| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 4. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 5. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 6. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 7. |
- Christmas, Matthew J, et al.
(författare)
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Chromosomal inversions associated with environmental adaptation in honeybees
- 2019
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Ingår i: Molecular Ecology. - : WILEY. - 0962-1083 .- 1365-294X. ; 28:6, s. 1358-1374
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal inversions can facilitate local adaptation in the presence of gene flow by suppressing recombination between well-adapted native haplotypes and poorly adapted migrant haplotypes. East African mountain populations of the honeybee Apis mellifera are highly divergent from neighbouring lowland populations at two extended regions in the genome, despite high similarity in the rest of the genome, suggesting that these genomic regions harbour inversions governing local adaptation. Here, we utilize a new highly contiguous assembly of the honeybee genome to characterize these regions. Using whole-genome sequencing data from 55 highland and lowland bees, we find that the highland haplotypes at both regions are present at high frequencies in three independent highland populations but extremely rare elsewhere. The boundaries of both divergent regions are characterized by regions of high homology with each other positioned in opposite orientations and contain highly repetitive, long inverted repeats with homology to transposable elements. These regions are likely to represent inversion breakpoints that participate in nonallelic homologous recombination. Using long-read data, we confirm that the lowland samples are contiguous across breakpoint regions. We do not find evidence for disruption of functional sequence by these breakpoints, which suggests that the inversions are likely maintained due to their allelic content conferring local adaptation in highland environments. Finally, we identify a third divergent genomic region, which contains highly divergent segregating haplotypes that also may contain inversion variants under selection. The results add to a growing body of evidence indicating the importance of chromosomal inversions in local adaptation.
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| 8. |
- Jones, Julia C., et al.
(författare)
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Extreme Differences in Recombination Rate between the Genomes of a Solitary and a Social Bee
- 2019
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 36:10, s. 2277-2291
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Tidskriftsartikel (refereegranskat)abstract
- Social insect genomes exhibit the highest rates of crossing over observed in plants and animals. The evolutionary causes of these extreme rates are unknown. Insight can be gained by comparing recombination rate variation across the genomes of related social and solitary insects. Here, we compare the genomic recombination landscape of the highly social honey bee, Apis mellifera, with the solitary alfalfa leafcutter bee, Megachile rotundata, by analyzing patterns of linkage disequilibrium in population-scale genome sequencing data. We infer that average recombination rates are extremely elevated in A. mellifera compared with M. rotundata. However, our results indicate that similar factors control the distribution of crossovers in the genomes of both species. Recombination rate is significantly reduced in coding regions in both species, with genes inferred to be germline methylated having particularly low rates. Genes with worker-biased patterns of expression in A. mellifera and their orthologs in M. rotundata have higher than average recombination rates in both species, suggesting that selection for higher diversity in genes involved in worker caste functions in social taxa is not the explanation for these elevated rates. Furthermore, we find no evidence that recombination has modulated the efficacy of selection among genes during bee evolution, which does not support the hypothesis that high recombination rates facilitated positive selection for new functions in social insects. Our results indicate that the evolution of sociality in insects likely entailed selection on modifiers that increased recombination rates genome wide, but that the genomic recombination landscape is determined by the same factors.
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| 9. |
- Rands, Chris M., et al.
(författare)
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Insights into the evolution of Darwin's finches from comparative analysis of the Geospiza magnirostris genome sequence
- 2013
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 14, s. 95-
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Tidskriftsartikel (refereegranskat)abstract
- Background: A classical example of repeated speciation coupled with ecological diversification is the evolution of 14 closely related species of Darwin's (Galapagos) finches (Thraupidae, Passeriformes). Their adaptive radiation in the Galapagos archipelago took place in the last 2-3 million years and some of the molecular mechanisms that led to their diversification are now being elucidated. Here we report evolutionary analyses of genome of the large ground finch, Geospiza magnirostris. Results: 13,291 protein-coding genes were predicted from a 991.0 Mb G. magnirostris genome assembly. We then defined gene orthology relationships and constructed whole genome alignments between the G. magnirostris and other vertebrate genomes. We estimate that 15% of genomic sequence is functionally constrained between G. magnirostris and zebra finch. Genic evolutionary rate comparisons indicate that similar selective pressures acted along the G. magnirostris and zebra finch lineages suggesting that historical effective population size values have been similar in both lineages. 21 otherwise highly conserved genes were identified that each show evidence for positive selection on amino acid changes in the Darwin's finch lineage. Two of these genes (Igf2r and Pou1f1) have been implicated in beak morphology changes in Darwin's finches. Five of 47 genes showing evidence of positive selection in early passerine evolution have cilia related functions, and may be examples of adaptively evolving reproductive proteins. Conclusions: These results provide insights into past evolutionary processes that have shaped G. magnirostris genes and its genome, and provide the necessary foundation upon which to build population genomics resources that will shed light on more contemporaneous adaptive and non-adaptive processes that have contributed to the evolution of the Darwin's finches.
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| 10. |
- Vaysse, Amaury, et al.
(författare)
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Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping
- 2011
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:10, s. e1002316-
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Tidskriftsartikel (refereegranskat)abstract
- The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.
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| 11. |
- Almén, Markus Sällman, et al.
(författare)
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Adaptive radiation of Darwin's finches revisited using whole genome sequencing
- 2016
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Ingår i: Bioessays. - : Wiley. - 0265-9247 .- 1521-1878. ; 38:1, s. 14-20
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Tidskriftsartikel (refereegranskat)abstract
- We recently used genome sequencing to study the evolutionary history of the Darwin's finches. A prominent feature of our data was that different polymorphic sites in the genome tended to indicate different genetic relationships among these closely related species. Such patterns are expected in recently diverged genomes as a result of incomplete lineage sorting. However, we uncovered conclusive evidence that these patterns have also been influenced by interspecies hybridisation, a process that has likely played an important role in the radiation of Darwin's finches. A major discovery was that segregation of two haplotypes at the ALX1 locus underlies variation in beak shape among the Darwin's finches, and that differences between the two haplotypes in a 240 kb region in blunt and pointed beaked birds involve both coding and regulatory changes. As we review herein, the evolution of such adaptive haplotypes comprising multiple causal changes appears to be an important mechanism contributing to the evolution of biodiversity.
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| 12. |
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| 13. |
- Axelsson, Erik, et al.
(författare)
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Comparison of the chicken and turkey genomes reveals a higher rate of nucleotide divergence on microchromosomes than macrochromosomes.
