High Spontaneous Rate of Gene Duplication in Caenorhabditis elegans

Lipinski, Kendra J.; Farslow, James C.; Fitzpatrick, Kelly A.; Lynch, Michael; Katju, Vaishali; Bergthorsson, Ulfar

doi:10.1016/j.cub.2011.01.026

Cited by 116 publications

(153 citation statements)

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“…Recent mutation rate estimates in humans (Itsara et al 2010), S. cerevisiae (Lynch et al 2008), and C. elegans (Lipinski et al 2011) all show an excess of duplicated relative to deleted base pairs. CNVs with allele frequencies ,0.1 from a natural population of D. melanogaster from Raleigh, North Carolina, also reveal a similar 2:1 excess of duplicated sequence (Langley et al 2012).…”

Section: Mutation Rate Estimates For Large Duplications and Deletionsmentioning

confidence: 99%

“…We compared these results to those from two previous studies that were able to estimate the rates of gene duplications and deletions with low-resolution array-based techniques, one in C. elegans (Lipinski et al 2011) and one in S. cerevisiae (Lynch et al 2008). Our estimates of these rates in Drosophila are somewhat higher than those observed in C. elegans (2.2 · 10 27 partially deleted genes/gene/generation; 3.4 · 10 27 partially duplicated genes/gene/generation, according to Lipinski et al 2011), but lower than the rates estimated in S. cerevisiae (3.4 · 10 26 duplicated genes/gene/generation; 2.1 · 10 26 deleted genes/gene/generation, according to Lynch et al 2008). In all three data sets, however, the rate at which new genic copy-number mutations arise is quite high, with approximately one whole-gene duplicate arising per haploid genome every 50-500 generations.…”

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confidence: 99%

“…It is therefore essential for our understanding of the rate of adaptive evolution and the origin of genomic disorders that we accurately measure the spontaneous rates of these mutations. Although several studies examining either MA lines (Lynch et al 2008;Ossowski et al 2010;Lipinski et al 2011) or human parent-offspring trios (Itsara et al 2010) have been able to estimate the rate of large duplication and deletion events, these studies were able to reliably detect events only several kilobases in length due to their reliance on low-resolution detection methods (e.g., microarray hybridization, sequence read depth, or pulsed-field gel electrophoresis).…”

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Rates and Genomic Consequences of Spontaneous Mutational Events inDrosophila melanogaster

et al. 2013

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Because spontaneous mutation is the source of all genetic diversity, measuring mutation rates can reveal how natural selection drives patterns of variation within and between species. We sequenced eight genomes produced by a mutation-accumulation experiment in Drosophila melanogaster. Our analysis reveals that point mutation and small indel rates vary significantly between the two different genetic backgrounds examined. We also find evidence that 2% of mutational events affect multiple closely spaced nucleotides. Unlike previous similar experiments, we were able to estimate genome-wide rates of large deletions and tandem duplications. These results suggest that, at least in inbred lines like those examined here, mutational pressures may result in net growth rather than contraction of the Drosophila genome. By comparing our mutation rate estimates to polymorphism data, we are able to estimate the fraction of new mutations that are eliminated by purifying selection. These results suggest that 99% of duplications and deletions are deleterious-making them 10 times more likely to be removed by selection than nonsynonymous mutations. Our results illuminate not only the rates of new small-and large-scale mutations, but also the selective forces that they encounter once they arise.B ECAUSE all genetic variation on which natural selection acts originates via spontaneous mutation, the rate at which various types of mutations appear in natural populations has important consequences for the manner in which organisms evolve. Once we determine the rate at which adaptive and deleterious alleles arise, we can understand how natural selection shapes the spectrum of variation within and between species (Lynch et al. 2008). Mutationaccumulation (MA) experiments are the most widely used method for directly measuring spontaneous mutation rates (Halligan and Keightley 2009). In these experiments genetically identical individuals are subdivided into initially homogeneous sublines, and these sublines are maintained over many generations. At each generation a minimum number of individuals are randomly selected to reproduce and propagate the MA subline, thereby limiting the ability of natural selection to purge new deleterious mutations or to favor new adaptive alleles. Because the MA sublines are initially identical (barring any contamination or residual heterozygosity), any genetic differences among lines must arise via mutations occurring during the course of the experiment.Mutation-accumulation experiments were initially used to assess the phenotypic impacts of mutation (e.g., Mukai et al. 1972). More recently, mutation-accumulation has been used to assess the rate of spontaneous mutation on the genome at specific loci (Mukai and Cockerham 1977), selected genomic regions (Haag-Liautard et al. 2007), or, with the advent of next-generation sequencing technology, genome-wide. Mutation accumulation is now used to estimate genome-wide estimates of per-site mutation rates in a variety of eukaryotes, including Saccharomyces cerevis...

