uu.seUppsala University Publications
Change search
Refine search result
1 - 24 of 24
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Bolivar, Paulina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Gueguen, Laurent
    Univ Claude Bernard Lyon 1, CNRS, UMR 5558, Lab Biol & Biometrie Evolut, Lyon, France.
    Duret, Laurent
    Univ Claude Bernard Lyon 1, CNRS, UMR 5558, Lab Biol & Biometrie Evolut, Lyon, France.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    GC-biased gene conversion conceals the prediction of the nearly neutral theory in avian genomes2019In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 20, article id 5Article in journal (Refereed)
    Abstract [en]

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

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

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

  • 2.
    Bolivar, Paulina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Sebastiano, Matteo Rossi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Ludwig Maximilians Univ Munchen, Fac Biol, Dept Biol 2, Planegg Martinsried, Germany.
    Nater, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Univ Konstanz, Dept Biol, Chair Zool & Evolutionary Biol, Constance, Germany.
    Wang, Mi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Dutoit, Ludovic
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Biased Inference of Selection Due to GC-Biased Gene Conversion and the Rate of Protein Evolution in Flycatchers When Accounting for It2018In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 35, no 10, p. 2475-2486Article in journal (Refereed)
    Abstract [en]

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

  • 3.
    Bolívar, Paulina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina F
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nater, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Recombination Rate Variation Modulates Gene Sequence Evolution Mainly via GC-Biased Gene Conversion, Not Hill-Robertson Interference, in an Avian System2016In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 33, no 1, p. 216-227Article in journal (Refereed)
    Abstract [en]

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

  • 4.
    Burri, Reto
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nater, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Kawakami, Takeshi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina F.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ólason, Páll I.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Smeds, Linnea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Suh, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Dutoit, Ludovic
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Bures, Stanislav
    Palacky Univ, Dept Zool, Lab Ornithol, Olomouc 77146, Czech Republic..
    Garamszegi, Laszlo Z.
    CSIC, Dept Evolutionary Ecol, Estn Biol Donana, Seville 41092, Spain..
    Hogner, Silje
    Univ Oslo, Ctr Ecol & Evolutionary Synth, Dept Biosci, N-0316 Oslo, Norway.;Univ Oslo, Nat Hist Museum, N-0318 Oslo, Norway..
    Moreno, Juan
    CSIC, Museo Nacl Ciencias Nat, E-28006 Madrid, Spain..
    Qvarnström, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Ruzic, Milan
    Bird Protect & Study Soc Serbia, Novi Sad 21000, Serbia..
    Saether, Stein-Are
    Univ Oslo, Ctr Ecol & Evolutionary Synth, Dept Biosci, N-0316 Oslo, Norway.;Norwegian Inst Nat Res NINA, N-7034 Trondheim, Norway..
    Saetre, Glenn-Peter
    Univ Oslo, Ctr Ecol & Evolutionary Synth, Dept Biosci, N-0316 Oslo, Norway..
    Toeroek, Janos
    Eotvos Lorand Univ, Dept Systemat Zool & Ecol, Behav Ecol Grp, H-1117 Budapest, Hungary..
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Linked selection and recombination rate variation drive the evolution of the genomic landscape of differentiation across the speciation continuum of Ficedula flycatchers2015In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 25, no 11, p. 1656-1665Article in journal (Refereed)
    Abstract [en]

    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.

  • 5.
    Dutoit, Ludovic
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Burri, Reto
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nater, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina F.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Hans, Ellegren
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Genomic distribution and estimation of nucleotide diversity in natural populations: perspectives from the collared flycatcher (Ficedula albicollis) genome2017In: Molecular Ecology Resources, ISSN 1755-098X, E-ISSN 1755-0998, Vol. 17, no 4, p. 586-597Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Dutoit, Ludovic
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Bolivar, Paulina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Wang, Mi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nadachowska-Brzyska, Krystyna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Smeds, Linnea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Gustafsson, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Sex-biased gene expression, sexual antagonism and levels of genetic diversity in the collared flycatcher (Ficedula albicollis) genome2018In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 27, no 18, p. 3572-3581Article in journal (Other academic)
    Abstract [en]

    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.

  • 7.
    Dutoit, Ludovic
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Vijay, Nagarjun
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Univ Michigan, Dept Ecol & Evolutionary Biol, Lab Mol & Genom Evolut, Ann Arbor, MI USA..
    Mugal, Carina F.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Bossu, Christen M.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Stockholm Univ, Dept Zool, S-10691 Stockholm, Sweden.
    Burri, Reto
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Friedrich Schiller Univ, Inst Ecol, Dept Ecol, Dornburger Str 159 07743 Jena, Jena, Germany.
    Wolf, Jochen
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Ludwig Maximilians Univ Munchen, Fac Biol 2, Div Evolutionary Biol, Grosshaderner Str 2, D-82152 Martinsried, Germany..
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Covariation in levels of nucleotide diversity in homologous regions of the avian genome long after completion of lineage sorting2017In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 284, no 1849, article id 20162756Article in journal (Refereed)
    Abstract [en]

    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.

