| 1. |
- 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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| 2. |
- Smith, Nick G C, et al.
(författare)
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A low rate of simultaneous double-nucleotide mutations in primates.
- 2003
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Ingår i: Molecular biology and evolution. - 0737-4038 .- 1537-1719. ; 20:1, s. 47-53
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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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| 3. |
- 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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| 4. |
- 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
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Ingår i: Genetics. - 0016-6731 .- 1943-2631. ; 164:1, s. 259-68
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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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| 5. |
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Webster, Matthew T, et al.
(författare)
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Compositional evolution of noncoding DNA in the human and chimpanzee genomes.
- 2003
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Ingår i: Molecular biology and evolution. - 0737-4038 .- 1537-1719. ; 20:2, s. 278-86
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the compositional evolution of noncoding DNA in the primate genome by comparison of lineage-specific substitutions observed in 1.8 Mb of genomic alignments of human, chimpanzee, and baboon with 6542 human single-nucleotide polymorphisms (SNPs) rooted using chimpanzee sequence. The pattern of compositional evolution, measured in terms of the numbers of GC-->AT and AT-->GC changes, differs significantly between fixed and polymorphic sites, and indicates that there is a bias toward fixation of AT-->GC mutations, which could result from weak directional selection or biased gene conversion in favor of high GC content. Comparison of the frequency distributions of a subset of the SNPs revealed no significant difference between GC-->AT and AT-->GC polymorphisms, although AT-->GC polymorphisms in regions of high GC segregate at slightly higher frequencies on average than GC-->AT polymorphisms, which is consistent with a fixation bias favoring high GC in these regions. However, the substitution data suggest that this fixation bias is relatively weak, because the compositional structure of the human and chimpanzee genomes is becoming homogenized, with regions of high GC decreasing in GC content and regions of low GC increasing in GC content. The rate and pattern of nucleotide substitution in 333 Alu repeats within the human-chimpanzee-baboon alignments are not significantly affected by the GC content of the region in which they are inserted, providing further evidence that, since the time of the human-chimpanzee ancestor, there has been little or no regional variation in mutation bias.
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| 9. |
- Webster, Matthew T., et al.
(författare)
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Compositional evolution of the human and chimpanzee genomes
- 2003
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 20:2, s. 278-286
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We have examined the compositional evolution of noncoding DNA in the primate genome by comparison of lineage-specific substitutions observed in 1.8 Mb of genomic alignments of human, chimpanzee, and baboon with 6542 human single-nucleotide polymorphisms (SNPs) rooted using chimpanzee sequence. The pattern of compositional evolution, measured in terms of the numbers of GC→AT and AT→GC changes, differs significantly between fixed and polymorphic sites, and indicates that there is a bias toward fixation of AT→GC mutations, which could result from weak directional selection or biased gene conversion in favor of high GC content. Comparison of the frequency distributions of a subset of the SNPs revealed no significant difference between GC→AT and AT→GC polymorphisms, although AT→GC polymorphisms in regions of high GC segregate at slightly higher frequencies on average than GC→AT polymorphisms, which is consistent with a fixation bias favoring high GC in these regions. However, the substitution data suggest that this fixation bias is relatively weak, because the compositional structure of the human and chimpanzee genomes is becoming homogenized, with regions of high GC decreasing in GC content and regions of low GC increasing in GC content. The rate and pattern of nucleotide substitution in 333 Alu repeats within the human-chimpanzee-baboon alignments are not significantly affected by the GC content of the region in which they are inserted, providing further evidence that, since the time of the human-chimpanzee ancestor, there has been little or no regional variation in mutation bias.
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| 10. |
- Webster, Matthew T., et al.
(författare)
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Gene expression, synteny, and local similarity in human noncoding mutation rates
- 2004
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 21:10, s. 1820-1830
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Tidskriftsartikel (refereegranskat)abstract
- The human genome is organized with regard to many features such as isochores, Giemsa bands, clusters of genes with similar expression patterns, and contiguous regions with shared evolutionary histories (synteny blocks). In addition to these genomic features, it is clear that mutation rates also vary across the human genome. To address how mutation rates and genomic features are related, we analyzed substitution rates at three classes of putatively neutral noncoding sites (nongenic, intronic, and ancestral repeats) in approximately 14 Mb of human-chimpanzee alignments covering human chromosome 7. Patterns of mutation rate variation inferred from substitution rate variation differ among the three site classes. In particular, we find that intronic mutation rates are strongly affected by the breadth of expression of the genes in which they reside, with broadly expressed genes exhibiting low mutation rates, probably as a consequence of the transcription-coupled repair process acting in the germ line. All site classes show significant local similarities in mutation rate at the megabase scale, and regional similarities in nongenic mutation rate covary with blocks of synteny between the human and mouse genomes, indicating that the evolutionary history of a genomic region is an important determinant of mutation rate.
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