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- Axelsson, Erik, 1975-
(författare)
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Comparative Genomics in Birds
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To shed light on forces that shape the molecular evolution of bird genomes, and in turn avian adaptations, comparative analyses of avian DNA sequences are important. Moreover, contrasting findings in birds to those of other organisms will lend a clearer view on general aspects of molecular evolution. However, few such analyses have been conducted in birds. Progress is presented in this thesis.Theories predict a reduction in the mutation rate of the Z chromosome as the harmful effects of recessive mutations are exposed in female birds. We find no evidence for this. Instead, the substitution rates of sex chromosomes and autosomes are largely compatible with expectations from male-biased mutation. This suggests that a majority of mutations arise during DNA replication.Substitution rates also vary across chicken autosomes. For instance, microchromosomes accumulate ~20% more substitutions than macrochromosomes. We show that a majority of the autosomal variation in substitution rate can be accounted for by GC content, mainly due to the incidence of mutable CpG-dinucleotides.Sequence comparisons also show that the pattern of nucleotide substitution varies in the chicken genome and this reinforces regional differences in base composition. The level of selective constraint in at least some avian lineages is higher than in mammalian lineages as indicated by low dN/dS – ratios. Larger historical population sizes of birds relative to mammals could explain this observation. Within the avian genome, the dN/dS is lower for genes on micro- than macrochromosomes, potentially owing to a higher incidence of house-keeping genes in the former category.Contrasting data on non-synonymous and synonymous substitution for divergence and polymorphism shows that positive selection has contributed more to the evolution of Z-linked than autosomal genes. This is likely explained by the full exposure of beneficial recessive mutations on Z when in female birds.
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| 4. |
- Backström, Niclas, 1969-
(författare)
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Gene Mapping in Ficedula Flycatchers
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In order to get full understanding of how evolution proceeds in natural settings it is necessary to reveal the genetic basis of the phenotypic traits that play a role for individual fitness in different environments. There are a few possible approaches, most of which stem from traditional mapping efforts in domestic animals and other model species. Here we set the stage for gene mapping in natural populations of birds by producing a large number of anchor markers of broad utility for avian genetical research and use these markers to generate a genetic map of the collared flycatcher (Ficedula albicollis). The map reveals a very high degree of synteny and gene order conservation between bird species separated by as much as 100 million years. This is encouraging for later stages of mapping procedures in natural populations since this means that there is a possibility to use the information from already characterized avian genomes to track candidate genes for detailed analysis in non-model species. One interesting aspect of the low degree of rearrangements occurring in the avian genomes is that this could play a role in the low rate of hybridization barriers formed in birds compared to for instance mammals. An analysis of Z-linked gene markers reveals relatively long-range linkage disequilibrium (LD) in collared flycatchers compared to other outbred species but still, LD seems to decay within < 50 kb indicating that > 20.000 markers would be needed to cover the genome in an association scan. A detailed scan of 74 Z-linked genes evenly distributed along the chromosome in both the collared flycatcher and the pied flycatcher (Ficedula hypoleuca) indicates that there are regions that evolve under directional selection, regions that might harbor loci of importance for adaptive divergence and/or hybrid inviability.
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| 5. |
- Berggren Bremdal, Karin, 1978-
(författare)
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Evolution of MHC Genes and MHC Gene Expression
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Polymorphism in coding regions and regions controlling gene expression is the major determinant of adaptive differences in natural populations. Genes of the major histocompatibility complex (MHC) possess a high level of genetic variation, which is maintained by selection over long coalescence times. MHC genes encode antigen-presenting molecules in the adaptive immune system, which protects the host from infectious diseases. However, MHC molecules may also present self-peptides and for most autoimmune diseases there is a genetic factor associated with the MHC. MHC genes have been used to learn about the interplay of selection and historical population events. In domestic dogs and their progenitor, the wolf, I explored factors associated with domestication and breed formation and their influence not only on MHC coding regions but also on the haplotypic structure of the class II region. Polymorphism and strong selection was demonstrated in the proximal promoters of MHC genes in dogs and wolves. Hence, genetic variation associated with MHC gene expression may have at least equal importance for a well functioning immune system. Associations between promoter sequences and particular coding alleles suggested allele-specific expression patterns. SNP haplotypes of the MHC class II region revealed ancestral as well as convergent haplotypes, in which combinations of alleles are kept by selection. Interestingly, weaker allelic associations were found between different genes and between coding regions and promoters in dogs compared to wolves. Potentially, this could cause insufficient defense against infections and predispose dogs to autoimmune diseases. For example, I identified a site in the promoter region that showed a consistent difference between haplotypes conferring susceptibility and protection to diabetes in dogs, which should be investigated further. Furthermore, I investigated how selection and demographic changes associated with glacial and inter-glacial periods have affected MHC variation in European hedgehogs and extended the prevailing knowledge concerning their population history.
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| 6. |
- Berlin, Sofia, 1973-
(författare)
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The Effects of Mutation and Selection on the Rate and Pattern of Molecular Evolution in Birds
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- By comparing sequence diversity and divergence on sex chromosomes one can study how the rate of evolution in affected by mutation and/or selection. The rate of mutation in male biased, meaning that relatively more mutations are created in the male germ line than in the female. Since the male mutation bias (αm) most likely is a consequence of the difference in cell divisions between male and female germ lines, life history characters that affect this difference should covary with αm. Indeed, we found a positive correlation between estimates of αm and increased generation times and increased intensity of sperm competition. We have also found that estimates of αm varied significantly between gametologous introns located on the sex chromosomes. This could be a consequence of the variation in substitution rates between loci. Population genetics theory predicts that both positive and negative selection reduce genetic diversity around a selected locus at a distance determined by the rate of recombination. Consequently, a non-recombining chromosome, like the female specific W chromosome in birds, selection is expected to have a large impact on sequence diversity. Indeed, in a large sequence screening we found only one segregating site among 7643 base pairs sequenced in 47 chicken females. Furthermore, we also found that deleterious substitutions are fixed in a higher rate for W- than Z-linked sequences, which is in agreement with the lack of recombination and strong genetic drift due to the low effective population size. Rarely non-synonymous mutations are beneficial for an individual, but when it happens, the mutation is positively selected and rapidly reaches fixation in a population. We have found that positive selection has been acting on the female reproductive protein, zona pellucida c in birds. This rapid evolution is likely a mechanism to prevent hybridisation.
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| 7. |
- Bolívar, Paulina
(författare)
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Rates and patterns of molecular evolution in avian genomes
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Evolution is the change in inherited characteristics of a population through subsequent generations. The interplay of several evolutionary mechanisms determines the rate at which this change occurs. In short, genetic variation is generated though mutation, and the fate of these mutations in a population is determined mainly by the combined effect of genetic drift, natural selection and recombination. Elucidating the relative impact of these mechanisms is complex; making it a long-standing question in evolutionary biology. In this thesis, I focus on disentangling the relative roles of these evolutionary mechanisms and genetic factors in determining rates and patterns of evolution at the molecular level, by studying variation in the DNA sequence of multiple avian species, and in particular the collared flycatcher (Ficedula albicollis). Specifically, I aim to further our understanding regarding the impact of recombination rate on genome evolution, through its interaction with the efficacy of selection and through the process of GC-biased gene conversion (gBGC), which has been poorly characterized in birds. I demonstrate that gBGC has a pervasive effect on the genome of the collared flycatcher and other avian species, as it increases the substitution rate and affects interpretations of the impact of natural selection and adaptation. Interestingly, its effect is even stronger in neutrally evolving sites compared to sites evolving under selection. After accounting for gBGC, I disentangle the true impact of natural selection versus non-adaptive processes in determining rates of molecular evolution in the collared flycatcher genome, shedding light on the process of adaptation. Finally, I demonstrate the significant role of recombination through its impact on linked selection, along with mutation rate differences, in determining relative levels of genetic diversity and their relationship to the fast-Z effect across the avian phylogeny. This thesis urges future studies to account for the effect of recombination before interpreting patterns of selection in sequence evolution.
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| 10. |
- Brandström, Mikael, 1978-
(författare)
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Bioinformatic Analysis of Mutation and Selection in the Vertebrate Non-coding Genome
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The majority of the vertebrate genome sequence is not coding for proteins. In recent years, the evolution of this noncoding fraction of the genome has gained interest. These studies have been greatly facilitated by the availability of full genome sequences. The aim of this thesis is to study evolution of the noncoding vertebrate genome through bioinformatic analysis of large-scale genomic datasets.In a first analysis we addressed the use of conservation of sequence between highly diverged genomes to infer function. We provided evidence for a turnover of the patterns of negative selection. Hence, measures of constraint based on comparisons of diverged genomes might underestimate the functional proportion of the genome.In the following analyses we focused on length variation as found in small-scale insertion and deletion (indel) polymorphisms and microsatellites. For indels in chicken, replication slippage is a likely mutation mechanism, as a large proportion of the indels are parts of tandem-duplicates. Using a set of microsatellite polymorphisms in chicken, where we avoid ascertainment bias, we showed that polymorphism is positively correlated with microsatellite length and AT-content. Furthermore, interruptions in the microsatellite sequence decrease the levels of polymorphism.We also analysed the association between microsatellite polymorphism and recombination in the human genome. Here we found increased levels of microsatellite polymorphism in human recombination hotspots and also similar increases in the frequencies of single nucleotide polymorphisms (SNPs) and indels. This points towards natural selection shaping the levels of variation. Alternatively, recombination is mutagenic for all three kinds of polymorphisms. Finally, I present the program ILAPlot. It is a tool for visualisation, exploration and data extraction based on BLAST.Our combined results highlight the intricate connections between evolutionary phenomena. It also emphasises the importance of length variability in genome evolution, as well as the gradual difference between indels and microsatellites.
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