  • 8. Hart, M. W.
    et al.
    Stover, D.
    Mozaffari, S. , V
    Ober, C.
    Mugal, Carina Farah
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Kaj, Ingemar
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Selection on coevolving human gamete recognition genes2016In: Integrative and Comparative Biology, ISSN 1540-7063, E-ISSN 1557-7023, Vol. 56, p. E84-E84Article in journal (Other academic)
  • 9.
    Hart, Michael W.
    et al.
    Simon Fraser University, Department of Biological Science, Burnaby.
    Stover, Daryn A.
    Arizona State University Colleges at Lake Havasu City, School of Mathematical and Natural Sciences.
    Guerra, Vanessa
    Simon Fraser University, Department of Biological Science, Burnaby.
    Mozaffari, Sahar V.
    University of Chicago, Department of Human Genetics.
    Ober, Carole
    University of Chicago, Department of Human Genetics.
    Mugal, Carina F.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Kaj, Ingemar
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Positive selection on human gamete-recognition genes2018In: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 6, article id e4259Article in journal (Refereed)
    Abstract [en]

    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.

  • 10.
    Kaj, Ingemar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Mugal, Carina F.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    The non-equilibrium allele frequency spectrum in a Poisson random field framework2016In: Theoretical Population Biology, ISSN 0040-5809, E-ISSN 1096-0325, Vol. 111, p. 51-64Article in journal (Refereed)
    Abstract [en]

    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.

  • 11.
    Kawakami, Takeshi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Univ Sheffield, Dept Anim & Plant Sci, Sheffield, S Yorkshire, England..
    Mugal, Carina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Suh, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nater, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Univ Zurich, Dept Evolutionary Biol & Environm Studies, Zurich, Switzerland..
    Burri, Reto
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Friedrich Schiller Univ Jena, Dept Populat Ecol, Jena, Germany..
    Smeds, Linnea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Whole-genome patterns of linkage disequilibrium across flycatcher populations clarify the causes and consequences of fine-scale recombination rate variation in birds2017In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 26, no 16, p. 4158-4172Article in journal (Refereed)
    Abstract [en]

    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.

  • 12.
    Kawakami, Takeshi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Smeds, Linnea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Backstrom, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Husby, Arild
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Qvarnström, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Mugal, Carina F.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ólason, Páll
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    A high-density linkage map enables a second-generation collared flycatcher genome assembly and reveals the patterns of avian recombination rate variation and chromosomal evolution2014In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 23, no 16, p. 4035-4058Article, review/survey (Refereed)
    Abstract [en]

    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.

  • 13.
    Mugal, Carina F.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Arndt, Peter F.
    Max Planck Institute for Molecular Genetics, Berlin, Department of Computational Molecular Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Twisted Signatures of GC-Biased Gene Conversion Embedded in an Evolutionary Stable Karyotype2013In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 30, no 7, p. 1700-1712Article in journal (Refereed)
    Abstract [en]

    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.

  • 14.
    Mugal, Carina F.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Arndt, Peter F.
    Holm, Lena
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Evolutionary Consequences of DNA Methylation on the GC Content in Vertebrate Genomes2015In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 5, no 3, p. 441-447Article in journal (Refereed)
    Abstract [en]

    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.

  • 15.
    Mugal, Carina F.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Substitution rate variation at human CpG sites correlates with non-CpG divergence, methylation level and GC content2011In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 12, no 6, p. R58-Article in journal (Refereed)
    Abstract [en]

    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.

  • 16.
    Mugal, Carina F.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nabholz, Benoit
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Genome-wide analysis in chicken reveals that local levels of genetic diversity are mainly governed by the rate of recombination2013In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 14, p. 86-Article in journal (Refereed)
    Abstract [en]

    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.

  • 17.
    Mugal, Carina F.
    et al.
    Karl-Franzens University Graz, Graz, Austria.
    von Grünberg, Hans-Hennig
    Peifer, Martin
    Transcription-induced mutational strand bias and its effect on substitution rates in human genes2009In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 26, no 1, p. 131-142Article in journal (Refereed)
  • 18.
    Mugal, Carina F
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Weber, Claudia C
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    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 species2015In: Bioessays, ISSN 0265-9247, E-ISSN 1521-1878, Vol. 37, no 12, p. 1317-1326Article in journal (Refereed)
    Abstract [en]

    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.

