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Publications (10 of 38) Show all publications
Wheatcroft, D., Backström, N., Dutoit, L., McFarlane, S. E., Mugal, C. F., Wang, M., . . . Qvarnström, A. (2025). Divergence in expression of a singing-related neuroplasticity gene in the brains of 2 Ficedula flycatchers and their hybrids. G3: Genes, Genomes, Genetics, 15(2)
Open this publication in new window or tab >>Divergence in expression of a singing-related neuroplasticity gene in the brains of 2 Ficedula flycatchers and their hybrids
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2025 (English)In: G3: Genes, Genomes, Genetics, E-ISSN 2160-1836, Vol. 15, no 2Article in journal (Refereed) Published
Abstract [en]

Species-specific sexual traits facilitate species-assortative mating by reducing mating across species and reducing hybrid sexual attractiveness. For learned sexual traits, such as song in oscine birds, species distinctiveness can be eroded when species co-occur. Transcriptional regulatory divergence in brain regions involved in sensory learning is hypothesized to maintain species distinctiveness, but relatively few studies have compared gene expression in relevant brain regions between closely related species. Species differences in song are an important premating reproductive barrier between the collared (Ficedula albicollis) and pied flycatcher (F. hypoleuca). Here, we compare brain gene expression in adult males from each species and their naturally occurring F1 hybrids. We report overall conserved expression across species in a portion of the brain containing regions and nuclei known to be involved in song responses and learning. Further, among those genes that were differentially expressed between species, we find largely intermediate expression in hybrids. A single gene, SYT4 (synaptotagmin 4), known to be singing-associated, both was differentially expressed and has a putative upstream transcriptional regulatory factor containing fixed differences between the 2 species. Although a finer-scale investigation limited to song-specific regions may reveal further species differences, our findings provide insight into regulatory divergence in the brain between closely related species.

Place, publisher, year, edition, pages
Oxford University Press, 2025
Keywords
Ficedula, gene expression, song learning, speciation, STXBP4, SYT4
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-554858 (URN)10.1093/g3journal/jkae293 (DOI)001395823400001 ()39670717 (PubMedID)2-s2.0-85218222733 (Scopus ID)
Funder
Swedish Research Council, 2013-8271Swedish Research Council, 2012-3722Knut and Alice Wallenberg Foundation, 2014/0044
Available from: 2025-04-17 Created: 2025-04-17 Last updated: 2025-04-17Bibliographically approved
Kaj, I., Mugal, C. F. & Müller-Widmann, R. (2024). A Wright-Fisher graph model and the impact of directional selection on genetic variation. Theoretical Population Biology, 159, 13-24
Open this publication in new window or tab >>A Wright-Fisher graph model and the impact of directional selection on genetic variation
2024 (English)In: Theoretical Population Biology, ISSN 0040-5809, E-ISSN 1096-0325, Vol. 159, p. 13-24Article in journal (Refereed) Published
Abstract [en]

We introduce a multi-allele Wright-Fisher model with mutation and selection such that allele frequencies at a single locus are traced by the path of a hybrid jump-diffusion process. The state space of the process is given by the vertices and edges of a topological graph, i.e. edges are unit intervals. Vertices represent monomorphic population states and positions on the edges mark the biallelic proportions of ancestral and derived alleles during polymorphic segments. In this setting, mutations can only occur at monomorphic loci. We derive the stationary distribution in mutation-selection-drift equilibrium and obtain the expected allele frequency spectrum under large population size scaling. For the extended model with multiple independent loci we derive rigorous upper bounds for a wide class of associated measures of genetic variation. Within this framework we present mathematically precise arguments to conclude that the presence of directional selection reduces the magnitude of genetic variation, as constrained by the bounds for neutral evolution.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Wright-Fisher jump-diffusion process, Directional selection, Mutation bias, Genetic diversity, Effective mutation rate, Theoretical population genetics
National Category
Evolutionary Biology Genetics and Genomics
Identifiers
urn:nbn:se:uu:diva-536967 (URN)10.1016/j.tpb.2024.07.004 (DOI)001284518200001 ()39019334 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2014/0044Swedish Research Council, 2013-8271
Available from: 2024-08-30 Created: 2024-08-30 Last updated: 2025-03-18Bibliographically approved
Boman, J., Qvarnström, A. & Mugal, C. (2024). Regulatory and evolutionary impact of DNA methylation in two songbird species and their naturally occurring F1 hybrids. BMC Biology, 22(1), Article ID 124.
Open this publication in new window or tab >>Regulatory and evolutionary impact of DNA methylation in two songbird species and their naturally occurring F1 hybrids
2024 (English)In: BMC Biology, E-ISSN 1741-7007, Vol. 22, no 1, article id 124Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024
Keywords
DNA methylation, Speciation, Transcriptomics, Epigenomics
National Category
Genetics and Genomics Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-531095 (URN)10.1186/s12915-024-01920-2 (DOI)001234529800003 ()38807214 (PubMedID)
Funder
Swedish Research Council, 2013- 8271Swedish Research Council, 2012-3722Swedish Research Council, 2022-06725Knut and Alice Wallenberg Foundation, 2014/0044
Available from: 2024-06-12 Created: 2024-06-12 Last updated: 2025-02-01Bibliographically approved
Chase, M., Vilcot, M. & Mugal, C. (2024). The role of recombination dynamics in shaping signatures of direct and indirect selection across the Ficedula flycatcher genome. Proceedings of the Royal Society of London. Biological Sciences, 291(2015), Article ID 20232382.
Open this publication in new window or tab >>The role of recombination dynamics in shaping signatures of direct and indirect selection across the Ficedula flycatcher genome
2024 (English)In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 291, no 2015, article id 20232382Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Royal SocietyROYAL SOC, 2024
Keywords
meiotic recombination, linked selection, direct selection, speciation, Hill-Robertson interference
National Category
Evolutionary Biology Genetics and Genomics
Identifiers
urn:nbn:se:uu:diva-522914 (URN)10.1098/rspb.2023.2382 (DOI)001143698500008 ()38228173 (PubMedID)
Funder
Swedish Research Council, 2013-8271Knut and Alice Wallenberg Foundation, 2014/0044Swedish National Infrastructure for Computing (SNIC)Swedish Research Council, 2022-06725Swedish Research Council, 2018-05973
Available from: 2024-02-13 Created: 2024-02-13 Last updated: 2025-02-01Bibliographically approved
Müller, R., Kaj, I. & Mugal, C. (2022). A Nearly Neutral Model of Molecular Signatures of Natural Selection after Change in Population Size. Genome Biology and Evolution, 14(5), Article ID evac058.
Open this publication in new window or tab >>A Nearly Neutral Model of Molecular Signatures of Natural Selection after Change in Population Size
2022 (English)In: Genome Biology and Evolution, E-ISSN 1759-6653, Vol. 14, no 5, article id evac058Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Oxford University PressOxford University Press (OUP), 2022
Keywords
nonequilibrium theory, nearly neutral theory, demographic nonequilibrium, theoretical population genetics, selection-drift balance
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-476167 (URN)10.1093/gbe/evac058 (DOI)000799968600001 ()35478252 (PubMedID)
Funder
Swedish Research Council, 2013/08271Knut and Alice Wallenberg Foundation
Available from: 2022-06-09 Created: 2022-06-09 Last updated: 2025-03-18Bibliographically approved
Segami, C., Semon, M., Cunha, C., Bergin, C., Mugal, C. & Qvarnström, A. (2022). Single-Cell Transcriptomics reveals relaxed evolutionary constraint of spermatogenesis in two passerine birds as compared to mammals.
Open this publication in new window or tab >>Single-Cell Transcriptomics reveals relaxed evolutionary constraint of spermatogenesis in two passerine birds as compared to mammals
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2022 (English)Manuscript (preprint) (Other academic)
Abstract [en]

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.

