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Molecular Evolution of the Vertebrate Genome
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis, I studied molecular evolution of the vertebrate genome, focusing on sex chromosomes, protein coding genes, and genome size variation. The evolutionary history of avian sex chromosomes was analyzed by comparing substitution rate among 12 gametologous gene pairs on the Z and W chromosomes. Divergence estimates were distributed into three discrete clusters, evolutionary strata, implying stepwise cessations of recombination. Stratum 3 and stratum 2 are located the intervals 1-11Mb and 16-53Mb on the chicken Z chromosome, respectively. Stratum 1 was located in the middle of stratum 2, suggesting a chromosomal inversion. Using a molecular clock, the estimated times for cessation of recombination between Z and W are 132–150 (stratum 1), 71–99 (stratum 2), and 47–57 (stratum 3) million years ago.

Higher divergence rate in the Z chromosome than in autosomes (faster-Z) can be explained by positive selections on recessive alleles in hemizygous females, or by stronger genetic drift due to the smaller effective population size of the Z chromosomes. I found there was no difference in the intensity of the faster-Z effect among male-biased, female-biased, and unbiased genes, as might have been expected under a selection model. This result therefore supports the hypothesis that faster-Z is predominantly due to genetic drift.

Next, I analyzed molecular evolution of protein-coding genes in birds. In the comparison of zebra finch, chicken and non-avian outgroups, I found that neutral substitution rate was highest in zebra finch, intermediate in chicken, and lowest in ancestral birds. This difference seems attributable to differences in generation time, ancestral birds being most long-lived. Several functional categories were overrepresented among positively selected genes in avian lineages, such as transporter activity and calcium ion binding. I also found that many genes involved with cognitive processes including vocal learning were positively selected in zebra finch. I also found evidence for Hill-Robertson interference acting against the removal of slightly deleterious mutations at linked loci.

Finally, I studied the impact of recombination on genome size variation. I found that highly recombining regions have a more condensed genome structure, including shorter lengths of intron, intergenic spacer, transposable elements and higher gene density. In chicken and zebra finch I found that recombination rate was positively correlated with deletion bias, estimated by sequence comparisons between individual transposable elements (LINEs) and the corresponding master sequences. These observations indicate that the more compact genome structure in highly recombining region is due to a higher rate of sequence loss. Higher deletion bias in autosomes than in sex chromosomes supports this idea. I also found that sequence loss due to the deletion bias can explain nearly 20% of genome size reduction after the split of birds from other reptiles. In human, the recombination rate was positively correlated with the deletion bias estimated from polymorphic indels. These results support the hypothesis that the recombination drives genome contraction via the mutation process.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. , 49 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 935
National Category
Biological Sciences Evolutionary Biology Genetics
URN: urn:nbn:se:uu:diva-173400ISBN: 978-91-554-8373-9OAI: diva2:517366
Public defence
2012-06-08, ??, ??, 13:35 (English)
Available from: 2012-05-15 Created: 2012-04-23 Last updated: 2012-08-01Bibliographically approved
List of papers
1. The Chicken (Gallus gallus) Z Chromosome Contains at Least Three Nonlinear Evolutionary Strata
Open this publication in new window or tab >>The Chicken (Gallus gallus) Z Chromosome Contains at Least Three Nonlinear Evolutionary Strata
2008 (English)In: Genetics, ISSN 0016-6731, Vol. 180, no 2, 1131-1136 p.Article in journal (Refereed) Published
Abstract [en]

Birds have female heterogamety with Z and W sex chromosomes. These evolved from different autosomal precursor chromosomes than the mammalian X and Y However, previous work has suggested that the pattern and process of sex chromosome evolution show many similarities across distantly related organisms. Here we show that stepwise restriction of recombination between the protosex chromosomes of birds has resulted in regions of the chicken Z chromosome showing discrete levels of divergence from W homologs (gametologs). The 12 genes analyzed fall into three levels of estimated divergence values, with the most recent divergence (d(S) = 0.18-0.21) displayed by 6 genes in a region on the Z chromosome corresponding to the interval 1-11 Mb of the assembled genome sequence. Another 4 genes show intermediate divergence (d(S) = 0.27-0.38) and are located in the interval 16-53 Mb. Two genes (at positions 42 and 50 Mb) with higher values are located proximal to the most distal of the 4 genes with intermediate divergence, suggesting an inversion event. The distribution of genes and their divergence indicate at least three evolutionary strata, with estimated times for cessation of recombination between Z and Wof 132-150 (stratum 1), 71-99 (stratum 2), and 47-57 (stratum 3) million years ago. An inversion event, or some other form of intrachromosomal rearrangement, subsequent to the formation of strata 1 and 2 has scrambled the gene order to give rise to the nonlinear arrangement of evolutionary strata currently seen on the chicken Z chromosome. These observations suggest that the progressive restriction of recombination is an integral feature of sex chromosome evolution and occurs also in systems of female heterogamety.