- 2005
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Ingår i: Genome Res. - 1088-9051. ; 15:1, s. 120-5
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Tidskriftsartikel (refereegranskat)abstract
- A distinctive feature of the avian genome is the large heterogeneity in the size of chromosomes, which are usually classified into a small number of macrochromosomes and numerous microchromosomes. These chromosome classes show characteristic differences in a number of interrelated features that could potentially affect the rate of sequence evolution, such as GC content, gene density, and recombination rate. We studied the effects of these factors by analyzing patterns of nucleotide substitution in two sets of chicken-turkey sequence alignments. First, in a set of 67 orthologous introns, divergence was significantly higher in microchromosomes (chromosomes 11-38; 11.7% divergence) than in both macrochromosomes (chromosomes 1-5; 9.9% divergence; P = 0.016) and intermediate-sized chromosomes (chromosomes 6-10; 9.5% divergence; P = 0.026). At least part of this difference was due to the higher incidence of CpG sites on microchromosomes. Second, using 155 orthologous coding sequences we noted a similar pattern, in which synonymous substitution rates on microchromosomes (13.1%) were significantly higher than were rates on macrochromosomes (10.3%; P = 0.024). Broadly assuming neutrality of introns and synonymous sites, or constraints on such sequences do not differ between chromosomal classes, these observations imply that microchromosomal genes are exposed to more germ line mutations than those on other chromosomes. We also find that dN/dS ratios for genes located on microchromosomes (average, 0.094) are significantly lower than those of macrochromosomes (average, 0.185; P = 0.025), suggesting that the proteins of genes on microchromosomes are under greater evolutionary constraint.
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| 14. |
- Axelsson, Erik, et al.
(författare)
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Death of PRDM9 coincides with stabilization of the recombination landscape in the dog genome
- 2011
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 22:1, s. 51-63
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of diverse eukaryotes has revealed that recombination events cluster in discrete genomic locations known as hotspots. In humans, a zinc-finger protein, PRDM9, is believed to initiate recombination in >40% of hotspots by binding to a specific DNA sequence motif. However, the PRDM9 coding sequence is disrupted in the dog genome assembly, raising questions regarding the nature and control of recombination in dogs. By analyzing the sequences of PRDM9 orthologs in a number of dog breeds and several carnivores, we show here that this gene was inactivated early in canid evolution. We next use patterns of linkage disequilibrium using more than 170,000 SNP markers typed in almost 500 dogs to estimate the recombination rates in the dog genome using a coalescent-based approach. Broad-scale recombination rates show good correspondence with an existing linkage-based map. Significant variation in recombination rate is observed on the fine scale, and we are able to detect over 4000 recombination hotspots with high confidence. In contrast to human hotspots, 40% of canine hotspots are characterized by a distinct peak in GC content. A comparative genomic analysis indicates that these peaks are present also as weaker peaks in the panda, suggesting that the hotspots have been continually reinforced by accelerated and strongly GC biased nucleotide substitutions, consistent with the long-term action of biased gene conversion on the dog lineage. These results are consistent with the loss of PRDM9 in canids, resulting in a greater evolutionary stability of recombination hotspots. The genetic determinants of recombination hotspots in the dog genome may thus reflect a fundamental process of relevance to diverse animal species.
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| 15. |
- Axelsson, Erik, et al.
(författare)
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The genomic signature of dog domestication reveals adaptation to a starch-rich diet
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 495:7441, s. 360-364
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Tidskriftsartikel (refereegranskat)abstract
- The domestication of dogs. was an important episode in the development of human civilization. The precise timing and location of this event is debated(1-5) and little is known about the genetic changes that accompanied the transformation of ancient wolves into domestic dogs. Here we conduct whole-genome resequencimg of dogs and wolves to identify 3.8 million genetic variants used to identify 36 genomic regions that probably represent targets for selection during dog domestication. Nineteen of these regions contain genes important in brain function, eight of which belong to nervous system development pathways and potentially underlie behavioural changes central to dog domestication(6). Ten genes with key roles in starch digestion and fat metabolism also show signals of selection. We identify candidate mutations in key genes and provide functional support for an increased starch digestion in dogs relative to wolves. Our results indicate that novel adaptations allowing the early ancestors of modern dogs to thrive on a diet rich in starch, relative to the carnivorous diet of wolves, constituted a crucial step in the early domestication of dogs.
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| 16. |
- Backström, Niclas, et al.
(författare)
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The recombination landscape of the zebra finch Taeniopygia guttata genome
- 2010
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 20:4, s. 485-495
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the causes and consequences of variation in the rate of recombination is essential since this parameter is considered to affect levels of genetic variability, the efficacy of selection, and the design of association and linkage mapping studies. However, there is limited knowledge about the factors governing recombination rate variation. We genotyped 1920 single nucleotide polymorphisms in a multigeneration pedigree of more than 1000 zebra finches (Taeniopygia guttata) to develop a genetic linkage map, and then we used these map data together with the recently available draft genome sequence of the zebra finch to estimate recombination rates in 1 Mb intervals across the genome. The average zebra finch recombination rate (1.5 cM/Mb) is higher than in humans, but significantly lower than in chicken. The local rates of recombination in chicken and zebra finch were only weakly correlated, demonstrating evolutionary turnover of the recombination landscape in birds. The distribution of recombination events was heavily biased toward ends of chromosomes, with a stronger telomere effect than so far seen in any organism. In fact, the recombination rate was as low as 0.1 cM/Mb in intervals up to 100 Mb long in the middle of the larger chromosomes. We found a positive correlation between recombination rate and GC content, as well as GC-rich sequence motifs. Levels of linkage disequilibrium (LD) were significantly higher in regions of low recombination, showing that heterogeneity in recombination rates have left a footprint on the genomic landscape of LD in zebra finch populations.
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| 17. |
- Bannasch, Danika, et al.