  • 19.
    Mugal, Carina F
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Wolf, Jochen B W
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Kaj, Ingemar
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics.
    Why Time Matters: Codon Evolution and the Temporal Dynamics of dN/dS2014In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 31, no 1, p. 212-231Article in journal (Refereed)
    Abstract [en]

    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.

  • 20.
    Mugal, Carina F.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Wolf, Jochen
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    von Gruenberg, H. H.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Conservation of Neutral Substitution Rate and Substitutional Asymmetries in Mammalian Genes2010In: Genome Biology and Evolution, ISSN 1759-6653, Vol. 2, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    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.

  • 21.
    Mugal, Carina Farah
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nucleotide Substitution Patterns in Vertebrate Genomes2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    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.

     

    List of papers
    1. Conservation of Neutral Substitution Rate and Substitutional Asymmetries in Mammalian Genes
    Open this publication in new window or tab >>Conservation of Neutral Substitution Rate and Substitutional Asymmetries in Mammalian Genes
    2010 (English)In: Genome Biology and Evolution, ISSN 1759-6653, Vol. 2, no 1, p. 19-28Article in journal (Refereed) Published
    Abstract [en]

    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.

    Keywords
    neutral substitution rate, substitutional strand asymmetries, transcription-induced mutation, gene expression conservation
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-135745 (URN)10.1093/gbe/evp056 (DOI)000280480000003 ()
    Available from: 2010-12-08 Created: 2010-12-08 Last updated: 2018-02-22Bibliographically approved
    2. Substitution rate variation at human CpG sites correlates with non-CpG divergence, methylation level and GC content
    Open this publication in new window or tab >>Substitution rate variation at human CpG sites correlates with non-CpG divergence, methylation level and GC content
    2011 (English)In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 12, no 6, p. R58-Article in journal (Refereed) Published
    Abstract [en]

    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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-162402 (URN)10.1186/gb-2011-12-6-r58 (DOI)000296646600006 ()
    Available from: 2011-11-30 Created: 2011-11-30 Last updated: 2018-02-22Bibliographically approved
    3. Twisted Signatures of GC-Biased Gene Conversion Embedded in an Evolutionary Stable Karyotype
    Open this publication in new window or tab >>Twisted Signatures of GC-Biased Gene Conversion Embedded in an Evolutionary Stable Karyotype
    2013 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 30, no 7, p. 1700-1712Article in journal (Refereed) Published
    Abstract [en]

    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.

    National Category
    Evolutionary Biology Genetics
    Research subject
    Biology with specialization in Molecular Evolution
    Identifiers
    urn:nbn:se:uu:diva-198785 (URN)10.1093/molbev/mst067 (DOI)000321056200019 ()
    Available from: 2013-04-25 Created: 2013-04-25 Last updated: 2018-02-22Bibliographically approved
    4. Why time matters: Codon evolution and the temporal dynamics of dN/dS
    Open this publication in new window or tab >>Why time matters: Codon evolution and the temporal dynamics of dN/dS
    (English)Manuscript (preprint) (Other academic)
    National Category
    Evolutionary Biology Genetics
    Research subject
    Biology with specialization in Molecular Evolution
    Identifiers
    urn:nbn:se:uu:diva-198786 (URN)
    Available from: 2013-04-25 Created: 2013-04-25 Last updated: 2013-08-30
  • 22.
    Nam, Kiwoong
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nabholz, Benoit
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Schielzeth, Holger
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Wolf, Jochen B. W.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Backström, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Künstner, Axel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Balakrishnan, Christopher N.
    Heger, Andreas
    Ponting, Chris P.
    Clayton, David F.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Molecular evolution of genes in avian genomes2010In: Genome Biology, ISSN 1474-760X, Vol. 11, no 6, p. R68-Article in journal (Refereed)
    Abstract [en]

    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.

  • 23.
    Smeds, Linnéa
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina F
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Qvarnström, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    High-Resolution Mapping of Crossover and Non-crossover Recombination Events by Whole-Genome Re-sequencing of an Avian Pedigree2016In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, no 5, article id e1006044Article in journal (Refereed)
    Abstract [en]

    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.

  • 24.
    Uebbing, Severin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Künstner, Axel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Mäkinen, Hannu
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Backström, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Bolivar, Paulina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Burri, Reto
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Dutoit, Ludovic
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mugal, Carina F.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nater, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Aken, Bronwen
    Flicek, Paul
    Martin, Fergal J
    Searle, Stephen M J
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Divergence in gene expression within and between two closely related flycatcher species2016In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 25, no 9, p. 2015-2028Article in journal (Refereed)
    Abstract [en]

    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.

1 - 24 of 24
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf