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  • 1
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    High frequency of cryptic deleterious mutations in Caenorhabditis elegans (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-09-11
    Description: Deleterious mutations with very small phenotypic effects could be important for several evolutionary phenomena, but the extent of their contribution has been unknown. Fitness effects of induced mutations in lines of Caenorhabditis elegans were measured using a system for which the number of deleterious point mutations in the DNA can be estimated. In fitness assays, only about 4 percent of the deleterious mutations fixed in each line were detectable. The remaining 96 percent, though cryptic, are significant for mutation load and, potentially, for the evolution of sex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davies, E K -- Peters, A D -- Keightley, P D -- New York, N.Y. -- Science. 1999 Sep 10;285(5434):1748-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Cell, Animal and Population Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10481013" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*genetics/*physiology ; Computer Simulation ; Crosses, Genetic ; Disorders of Sex Development ; Ethyl Methanesulfonate/pharmacology ; *Genes, Helminth ; Likelihood Functions ; Models, Biological ; Models, Statistical ; Mutagens/pharmacology ; *Point Mutation ; Reproduction ; Selection, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Deleterious mutations and the evolution of sex (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-10-13
    Description: It has been suggested that sexual reproduction is maintained because it reduces the load imposed by recurrent deleterious mutations. If rates of deleterious mutation per diploid genome per generation (U) exceed 1, and mutations interact synergistically, then sexuals can overcome their inherent twofold disadvantage. We have tested this hypothesis by estimating genomic point mutation rates for protein-coding genes in a range of animal taxa. We find a positive linear relationship between U and generation time. In species with short generation times, U is predicted to be far below 1, suggesting that sex is not maintained by its capacity to purge the genome of deleterious mutations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keightley, P D -- Eyre-Walker, A -- New York, N.Y. -- Science. 2000 Oct 13;290(5490):331-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Cell, Animal and Population Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK. p.keightley@ed.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11030650" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Birds/genetics/physiology ; Cats/genetics/physiology ; Cattle/genetics/physiology ; DNA Transposable Elements ; Dogs/genetics/physiology ; Drosophila/genetics/physiology ; Female ; Haplorhini/genetics/physiology ; Humans ; Male ; Mutation ; *Point Mutation ; Proteins/genetics ; Rodentia/genetics/physiology ; *Sex ; Sheep/genetics/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-07-20
    Description: The mammalian protein MBD4 contains a methyl-CpG binding domain and can enzymatically remove thymine (T) or uracil (U) from a mismatched CpG site in vitro. These properties suggest that MBD4 might function in vivo to minimize the mutability of 5-methylcytosine by removing its deamination product from DNA. We tested this hypothesis by analyzing Mbd4-/- mice and found that the frequency of of C --〉 T transitions at CpG sites was increased by a factor of three. On a cancer-susceptible Apc(Min/+) background, Mbd4-/- mice showed accelerated tumor formation with CpG --〉 TpG mutations in the Apc gene. Thus MBD4 suppresses CpG mutability and tumorigenesis in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Millar, Catherine B -- Guy, Jacky -- Sansom, Owen J -- Selfridge, Jim -- MacDougall, Eilidh -- Hendrich, Brian -- Keightley, Peter D -- Bishop, Stefan M -- Clarke, Alan R -- Bird, Adrian -- New York, N.Y. -- Science. 2002 Jul 19;297(5580):403-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Centre for Cell Biology, The King's Buildings, Edinburgh University, Edinburgh EH9 3JR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12130785" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine ; Alleles ; Amino Acid Sequence ; Animals ; Base Pair Mismatch ; Cytosine/*analogs & derivatives/metabolism ; DNA Methylation ; DNA Repair ; Deamination ; Dinucleoside Phosphates/*genetics ; Endodeoxyribonucleases/*genetics/*physiology ; Female ; Gene Targeting ; Genes, APC ; Genetic Predisposition to Disease ; Intestinal Neoplasms/etiology/*genetics ; Intestine, Large ; Loss of Heterozygosity ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; *Point Mutation ; Suppression, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Functional constraints and frequency of deleterious mutations in noncoding DNA of rodents (2003)
    National Academy of Sciences
    Details
    Publication Date: 2003-11-03
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    New estimates of the rates and effects of mildly deleterious mutation in Drosophila melanogaster (1999)
    National Academy of Sciences
    Details
    Publication Date: 1999-01-19
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Recent Evolution in Rattus norvegicus Is Shaped by Declining Effective Population Size (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-22
    Description: The brown rat, Rattus norvegicus , is both a notorious pest and a frequently used model in biomedical research. By analyzing genome sequences of 12 wild-caught brown rats from their presumed ancestral range in NE China, along with the sequence of a black rat, Rattus rattus , we investigate the selective and demographic forces shaping variation in the genome. We estimate that the recent effective population size ( N e ) of this species = 1.24 x 105 , based on silent site diversity. We compare patterns of diversity in these genomes with patterns in multiple genome sequences of the house mouse ( Mus musculus castaneus ), which has a much larger N e . This reveals an important role for variation in the strength of genetic drift in mammalian genome evolution. By a Pairwise Sequentially Markovian Coalescent analysis of demographic history, we infer that there has been a recent population size bottleneck in wild rats, which we date to approximately 20,000 years ago. Consistent with this, wild rat populations have experienced an increased flux of mildly deleterious mutations, which segregate at higher frequencies in protein-coding genes and conserved noncoding elements. This leads to negative estimates of the rate of adaptive evolution ( α ) in proteins and conserved noncoding elements, a result which we discuss in relation to the strongly positive estimates observed in wild house mice. As a consequence of the population bottleneck, wild rats also show a markedly slower decay of linkage disequilibrium with physical distance than wild house mice.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans (1997)