(författare)
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Localization of canine brachycephaly using an across breed mapping approach
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9632-
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Tidskriftsartikel (refereegranskat)abstract
- The domestic dog, Canis familiaris, exhibits profound phenotypic diversity and is an ideal model organism for the genetic dissection of simple and complex traits. However, some of the most interesting phenotypes are fixed in particular breeds and are therefore less tractable to genetic analysis using classical segregation-based mapping approaches. We implemented an across breed mapping approach using a moderately dense SNP array, a low number of animals and breeds carefully selected for the phenotypes of interest to identify genetic variants responsible for breed-defining characteristics. Using a modest number of affected (10-30) and control (20-60) samples from multiple breeds, the correct chromosomal assignment was identified in a proof of concept experiment using three previously defined loci; hyperuricosuria, white spotting and chondrodysplasia. Genome-wide association was performed in a similar manner for one of the most striking morphological traits in dogs: brachycephalic head type. Although candidate gene approaches based on comparable phenotypes in mice and humans have been utilized for this trait, the causative gene has remained elusive using this method. Samples from nine affected breeds and thirteen control breeds identified strong genome-wide associations for brachycephalic head type on Cfa 1. Two independent datasets identified the same genomic region. Levels of relative heterozygosity in the associated region indicate that it has been subjected to a selective sweep, consistent with it being a breed defining morphological characteristic. Genotyping additional dogs in the region confirmed the association. To date, the genetic structure of dog breeds has primarily been exploited for genome wide association for segregating traits. These results demonstrate that non-segregating traits under strong selection are equally tractable to genetic analysis using small sample numbers.
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| 18. |
- Belle, Elise M S, et al.
(författare)
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Why are young and old repetitive elements distributed differently in the human genome?
- 2005
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Ingår i: J Mol Evol. - 0022-2844. ; 60:3, s. 290-6
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Tidskriftsartikel (refereegranskat)abstract
- Alu elements are not distributed homogeneously throughout the human genome: old elements are preferentially found in the GC-rich parts of the genome, while young Alus are more often found in the GC-poor parts of the genome. The process giving rise to this differential distribution remains poorly understood. Here we investigate whether this pattern could be due to a preferential degradation of Alu elements integrated in GC-poor regions by small indel mutations. We aligned 5.1 Mb of human and chimpanzee sequences and examined whether the rate of insertion and deletion inside Alu elements differed according to the base composition surrounding them. We found that Alu elements are not preferentially degraded in GC-poor regions by indel events. We also looked at whether very young L1 elements show the same change in distribution compared to older ones. This analysis indicated that L1 elements also show a shift in their distribution, although we could not assess it as precisely as for Alu elements. We propose that the differential distribution of Alu elements is likely to be due to a change in their pattern of insertion or their probability of fixation through evolutionary time.
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| 19. |
- Berglund, Jonas, et al.
(författare)
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Germ line Methylation Patterns Determine the Distribution of Recombination Events in the Dog Genome
- 2015
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 7:2, s. 522-530
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Tidskriftsartikel (refereegranskat)abstract
- The positive-regulatory domain containing nine gene, PROMO, which strongly associates with the location of recombination events in several vertebrates, is inferred to be inactive in the dog genome. Here, we address several questions regarding the control of recombination and its influence on genome evolution in dogs. First, we address whether the association between CpG islands (CGIs) and recombination hotspots is generated by lack of methylation, GC-biased gene conversion (gBGC), or both. Using a genome-wide dog single nucleotide polymorphism data set and comparisons of the dog genome with related species, we show that recombination-associated CGIs have low CpG mutation rates, and that CpG mutation rate is negatively correlated with recombination rate genome wide, indicating that nonmethylation attracts the recombination machinery. We next use a neighbor-dependent model of nucleotide substitution to disentangle the effects of CpG mutability and gBGC and analyze the effects that loss of PROMO has on these rates. We infer that methylation patterns have been stable during canid genome evolution, but that dog CGIs have experienced a drastic increase in substitution rate due to gBGC, consistent with increased levels of recombination in these regions. We also show that gBGC is likely to have generated many new CGIs in the dog genome, but these mostly occur away from genes, whereas the number of C GIs in gene promoter regions has not increased greatly in recent evolutionary history. Recombination has a major impact on the distribution of CGIs that are detected in the dog genome due to the interaction between methylation and gBGC. The results indicate that germline methylation patterns are the main determinant of recombination rates in the absence of PRDM9.
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| 20. |
- Berglund, Jonas, et al.
(författare)
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Hotspots of biased nucleotide substitutions in human genes
- 2009
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 7:1, s. e26-
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Tidskriftsartikel (refereegranskat)abstract
- Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, we identified protein-coding sequences with an accelerated rate of base substitutions along the human lineage. Exons evolving at a fast rate in humans have a significant tendency to contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern is also observed in noncoding sequence flanking rapidly evolving exons. Accelerated exons occur in regions with elevated male recombination rates and exhibit an excess of nonsynonymous substitutions relative to the genomic average. We next analyzed genes with significantly elevated ratios of nonsynonymous to synonymous rates of base substitution (dN/dS) along the human lineage, and those with an excess of amino acid replacement substitutions relative to human polymorphism. These genes also show evidence of clusters of weak-to-strong biased substitutions. These findings indicate that a recombination-associated process, such as biased gene conversion (BGC), is driving fixation of GC alleles in the human genome. This process can lead to accelerated evolution in coding sequences and excess amino acid replacement substitutions, thereby generating significant results for tests of positive selection.
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| 21. |
- Berglund, Jonas, et al.
(författare)
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Novel origins of copy number variation in the dog genome
- 2012
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X .- 1474-7596. ; 13:8, s. R73-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. RESULTS: We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. CONCLUSIONS: A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9. These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution.
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| 22. |
- Björnerfeldt, Susanne, et al.
(författare)
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Relaxation of selective constraint on dog mitochondrial DNA following domestication
- 2006
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 16:8, s. 990-994
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Tidskriftsartikel (refereegranskat)abstract
- The domestication of dogs caused a dramatic change in their way of life compared with that of their ancestor, the gray wolf. We hypothesize that this new life style changed the selective forces that acted upon the species, which in turn had an effect on the dog's genome. We sequenced the complete mitochondrial DNA genome in 14 dogs, six wolves, and three coyotes. Here we show that dogs have accumulated nonsynonymous changes in mitochondrial genes at a faster rate than wolves, leading to elevated levels of variation in their proteins. This suggests that a major consequence of domestication in dogs was a general relaxation of selective constraint on their mitochondrial genome. If this change also affected other parts of the dog genome, it could have facilitated the generation of novel functional genetic diversity. This diversity could thus have contributed raw material upon which artificial selection has shaped modern breeds and may therefore be an important source of the extreme phenotypic variation present in modern-day dogs.
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| 23. |
- Borge, Thomas, et al.