National Category
Biological Sciences
urn:nbn:se:uu:diva-107824 (URN)10.1534/genetics.108.090324 (DOI)000260284400035 ()
Available from: 2009-08-31 Created: 2009-08-31 Last updated: 2012-08-01Bibliographically approved
2. Molecular evolution of genes in avian genomes
Open this publication in new window or tab >>Molecular evolution of genes in avian genomes
Show others...
2010 (English)In: Genome Biology, ISSN 1474-760X, Vol. 11, no 6, R68- p.Article in journal (Refereed) Published
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.

National Category
Developmental Biology
urn:nbn:se:uu:diva-134113 (URN)10.1186/gb-2010-11-6-r68 (DOI)000283775700011 ()
Available from: 2010-12-03 Created: 2010-11-22 Last updated: 2016-04-26
3. Recombination drives vertebrate genome contraction
Open this publication in new window or tab >>Recombination drives vertebrate genome contraction
2012 (English)In: PLOS Genetics, ISSN 1553-7390, Vol. 8, no 5, e1002680- p.Article in journal (Refereed) Published
Abstract [en]

Selective and/or neutral processes may govern variation in DNA content and, ultimately, genome size. The observation in several organisms of a negative correlation between recombination rate and intron size could be compatible with a neutral model in which recombination is mutagenic for length changes. We used whole-genome data on small insertions and deletions within transposable elements from chicken and zebra finch, to demonstrate clear links between recombination rate and a number of attributes of reduced DNA content. Recombination rate was negatively correlated with the length of introns, transposable elements and intergenic spacer, and the rate of short insertions. Importantly, it was positively correlated with gene density, the rate of short deletions, the deletion bias, and the net change in sequence length. All these observations point at a pattern of more condensed genome structure in regions of high recombination. Based on the observed rates of small insertions and deletions and assuming that these rates are representative for the whole genome, we estimate that the genome of the most recent common ancestor of birds and lizards have lost nearly 20% of its DNA content up till present. Expansion of transposable elements can counteract the effect of deletions in an equilibrium mutation model, however, since the activity of transposable elements has been low in the avian lineage, the deletion bias is likely to have had a significant effect on genome size evolution in dinosaurs and birds, contributing to the maintenance of a small genome. We also demonstrate that most of the observed correlations between recombination rate and genome contraction parameters are seen in the human genome, including for segregating indel polymorphisms. Our data are compatible with a neutral model in which recombination drive vertebrate genome size evolution and give no direct support for a role of natural selection in this process.

National Category
Genetics Bioinformatics and Systems Biology
urn:nbn:se:uu:diva-173276 (URN)10.1371/journal.pgen.1002680 (DOI)000304864000015 ()
Available from: 2012-04-23 Created: 2012-04-22 Last updated: 2012-08-06Bibliographically approved
4. Faster-Z evolution is predominantly due to genetic drift.
Open this publication in new window or tab >>Faster-Z evolution is predominantly due to genetic drift.
2010 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 27, no 3, 661-670 p.Article in journal (Refereed) Published
Abstract [en]

Genes linked to sex chromosomes may show different levels of functional change than autosomal genes due to different evolutionary pressures. We used whole-genome data from zebra finch-chicken orthologs to test for Faster-Z evolution, finding that Z-linked genes evolve up to 50% more rapidly than autosomal genes. We combined these divergence data with information about sex-specific expression patterns in order to determine whether the Faster-Z Effect that we observe was predominantly the result of positive selection of recessive beneficial mutations in the heterogametic sex or primarily due to genetic drift attributable to the lower effective population size of the Z chromosome compared with an autosome. The Faster-Z Effect was no more prevalent for genes expressed predominantly in females; therefore, our data indicate that the largest source of Faster-Z Evolution is the increased levels of genetic drift on the Z chromosome. This is likely a product of sexual selection acting on males, which reduces the effective population size of the Z relative to that of the autosomes. Additionally, this latter result suggests that the relative evolutionary pressures underlying Faster-Z Evolution are different from those in analogous Faster-X Evolution.

National Category
Biological Sciences
urn:nbn:se:uu:diva-136382 (URN)10.1098/rsbl.2008.0732< (DOI)000274786900015 ()19926635 (PubMedID)
Available from: 2010-12-13 Created: 2010-12-12 Last updated: 2016-04-26Bibliographically approved

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