National Category
Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-470337 (URN)10.1101/2022.01.22.477241 (DOI)
Funder
Swedish Research Council, 2016–05138Knut and Alice Wallenberg FoundationSwedish Research Council, 2012–03722Swedish Research Council, 2013/08271Swedish National Infrastructure for Computing (SNIC)Wenner-Gren Foundations
Available from: 2022-03-23 Created: 2022-03-23 Last updated: 2022-10-26Bibliographically approved
Chase, M. A., Ellegren, H. & Mugal, C. F. (2021). Positive selection plays a major role in shaping signatures of differentiation across the genomic landscape of two independent Ficedula flycatcher species pairs. Evolution, 75(9), 2179-2196
Open this publication in new window or tab >>Positive selection plays a major role in shaping signatures of differentiation across the genomic landscape of two independent Ficedula flycatcher species pairs
2021 (English)In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 75, no 9, p. 2179-2196Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & SonsWiley, 2021
Keywords
Linked selection, recombination rate, selective sweep, speciation genomics
National Category
Evolutionary Biology Genetics and Genomics
Identifiers
urn:nbn:se:uu:diva-468157 (URN)10.1111/evo.14234 (DOI)000646158400001 ()33851440 (PubMedID)
Funder
Swedish Research Council, 2013-8271Knut and Alice Wallenberg Foundation, 2014/0044Swedish National Infrastructure for Computing (SNIC)
Available from: 2022-02-22 Created: 2022-02-22 Last updated: 2025-02-01Bibliographically approved
Boman, J., Mugal, C. F. & Backström, N. (2021). The Effects of GC-Biased Gene Conversion on Patterns of Genetic Diversity among and across Butterfly Genomes. Genome Biology and Evolution, 13(5), Article ID evab064.
Open this publication in new window or tab >>The Effects of GC-Biased Gene Conversion on Patterns of Genetic Diversity among and across Butterfly Genomes
2021 (English)In: Genome Biology and Evolution, E-ISSN 1759-6653, Vol. 13, no 5, article id evab064Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Oxford University Press, 2021
Keywords
genetic diversity, GC-biased gene conversion, Lepidoptera, linked selection, mutation bias
National Category
Genetics and Genomics Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-448813 (URN)10.1093/gbe/evab064 (DOI)000661527400011 ()33760095 (PubMedID)
Funder
Swedish Research Council, VR 20134508Swedish Research Council, VR 2019-04791Swedish Research Council, 2018-05973Swedish National Infrastructure for Computing (SNIC)
Available from: 2021-07-09 Created: 2021-07-09 Last updated: 2025-02-01Bibliographically approved
Mugal, C., Kutschera, V. E., Botero-Castro, F., Wolf, J. B. W. & Kaj, I. (2020). Polymorphism Data Assist Estimation of the Nonsynonymous over Synonymous Fixation Rate Ratio omega for Closely Related Species. Molecular biology and evolution, 37(1), 260-279
Open this publication in new window or tab >>Polymorphism Data Assist Estimation of the Nonsynonymous over Synonymous Fixation Rate Ratio omega for Closely Related Species
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2020 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 37, no 1, p. 260-279Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2020
Keywords
molecular evolution, codon models, dN/dS, natural selection, population genetics, Poisson random field model
National Category
Genetics and Genomics Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-407504 (URN)10.1093/molbev/msz203 (DOI)000515121200021 ()31504782 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council, 2013/08271EU, European Research Council, ERCStG-336536
Available from: 2020-03-26 Created: 2020-03-26 Last updated: 2025-02-01Bibliographically approved
Mugal, C., Wang, M., Backström, N., Wheatcroft, D., Ålund, M., Sémon, M., . . . Ellegren, H. (2020). Tissue-specific patterns of regulatory changes underlying gene expression differences among Ficedula flycatchers and their naturally occurring F1 hybrids. Genome Research, 30(12), 1727-1739
Open this publication in new window or tab >>Tissue-specific patterns of regulatory changes underlying gene expression differences among Ficedula flycatchers and their naturally occurring F1 hybrids
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2020 (English)In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 30, no 12, p. 1727-1739Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Genetics and Genomics Evolutionary Biology
Identifiers
urn:nbn:se:uu:diva-432957 (URN)10.1101/gr.254508.119 (DOI)000596075800004 ()33144405 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2014/0044Swedish Research Council, 2013-8271Swedish Research Council, 2012-3722Swedish National Infrastructure for Computing (SNIC)
Available from: 2021-01-26 Created: 2021-01-26 Last updated: 2025-02-01Bibliographically approved
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