(författare)
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Contrasting patterns of polymorphism and divergence on the Z chromosome and autosomes in two Ficedula flycatcher species
- 2005
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 171:4, s. 1861-1873
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Tidskriftsartikel (refereegranskat)abstract
- In geographic areas where pied and collared flycatchers (Ficedula hypoleuca and F. albicollis) breed in sympatry, hybridization occurs, leading to gene flow (introgression) between the two recently diverged species. Notably, while such introgression is observable at autosomal loci it is apparently absent at the Z chromosome, suggesting an important role for genes on the Z chromosome in creating reproductive isolation during speciation. To further understand the role of Z-linked loci in the formation of new species, we studied genetic variation of the two species from regions where they live in allopatry. We analyzed patterns of polymorphism and divergence in introns from 9 Z-linked and 23 autosomal genes in pied and collared flycatcher males. Average variation on the Z chromosome is greatly reduced compared to neutral expectations based on autosomal diversity in both species. We also observe significant heterogeneity between patterns of polymorphism and divergence at Z-linked loci and a relative absence of polymorphisms that are shared by the two species on the Z chromosome compared to the autosomes. We suggest that these observations may indicate the action of recurrent selective sweeps on the Z chromosome during the evolution of the two species, which may be caused by sexual selection acting on Z-linked genes. Alternatively, reduced variation on the Z chromosome could result from substantially higher levels of introgression at autosomal than at Z-linked loci or from a complex demographic history, such as a population bottleneck.
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| 24. |
- Cruz, F., et al.
(författare)
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The legacy of domestication : Accumulation of deleterious mutations in the dog genome
- 2008
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 25:11, s. 2331-2336
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Tidskriftsartikel (refereegranskat)abstract
- Dogs exhibit more phenotypic variation than any other mammal and are affected by a wide variety of genetic diseases. However, the origin and genetic basis of this variation is still poorly understood. We examined the effect of domestication on the dog genome by comparison with its wild ancestor, the gray wolf. We compared variation in dog and wolf genes using whole-genome single nucleotide polymorphism (SNP) data. The d(N)/d(S) ratio (omega) was around 50% greater for SNPs found in dogs than in wolves, indicating that a higher proportion of nonsynonymous alleles segregate in dogs compared with nonfunctional genetic variation. We suggest that the majority of these alleles are slightly deleterious and that two main factors may have contributed to their increase. The first is a relaxation of selective constraint due to a population bottleneck and altered breeding patterns accompanying domestication. The second is a reduction of effective population size at loci linked to those under positive selection due to Hill-Robertson interference. An increase in slightly deleterious genetic variation could contribute to the prevalence of disease in modern dog breeds.
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| 25. |
- Han, Fan, et al.
(författare)
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From where did the Western honeybee (Apis mellifera) originate?
- 2012
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 2:8, s. 1949-1957
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Tidskriftsartikel (refereegranskat)abstract
- The native range of the honeybee Apis mellifera encompasses Europe, Africa, and the Middle East, whereas the nine other species of Apis are found exclusively in Asia. It is therefore commonly assumed that A. mellifera arose in Asia and expanded into Europe and Africa. However, other hypotheses for the origin of A. mellifera have also been proposed based on phylogenetic trees constructed from genetic markers. In particular, an analysis based on >1000 single-nucleotide polymorphism markers placed the root of the tree of A. mellifera subspecies among samples from Africa, suggestive of an out-of-Africa expansion. Here, we re-evaluate the evidence for this and other hypotheses by testing the robustness of the tree topology to different tree-building methods and by removing specimens with a potentially hybrid background. These analyses do not unequivocally place the root of the tree of A. mellifera subspecies within Africa, and are potentially consistent with a variety of hypotheses for honeybee evolution, including an expansion out of Asia. Our analyses also support high divergence between western and eastern European populations of A. mellifera, suggesting they are likely derived from two distinct colonization routes, although the sources of these expansions are still unclear.
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| 26. |
- Lamichhaney, Sangeet, 1984-, et al.
(författare)
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A beak size locus in Darwin’s finches facilitated character displacement during a drought
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 352:6284, s. 470-474
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Tidskriftsartikel (refereegranskat)abstract
- Ecological character displacement is a process of morphological divergence that reducescompetition for limited resources. We used genomic analysis to investigate the geneticbasis of a documented character displacement event in Darwin’s finches on Daphne Majorin the Galápagos Islands: The medium ground finch diverged from its competitor, the largeground finch, during a severe drought. We discovered a genomic region containing theHMGA2gene that varies systematically among Darwin’s finch species with different beaksizes. Two haplotypes that diverged early in the radiation were involved in the characterdisplacement event: Genotypes associated with large beak size were at a strong selectivedisadvantage in medium ground finches (selection coefficients= 0.59). Thus, a majorlocus has apparently facilitated a rapid ecological diversification in the adaptive radiationof Darwin’s finches.
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| 27. |
- Lamichhaney, Sangeet, et al.
(författare)
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Evolution of Darwin's finches and their beaks revealed by genome sequencing
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7539
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Tidskriftsartikel (refereegranskat)abstract
- Darwin's finches, inhabiting the Galapagos archipelago and Cocos Island, constitute an iconic model for studies of speciation and adaptive evolution. Here we report the results of whole-genome re-sequencing of 120 individuals representing all of the Darwin's finch species and two close relatives' Phylogenetic analysis reveals important discrepancies with the phenotype-based taxonomy. We find extensive evidence for interspecific gene flow throughout the radiation. Hybridization has given rise to species of mixed ancestry. A 240 kilobase haplotype encompassing the ALX1 gene that encodes a transcription factor affecting craniofacial. development is strongly associated with beak shape diversity across Darwin's finch species as well as within the medium ground finch (Geospiza fortis) a species that has undergone rapid evolution of beak shape in response to environmental changes. The ALX1 haplotype has contributed to diversification of beak shapes among the Darwin's finches and thereby, to an expanded utilization of food resources.
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| 28. |
- Lamichhaney, Sangeet, et al.
(författare)
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Population-scale sequencing reveals genetic differentiation due to local adaptation in Atlantic herring
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:47, s. 19345-19350
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Tidskriftsartikel (refereegranskat)abstract
- The Atlantic herring (Clupea harengus), one of the most abundant marine fishes in the world, has historically been a critical food source in Northern Europe. It is one of the few marine species that can reproduce throughout the brackish salinity gradient of the Baltic Sea. Previous studies based on few genetic markers have revealed a conspicuous lack of genetic differentiation between geographic regions, consistent with huge population sizes and minute genetic drift. Here, we present a cost-effective genome-wide study in a species that lacks a genome sequence. We first assembled amuscle transcriptome and then aligned genomic reads to the transcripts, creating an "exome assembly," capturing both exons and flanking sequences. We then resequenced pools of fish from a wide geographic range, including the Northeast Atlantic, as well as different regions in the Baltic Sea, aligned the reads to the exome assembly, and identified 440,817 SNPs. The great majority of SNPs showed no appreciable differences in allele frequency among populations; however, several thousand SNPs showed striking differences, some approaching fixation for different alleles. The contrast between low genetic differentiation at most loci and striking differences at others implies that the latter category primarily reflects natural selection. A simulation study confirmed that the distribution of the fixation index F-ST deviated significantly from expectation for selectively neutral loci. This study provides insights concerning the population structure of an important marine fish and establishes the Atlantic herring as a model for population genetic studies of adaptation and natural selection.