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Section: Mutation Rate Estimates For Large Duplications and Deletionsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Rates and Genomic Consequences of Spontaneous Mutational Events inDrosophila melanogaster

et al. 2013

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“…Surprisingly, it revealed that gene duplications and deletions are probably more frequent than substitutions (Katju & Lynch, 2003; Lipinski et al., 2011; Lynch et al., 2008; Schrider, Houle, Lynch, & Hahn, 2013). Copy‐number variations (CNV) are indeed ubiquitous in natural populations (e.g., Freeman et al., 2006).…”

Section: Introductionmentioning

confidence: 99%

Adaptive deletion in resistance gene duplications in the malaria vector Anopheles gambiae

Assogba

Alout

Koffi

et al. 2018

Evolutionary Applications

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While gene copy‐number variations play major roles in long‐term evolution, their early dynamics remains largely unknown. However, examples of their role in short‐term adaptation are accumulating: identical repetitions of a locus (homogeneous duplications) can provide a quantitative advantage, while the association of differing alleles (heterogeneous duplications) allows carrying two functions simultaneously. Such duplications often result from rearrangements of sometimes relatively large chromosome fragments, and even when adaptive, they can be associated with deleterious side effects that should, however, be reduced by subsequent evolution. Here, we took advantage of the unique model provided by the malaria mosquito Anopheles gambiae s.l. to investigate the early evolution of several duplications, heterogeneous and homogeneous, segregating in natural populations from West Africa. These duplications encompass ~200 kb and 11 genes, including the adaptive insecticide resistance ace‐1 locus. Through the survey of several populations from three countries over 3–4 years, we showed that an internal deletion of all coamplified genes except ace‐1 is currently spreading in West Africa and introgressing from An. gambiae s.s. to An. coluzzii. Both observations provide evidences of its selection, most likely due to reducing the gene‐dosage disturbances caused by the excessive copies of the nonadaptive genes. Our study thus provides a unique example of the early adaptive trajectory of duplications and underlines the role of the environmental conditions (insecticide treatment practices and species ecology). It also emphasizes the striking diversity of adaptive responses in these mosquitoes and reveals a worrisome process of resistance/cost trade‐off evolution that could impact the control of malaria vectors in Africa.

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“…Five lines were identified from each tail of the fitness distribution of a set of~70 MA lines that accumulated mutations for 250 generations; on average, the five 'high fitness' MA lines have threefold higher fitness than the five 'low fitness' lines (Matsuba et al, 2012). Various lines of evidence suggest that the per-genome mutation rate in the base population is unlikely to be much less than one-half nor more than about two per generation (Denver et al, 2004;Phillips et al, 2009;Lipinski et al, 2011;Denver et al, 2012). Provided that the distribution of mutations among lines is Poisson (the standard assumption), it is very unlikely that the different sets of lines differ by nearly as much as threefold in the number of mutations unless the mutation rate itself has evolved.…”

Section: Introductionmentioning

confidence: 99%

Abiotic stress does not magnify the deleterious effects of spontaneous mutations

et al. 2015

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Although the effects of deleterious alleles often are predicted to be greater in stressful environments, there is no theoretical basis for this prediction and the empirical evidence is mixed. Here we characterized the effects of three types of abiotic stress (thermal, oxidative and hyperosmotic) on two sets of nematode (Caenorhabditis elegans) mutation accumulation (MA) lines that differ by threefold in fitness. We compared the survival and egg-to-adult viability between environments (benign and stressful) and between fitness categories (high-fitness MA, low-fitness MA). If the environment and mutation load have synergistic effects on trait means, then the difference between the high and low-fitness MA lines should be larger in stressful environments. Although the stress treatments consistently decreased survival and/or viability, we did not detect significant interactions between fitness categories and environment types. In contrast, we did find consistent evidence for synergistic effects on (micro) environmental variation. The lack of signal in trait means likely reflects the very low starting fitness of some low-fitness MA lines, the potential for cross-stress responses and the context dependence of mutational effects. In addition, the large increases in the environmental variance in the stressful environments may have masked small changes in trait means. These results do not provide evidence for synergism between mutation and stress.

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High Spontaneous Rate of Gene Duplication in Caenorhabditis elegans

Cited by 116 publications

References 41 publications

Rates and Genomic Consequences of Spontaneous Mutational Events inDrosophila melanogaster

Rates and Genomic Consequences of Spontaneous Mutational Events inDrosophila melanogaster

Adaptive deletion in resistance gene duplications in the malaria vector Anopheles gambiae

Abiotic stress does not magnify the deleterious effects of spontaneous mutations

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