using an expression PST approach, we identified genes differentially expressed between species and found 16 genes uniquely expressed in one of the species. For one of these, DPP7, uniquely expressed in collared flycatcher, the absence of expression in pied flycatcher could be associated with a ≈ 20 kb deletion including 11 out of 13 exons. This study of a young vertebrate speciation model system expands our knowledge of how gene expression evolves as natural populations become reproductively isolated.
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Ålund, Murielle, et al.
(författare)
-
Reproductive -omics of a wild avian speciation model unveils candidate genes for gamete interaction
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The complex nature of interspecific interactions contributing to reproductive isolation means that we still know little about their molecular basis. Male reproductive traits are notorious for their fast evolution at the phenotypic and genotypic level, and divergence in components of the ejaculate can lead to incompatibilities between closely related species. Making use of recent advances of molecular tools and the extensive knowledge on the biology and ecology of young sister species, here the pied (Ficedula hypoleuca) and collared flycatcher (F. albicollis), allows the identification of candidate phenotypes and the underlying genotypes maintaining species boundaries. Pied flycatcher females can avoid costly production of sterile hybrids when mated to collared flycatchers by cryptically favouring conspecific sperm. Here, we describe the testes transcriptome and sperm proteome of both species, confirm the complexity of avian sperm development and functions and identify several candidate genes for interactions between sperm and the female reproductive tract, using multiple independent measures of divergence between the species. We show that divergence at the transcriptional and translational levels can potentially lead to the evolution of reproductive incompatibilities despite low levels of sequence divergence, and suggest that integrating several -omics techniques with knowledge of the biology of naturally hybridizing species will greatly improve our understanding of the molecular basis of speciation in the near future.
|
|