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| 29. |
- Larson, Greger, et al.
(författare)
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Rethinking dog domestication by integrating genetics, archeology, and biogeography
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109, s. 8878-8883
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Tidskriftsartikel (refereegranskat)abstract
- The dog was the first domesticated animal but it remains uncertain when the domestication process began and whether it occurred just once or multiple times across the Northern Hemisphere. To ascertain the value of modern genetic data to elucidate the origins of dog domestication, we analyzed 49,024 autosomal SNPs in 1,375 dogs (representing 35 breeds) and 19 wolves. After combining our data with previously published data, we contrasted the genetic signatures of 121 breeds with a worldwide archeological assessment of the earliest dog remains. Correlating the earliest archeological dogs with the geographic locations of 14 so-called "ancient" breeds (defined by their genetic differentiation) resulted in a counterintuitive pattern. First, none of the ancient breeds derive from regions where the oldest archeological remains have been found. Second, three of the ancient breeds (Basenjis, Dingoes, and New Guinea Singing Dogs) come from regions outside the natural range of Canis lupus (the dog's wild ancestor) and where dogs were introduced more than 10,000 y after domestication. These results demonstrate that the unifying characteristic among all genetically distinct so-called ancient breeds is a lack of recent admixture with other breeds likely facilitated by geographic and cultural isolation. Furthermore, these genetically distinct ancient breeds only appear so because of their relative isolation, suggesting that studies of modern breeds have yet to shed light on dog origins. We conclude by assessing the limitations of past studies and how next-generation sequencing of modern and ancient individuals may unravel the history of dog domestication.
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| 30. |
- Liu, Yuanzhen, et al.
(författare)
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Genomic variation in montane bumblebees in Scandinavia : High levels of intraspecific diversity despite population vulnerability
- 2024
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Ingår i: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 33:4
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Tidskriftsartikel (refereegranskat)abstract
- Populations of many bumblebee species are declining, with distributions shifting northwards to track suitable climates. Climate change is considered a major contributing factor. Arctic species are particularly vulnerable as they cannot shift further north, making assessment of their population viability important. Analysis of levels of whole-genome variation is a powerful way to analyse population declines and fragmentation. Here, we use genome sequencing to analyse genetic variation in seven species of bumblebee from the Scandinavian mountains, including two classified as vulnerable. We sequenced 333 samples from across the ranges of these species in Sweden. Estimates of effective population size (NE) vary from ~55,000 for species with restricted high alpine distributions to 220,000 for more widespread species. Population fragmentation is generally very low or undetectable over large distances in the mountains, suggesting an absence of barriers to gene flow. The relatively high NE and low population structure indicate that none of the species are at immediate risk of negative genetic effects caused by high levels of genetic drift. However, reconstruction of historical fluctuations in NE indicates that the arctic specialist species Bombus hyperboreus has experienced population declines since the last ice age and we detected one highly inbred diploid male of this species close to the southern limit of its range, potentially indicating elevated genetic load. Although the levels of genetic variation in montane bumblebee populations are currently relatively high, their ranges are predicted to shrink drastically due to the effects of climate change and monitoring is essential to detect future population declines.
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| 31. |
- Mank, Judith E., et al.
(författare)
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The unique genomic properties of sex-biased genes: insights from avian microarray data
- 2008
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 9, s. 148-
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Tidskriftsartikel (refereegranskat)abstract
- Background: In order to develop a framework for the analysis of sex-biased genes, we present a characterization of microarray data comparing male and female gene expression in 18 day chicken embryos for brain, gonad, and heart tissue. Results: From the 15982 significantly expressed coding regions that have been assigned to either the autosomes or the Z chromosome ( 12979 in brain, 13301 in gonad, and 12372 in heart), roughly 18% were significantly sex- biased in any one tissue, though only 4 gene targets were biased in all tissues. The gonad was the most sex- biased tissue, followed by the brain. Sex- biased autosomal genes tended to be expressed at lower levels and in fewer tissues than unbiased gene targets, and autosomal somatic sex- biased genes had more expression noise than similar unbiased genes. Sex-biased genes linked to the Z- chromosome showed reduced expression in females, but not in males, when compared to unbiased Z- linked genes, and sex- biased Z- linked genes were also expressed in fewer tissues than unbiased Z coding regions. Third position GC content, and codon usage bias showed some sex- biased effects, primarily for autosomal genes expressed in the gonad. Finally, there were several over-represented Gene Ontology terms in the sex- biased gene sets. Conclusion: On the whole, this analysis suggests that sex- biased genes have unique genomic and organismal properties that delineate them from genes that are expressed equally in males and females.
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| 32. |
- Mausberg, Theresa-Bernadette, et al.
(författare)
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A Locus on Chromosome 5 Is Associated with Dilated Cardiomyopathy in Doberman Pinschers
- 2011
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Ingår i: PLoS One. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5, s. e20042-
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Tidskriftsartikel (refereegranskat)abstract
- Dilated cardiomyopathy (DCM) is a heterogeneous group of heart diseases with a strong genetic background. Currently, many human DCM cases exist where no causative mutation can be identified. DCM also occurs with high prevalence in several large dog breeds. In the Doberman Pinscher a specific DCM form characterized by arrhythmias and/or echocardiographic changes has been intensively studied by veterinary cardiologists. We performed a genome-wide association study in Doberman Pinschers. Using 71 cases and 70 controls collected in Germany we identified a genome-wide significant association to DCM on chromosome 5. We validated the association in an independent cohort collected in the United Kingdom. There is no known DCM candidate gene under the association signal. Therefore, DCM in Doberman Pinschers offers the chance of identifying a novel DCM gene that might also be relevant for human health.
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| 33. |
- Molin, Anna-Maja, et al.