    National Academy of Sciences
    Details
    Publication Date: 1997-04-15
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Nuclear Gene Variation in Wild Brown Rats (2012)
    Genetics Society of America (GSA)
    Details
    Publication Date: 2012-12-11
    Description: Although the brown rat ( Rattus norvegicus ) is widely used as a model mammal throughout biological sciences, little is known about genetic variation in wild rat populations or the relationship of commonly used inbred strains to their wild relatives. We sampled wild brown rats from the species’ presumed ancestral range in NW China and from a derived population in the UK and estimated nucleotide diversity and population subdivision, based on the sequences of 30 autosomal protein-coding loci. Neutral genetic diversity was close to 0.2% in both populations, which is about five times lower than diversity at the orthologous sites in a population of wild house mice from the species’ putative ancestral range in India. We found significant population differentiation between UK and Chinese populations, as assessed by F st and the program STRUCTURE. Based on synonymous diversity and divergence between the brown rat and house mouse, we estimate that the recent effective population size in brown rats is approximately 130,000 (approximate 95% confidence interval 85,000-184,000), about fivefold lower than wild house mice.
    Electronic ISSN: 2160-1836
    Topics: Biology
    Published by Genetics Society of America (GSA)
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  • 9
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    Direct Estimate of the Spontaneous Mutation Rate Uncovers the Effects of Drift and Recombination in the Chlamydomonas reinhardtii Plastid Genome (2016)
    Oxford University Press
    Details
    Publication Date: 2016-02-20
    Description: Plastids perform crucial cellular functions, including photosynthesis, across a wide variety of eukaryotes. Since endosymbiosis, plastids have maintained independent genomes that now display a wide diversity of gene content, genome structure, gene regulation mechanisms, and transmission modes. The evolution of plastid genomes depends on an input of de novo mutation, but our knowledge of mutation in the plastid is limited to indirect inference from patterns of DNA divergence between species. Here, we use a mutation accumulation experiment, where selection acting on mutations is rendered ineffective, combined with whole-plastid genome sequencing to directly characterize de novo mutation in Chlamydomonas reinhardtii. We show that the mutation rates of the plastid and nuclear genomes are similar, but that the base spectra of mutations differ significantly. We integrate our measure of the mutation rate with a population genomic data set of 20 individuals, and show that the plastid genome is subject to substantially stronger genetic drift than the nuclear genome. We also show that high levels of linkage disequilibrium in the plastid genome are not due to restricted recombination, but are instead a consequence of increased genetic drift. One likely explanation for increased drift in the plastid genome is that there are stronger effects of genetic hitchhiking. The presence of recombination in the plastid is consistent with laboratory studies in C. reinhardtii and demonstrates that although the plastid genome is thought to be uniparentally inherited, it recombines in nature at a rate similar to the nuclear genome.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    The Effect of Variation in the Effective Population Size on the Rate of Adaptive Molecular Evolution in Eukaryotes (2012)
    Oxford University Press
    Details
    Publication Date: 2012-06-12
    Description: The role of adaptation is a fundamental question in molecular evolution. Theory predicts that species with large effective population sizes should undergo a higher rate of adaptive evolution than species with low effective population sizes if adaptation is limited by the supply of mutations. Previous analyses have appeared to support this conjecture because estimates of the proportion of nonsynonymous substitutions fixed by adaptive evolution, α, tend to be higher in species with large N e . However, α is a function of both the number of advantageous and effectively neutral substitutions, either of which might depend on N e . Here, we investigate the relationship between N e and a , the rate of adaptive evolution relative to the rate of neutral evolution, using nucleotide polymorphism and divergence data from 13 independent pairs of eukaryotic species. We find a highly significant positive correlation between a and N e . We also find some evidence that the rate of adaptive evolution varies between groups of organisms for a given N e . The correlation between a and N e does not appear to be an artifact of demographic change or selection on synonymous codon use. Our results suggest that adaptation is to some extent limited by the supply of mutations and that at least some adaptation depends on newly occurring mutations rather than on standing genetic variation. Finally, we show that the proportion of nearly neutral nonadaptive substitutions declines with increasing N e . The low rate of adaptive evolution and the high proportion of effectively neutral substitution in species with small N e are expected to combine to make it difficult to detect adaptive molecular evolution in species with small N e .
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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