(författare)
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Genome-wide copy number variant discovery in dogs using the CanineHD genotyping array
- 2014
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15, s. 210-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Substantial contribution to phenotypic diversity is accounted for by copy number variants (CNV). In human, as well as other species, the effect of CNVs range from benign to directly disease-causing which motivates the continued investigations of CNVs. Previous canine genome-wide screenings for CNVs have been performed using high-resolution comparative genomic hybridisation arrays which have contributed with a detailed catalogue of CNVs. Here, we present the first CNV investigation in dogs based on the recently reported CanineHD 170 K genotyping array. The hitherto largest dataset in canine CNV discovery was assessed, 351 dogs from 30 different breeds, enabling identification of novel CNVs and a thorough characterisation of breed-specific CNVs. Results: A stringent procedure identified 72 CNV regions with the smallest size of 38 kb and of the 72 CNV regions, 38 overlapped 148 annotated genes. A total of 29 novel CNV regions were found containing 44 genes. Furthermore, 15 breed specific CNV regions were identified of which 14 were novel and some of them overlapped putative disease susceptibility genes. In addition, the human ortholog of 23 canine copy number variable genes identified herein has been previously suggested to be dosage-sensitive in human. Conclusions: The present study evaluated the performance of the CanineHD in detecting CNVs and extends the current catalogue of canine CNV regions with several dozens of novel CNV regions. These novel CNV regions, which harbour candidate genes that possibly contribute to phenotypic variation in dogs or to disease-susceptibility, are a rich resource for future investigations.
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| 34. |
- Montero-Mendieta, Santiago, et al.
(författare)
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Phylogenomics and evolutionary history of Oreobates (Anura: Craugastoridae) Neotropical frogs along elevational gradients
- 2021
-
Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier. - 1055-7903 .- 1095-9513. ; 161
-
Tidskriftsartikel (refereegranskat)abstract
- Mountain ranges offer opportunities for understanding how species evolved and diversified across different environmental conditions. Neotropical frogs of the genus Oreobates (Anura: Craugastoridae) are adapted to highland and lowland habitats along the Andes, but many aspects of their evolution remain unknown. We studied their evolutionary history using ∼18,000 exons enriched by targeted sequence-capture. Since capture success was very variable across samples, we evaluated to what degree differing data filtering produced robust inferences. The inferred evolutionary framework evidenced phylogenetic discordances among lowland species that can be explained by taxonomic misidentification or admixture of ancestral lineages. Highland species showed smaller effective populations than lowland frogs, probably due to greater habitat fragmentation in montane environments. Stronger genetic drift likely decreased the power of purifying selection and led to an increased proportion of nonsynonymous mutations in highland populations that could play an important role in their adaptation. Overall, our work sheds light on the evolutionary history and diversification of this group of Neotropical frogs along elevational gradients in the Andes as well as on their patterns of intraspecific diversity.
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| 35. |
- Olsson, Mia, et al.
(författare)
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A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3, s. e1001332-
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (p(raw) = 2.3 x 10(-6), p(genome) = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p, < 0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation.
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| 36. |
- Owczarek-Lipska, Marta, et al.
(författare)
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Two Loci on Chromosome 5 Are Associated with Serum IgE Levels in Labrador Retrievers
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6, s. e39176-
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Tidskriftsartikel (refereegranskat)abstract
- Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response.
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| 37. |
- Ramirez, Oscar, et al.
(författare)
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Analysis of structural diversity in wolf-like canids reveals post-domestication variants
- 2014
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15, s. 465-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Although a variety of genetic changes have been implicated in causing phenotypic differences among dogs, the role of copy number variants (CNVs) and their impact on phenotypic variation is still poorly understood. Further, very limited knowledge exists on structural variation in the gray wolf, the ancestor of the dog, or other closely related wild canids. Documenting CNVs variation in wild canids is essential to identify ancestral states and variation that may have appeared after domestication. Results: In this work, we genotyped 1,611 dog CNVs in 23 wolf-like canids (4 purebred dogs, one dingo, 15 gray wolves, one red wolf, one coyote and one golden jackal) to identify CNVs that may have arisen after domestication. We have found an increase in GC-rich regions close to the breakpoints and around 1 kb away from them suggesting that some common motifs might be associated with the formation of CNVs. Among the CNV regions that showed the largest differentiation between dogs and wild canids we found 12 genes, nine of which are related to two known functions associated with dog domestication; growth (PDE4D, CRTC3 and NEB) and neurological function (PDE4D, EML5, ZNF500, SLC6A11, ELAVL2, RGS7 and CTSB). Conclusions: Our results provide insight into the evolution of structural variation in canines, where recombination is not regulated by PRDM9 due to the inactivation of this gene. We also identified genes within the most differentiated CNV regions between dogs and wolves, which could reflect selection during the domestication process.
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| 38. |
- Ratnakumar, Abhirami, et al.
(författare)
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Detecting positive selection within genomes : the problem of biased gene conversion
- 2010
-
Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 365:1552, s. 2571-2580
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Tidskriftsartikel (refereegranskat)abstract
- The identification of loci influenced by positive selection is a major goal of evolutionary genetics. A popular approach is to perform scans of alignments on a genome-wide scale in order to find regions evolving at accelerated rates on a particular branch of a phylogenetic tree. However, positive selection is not the only process that can lead to accelerated evolution. Notably, GC-biased gene conversion (gBGC) is a recombination-associated process that results in the biased fixation of G and C nucleotides. This process can potentially generate bursts of nucleotide substitutions within hotspots of meiotic recombination. Here, we analyse the results of a scan for positive selection on genes on branches across the primate phylogeny. We show that genes identified as targets of positive selection have a significant tendency to exhibit the genomic signature of gBGC. Using a maximum-likelihood framework, we estimate that more than 20 per cent of cases of significantly elevated non-synonymous to synonymous substitution rates ratio (d(N)/d(S)), particularly in shorter branches, could be due to gBGC. We demonstrate that in some cases, gBGC can lead to very high d(N)/d(S) (more than 2). Our results indicate that gBGC significantly affects the evolution of coding sequences in primates, often leading to patterns of evolution that can be mistaken for positive selection.
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| 39. |
- Rubin, Carl-Johan, et al.
(författare)
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Whole genome resequencing reveals loci under selection during chicken domestication
- 2010
-
Ingår i: Nature. - London : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7288, s. 587-591
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Tidskriftsartikel (refereegranskat)abstract
- Domestic animals are excellent models for genetic studies of phenotypic evolution. They have evolved genetic adaptations to a new environment, the farm, and have been subjected to strong human-driven selection leading to remarkable phenotypic changes in morphology, physiology and behaviour. Identifying the genetic changes underlying these developments provides new insight into general mechanisms by which genetic variation shapes phenotypic diversity. Here we describe the use of massively parallel sequencing to identify selective sweeps of favourable alleles and candidate mutations that have had a prominent role in the domestication of chickens (Gallus gallus domesticus) and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens. We have generated 44.5-fold coverage of the chicken genome using pools of genomic DNA representing eight different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor. We report more than 7,000,000 single nucleotide polymorphisms, almost 1,300 deletions and a number of putative selective sweeps. One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates. Several of the selective sweeps detected in broilers overlapped genes associated with growth, appetite and metabolic regulation. We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important. This study has direct application to animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research.
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| 40. |
- Seppala, Eija H., et al.
(författare)
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LGI2 Truncation Causes a Remitting Focal Epilepsy in Dogs
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:7, s. e1002194-
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Tidskriftsartikel (refereegranskat)abstract
- One quadrillion synapses are laid in the first two years of postnatal construction of the human brain, which are then pruned until age 10 to 500 trillion synapses composing the final network. Genetic epilepsies are the most common neurological diseases with onset during pruning, affecting 0.5% of 2-10-year-old children, and these epilepsies are often characterized by spontaneous remission. We previously described a remitting epilepsy in the Lagotto romagnolo canine breed. Here, we identify the gene defect and affected neurochemical pathway. We reconstructed a large Lagotto pedigree of around 34 affected animals. Using genome-wide association in 11 discordant sib-pairs from this pedigree, we mapped the disease locus to a 1.7 Mb region of homozygosity in chromosome 3 where we identified a protein-truncating mutation in the Lgi2 gene, a homologue of the human epilepsy gene LGI1. We show that LGI2, like LGI1, is neuronally secreted and acts on metalloproteinase-lacking members of the ADAM family of neuronal receptors, which function in synapse remodeling, and that LGI2 truncation, like LGI1 truncations, prevents secretion and ADAM interaction. The resulting epilepsy onsets at around seven weeks (equivalent to human two years), and remits by four months (human eight years), versus onset after age eight in the majority of human patients with LGI1 mutations. Finally, we show that Lgi2 is expressed highly in the immediate post-natal period until halfway through pruning, unlike Lgi1, which is expressed in the latter part of pruning and beyond. LGI2 acts at least in part through the same ADAM receptors as LGI1, but earlier, ensuring electrical stability (absence of epilepsy) during pruning years, preceding this same function performed by LGI1 in later years. LGI2 should be considered a candidate gene for common remitting childhood epilepsies, and LGI2-to-LGI1 transition for mechanisms of childhood epilepsy remission.
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| 41. |
- Smith, Nick G C, et al.
(författare)
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A low rate of simultaneous double-nucleotide mutations in primates.
- 2003
-
Ingår i: Molecular biology and evolution. - 0737-4038 .- 1537-1719. ; 20:1, s. 47-53
-
Tidskriftsartikel (refereegranskat)abstract
- The occurrence of double-nucleotide (doublet) mutations is contrary to the normal assumption that point mutations affect single nucleotides. Here we develop a new method for estimating the doublet mutation rate and apply it to more than a megabase of human-chimpanzee-baboon genomic DNA alignments and more than a million human single-nucleotide polymorphisms. The new method accounts for the effect of regional variation in evolutionary rates, which may be a confounding factor in previous estimates of the doublet mutation rate. Furthermore we determine sequence context effects by using sequence comparisons over a variety of lineage lengths. This approach yields a new estimate of the doublet mutation rate of 0.3% of the singleton rate, indicating that doublet mutations are far rarer than previously thought. Our results suggest that doublet mutations are unlikely to have caused the correlation between synonymous and nonsynonymous substitution rates in mammals, and also show that regional variation and sequence context effects play an important role in primate DNA sequence evolution.
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| 42. |
- Smith, Nick G C, et al.
(författare)
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Deterministic mutation rate variation in the human genome.
- 2002
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 12:9, s. 1350-6
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Tidskriftsartikel (refereegranskat)abstract
- Several studies of substitution rate variation have indicated that the local mutation rate varies over the mammalian genome. In the present study, we show significant variation in substitution rates within the noncoding part of the human genome using 4.7 Mb of human-chimpanzee pairwise comparisons. Moreover, we find a significant positive covariation of lineage-specific chimpanzee and human local substitution rates, and very similar mean substitution rates down the two lineages. The substitution rate variation is probably not caused by selection or biased gene conversion, and so we conclude that mutation rates vary deterministically across the noncoding nonrepetitive regions of the human genome. We also show that noncoding substitution rates are significantly affected by G+C base composition, partly because the base composition is not at equilibrium.
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| 43. |
- Sundström, Hannah, et al.
(författare)
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Is the rate of insertion and deletion mutation male biased? : Molecular evolutionary analysis of avian and primate sex chromosome sequences.
- 2003
-
Ingår i: Genetics. - 0016-6731 .- 1943-2631. ; 164:1, s. 259-68
-
Tidskriftsartikel (refereegranskat)abstract
- The rate of mutation for nucleotide substitution is generally higher among males than among females, likely owing to the larger number of DNA replications in spermatogenesis than in oogenesis. For insertion and deletion (indel) mutations, data from a few human genetic disease loci indicate that the two sexes may mutate at similar rates, possibly because such mutations arise in connection with meiotic crossing over. To address origin- and sex-specific rates of indel mutation we have conducted the first large-scale molecular evolutionary analysis of indels in noncoding DNA sequences from sex chromosomes. The rates are similar on the X and Y chromosomes of primates but about twice as high on the avian Z chromosome as on the W chromosome. The fact that indels are not uncommon on the nonrecombining Y and W chromosomes excludes meiotic crossing over as the main cause of indel mutation. On the other hand, the similar rates on X and Y indicate that the number of DNA replications (higher for Y than for X) is also not the main factor. Our observations are therefore consistent with a role of both DNA replication and recombination in the generation of short insertion and deletion mutations. A significant excess of deletion compared to insertion events is observed on the avian W chromosome, consistent with gradual DNA loss on a nonrecombining chromosome.
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| 44. |
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| 45. |
- Sundström, Hannah, et al.
(författare)
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Reduced variation on the chicken Z chromosome
- 2004
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 167:1, s. 377-385
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the population genetic factors that shape genome variability is pivotal to the design and interpretation of studies using large-scale polymorphism data. We analyzed patterns of polymorphism and divergence at Z-linked and autosomal loci in the domestic chicken (Gallus gallus) to study the influence of mutation, effective population size, selection, and demography on levels of genetic diversity. A total of 14 autosomal introns (8316 bp) and 13 Z-linked introns (6856 bp) were sequenced in 50 chicken chromosomes from 10 highly divergent breeds. Genetic variation was significantly lower at Z-linked than at autosomal loci, with one segregating site every 39 bp at autosomal loci (θW = 5.8 ± 0.8 × 10–3) and one every 156 bp on the Z chromosome (θW = 1.4 ± 0.4 × 10–3). This difference may in part be due to a low male effective population size arising from skewed reproductive success among males, evident both in the wild ancestor—the red jungle fowl—and in poultry breeding. However, this effect cannot entirely explain the observed three- to fourfold reduction in Z chromosome diversity. Selection, in particular selective sweeps, may therefore have had an impact on reducing variation on the Z chromosome, a hypothesis supported by the observation of heterogeneity in diversity levels among loci on the Z chromosome and the lower recombination rate on Z than on autosomes. Selection on sex-linked genes may be particularly important in organisms with female heterogamety since the heritability of sex-linked sexually antagonistic alleles advantageous to males is improved when fathers pass a Z chromosome to their sons.
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| 46. |
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| 47. |
- Wallberg, Andreas, et al.
(författare)
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A worldwide survey of genome sequence variation provides insight into the evolutionary history of the honeybee Apis mellifera
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:10, s. 1081-1088
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Tidskriftsartikel (refereegranskat)abstract
- The honeybee Apis mellifera has major ecological and economic importance. We analyze patterns of genetic variation at 8.3 million SNPs, identified by sequencing 140 honeybee genomes from a worldwide sample of 14 populations at a combined total depth of 634×. These data provide insight into the evolutionary history and genetic basis of local adaptation in this species. We find evidence that population sizes have fluctuated greatly, mirroring historical fluctuations in climate, although contemporary populations have high genetic diversity, indicating the absence of domestication bottlenecks. Levels of genetic variation are strongly shaped by natural selection and are highly correlated with patterns of gene expression and DNA methylation. We identify genomic signatures of local adaptation, which are enriched in genes expressed in workers and in immune system- and sperm motility-related genes that might underlie geographic variation in reproduction, dispersal and disease resistance. This study provides a framework for future investigations into responses to pathogens and climate change in honeybees.
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| 48. |
- Wallberg, Andreas, et al.
(författare)
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Extreme Recombination Frequencies Shape Genome Variation and Evolution in the Honeybee, Apis mellifera
- 2015
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Meiotic recombination is a fundamental cellular process, with important consequences for evolution and genome integrity. However, we know little about how recombination rates vary across the genomes of most species and the molecular and evolutionary determinants of this variation. The honeybee, Apis mellifera, has extremely high rates of meiotic recombination, although the evolutionary causes and consequences of this are unclear. Here we use patterns of linkage disequilibrium in whole genome resequencing data from 30 diploid honeybees to construct a fine-scale map of rates of crossing over in the genome. We find that, in contrast to vertebrate genomes, the recombination landscape is not strongly punctate. Crossover rates strongly correlate with levels of genetic variation, but not divergence, which indicates a pervasive impact of selection on the genome. Germ-line methylated genes have reduced crossover rate, which could indicate a role of methylation in suppressing recombination. Controlling for the effects of methylation, we do not infer a strong association between gene expression patterns and recombination. The site frequency spectrum is strongly skewed from neutral expectations in honeybees: rare variants are dominated by AT-biased mutations, whereas GC-biased mutations are found at higher frequencies, indicative of a major influence of GC-biased gene conversion (gBGC), which we infer to generate an allele fixation bias 5 - 50 times the genomic average estimated in humans. We uncover further evidence that this repair bias specifically affects transitions and favours fixation of CpG sites. Recombination, via gBGC, therefore appears to have profound consequences on genome evolution in honeybees and interferes with the process of natural selection. These findings have important implications for our understanding of the forces driving molecular evolution.
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| 49. |
- Wallberg, Andreas, et al.
(författare)
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Identification of Multiple Loci Associated with Social Parasitism in Honeybees
- 2016
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- In colonies of the honeybee Apis mellifera, the queen is usually the only reproductive female, which produces new females (queens and workers) by laying fertilized eggs. However, in one subspecies of A. mellifera, known as the Cape bee (A. m. capensis), worker bees reproduce asexually by thelytoky, an abnormal form of meiosis where two daughter nucleii fuse to form single diploid eggs, which develop into females without being fertilized. The Cape bee also exhibits a suite of phenotypes that facilitate social parasitism whereby workers lay such eggs in foreign colonies so their offspring can exploit their resources. The genetic basis of this switch to social parasitism in the Cape bee is unknown. To address this, we compared genome variation in a sample of Cape bees with other African populations. We find genetic divergence between these populations to be very low on average but identify several regions of the genome with extreme differentiation. The regions are strongly enriched for signals of selection in Cape bees, indicating that increased levels of positive selection have produced the unique set of derived phenotypic traits in this subspecies. Genetic variation within these regions allows unambiguous genetic identification of Cape bees and likely underlies the genetic basis of social parasitism. The candidate loci include genes involved in ecdysteroid signaling and juvenile hormone and dopamine biosynthesis, which may regulate worker ovary activation and others whose products localize at the centrosome and are implicated in chromosomal segregation during meiosis. Functional analysis of these loci will yield insights into the processes of reproduction and chemical signaling in both parasitic and non-parasitic populations and advance understanding of the process of normal and atypical meiosis.
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| 50. |
- Webster, Matthew T, et al.
(författare)
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Analysis of variation in the human beta-globin gene cluster using a novel DHPLC technique.
- 2002
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Ingår i: Mutation research. - 0027-5107 .- 1873-135X. ; 501:1-2, s. 99-103
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Tidskriftsartikel (refereegranskat)abstract
- We have implemented a technique combining allele-specific PCR (AS-PCR) and denaturing high-performance liquid chromatography (DHPLC) to identify new polymorphic variants within an intergenic region in the beta-globin cluster. This technique is applicable to the detection of new variants in genomic regions where variation is apportioned into distinct classes of haplotype. Duplexes for DHPLC analysis were created by denaturation and re-annealing of a mixture of two AS-PCR products of known and unknown sequence from the same haplotypic class, permitting detection of new haplotypes in each class. A 454bp fragment 3.5kb 5' to the human delta-globin gene, which may have a gene regulatory function, was analysed in 840 chromosomes from a global sampling of human populations using this method. Two divergent haplotypes were found to predominate in all populations studied, possibly as a result of balancing selection.
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