Estimation of microsatellite mutation rates in Drosophila melanogaster

Microsatellite mutations were studied in a set of 175 mutation accumulation lines, all of them independently derived from a completely homozygous population of Drosophila melanogaster and maintained under strong inbreeding during 80 generations. We assayed 28 microsatellites and detected two mutations. One mutation consisted of a single addition of a dinucleotide repeat and the other was a deletion of five trinucleotide repeats. The average mutation rate was 5·1 × 10−6, in full agreement with previous estimates from two different sets of mutation accumulation lines.

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Y-chromosomal microsatellite mutation rates: Differences in mutation rate between and within loci

Human Mutation ◽

10.1002/humu.10294 ◽

2004 ◽

Vol 23 (2) ◽

pp. 117-124 ◽

Cited By ~ 82

Author(s):

B. Myhre Dupuy ◽

M. Stenersen ◽

T. Egeland ◽

B. Olaisen

Keyword(s):

Mutation Rate ◽

Mutation Rates ◽

Microsatellite Mutation

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First Estimation of the Spontaneous Mutation Rate in Diatoms

Genome Biology and Evolution ◽

10.1093/gbe/evz130 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1829-1837 ◽

Cited By ~ 11

Author(s):

Marc Krasovec ◽

Sophie Sanchez-Brosseau ◽

Gwenael Piganeau

Keyword(s):

Mutation Rate ◽

Spontaneous Mutation ◽

Mutation Accumulation ◽

Mutation Rates ◽

Model Organisms ◽

Base Substitution ◽

Unicellular Eukaryote ◽

Fundamental Parameter ◽

Secondary Endosymbiosis ◽

Spontaneous Mutation Rate

Abstract Mutations are the origin of genetic diversity, and the mutation rate is a fundamental parameter to understand all aspects of molecular evolution. The combination of mutation–accumulation experiments and high-throughput sequencing enabled the estimation of mutation rates in most model organisms, but several major eukaryotic lineages remain unexplored. Here, we report the first estimation of the spontaneous mutation rate in a model unicellular eukaryote from the Stramenopile kingdom, the diatom Phaeodactylum tricornutum (strain RCC2967). We sequenced 36 mutation accumulation lines for an average of 181 generations per line and identified 156 de novo mutations. The base substitution mutation rate per site per generation is μbs = 4.77 × 10−10 and the insertion–deletion mutation rate is μid = 1.58 × 10−11. The mutation rate varies as a function of the nucleotide context and is biased toward an excess of mutations from GC to AT, consistent with previous observations in other species. Interestingly, the mutation rates between the genomes of organelles and the nucleus differ, with a significantly higher mutation rate in the mitochondria. This confirms previous claims based on indirect estimations of the mutation rate in mitochondria of photosynthetic eukaryotes that acquired their plastid through a secondary endosymbiosis. This novel estimate enables us to infer the effective population size of P. tricornutum to be Ne∼8.72 × 106.

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HIGH MUTABILITY IN MALE HYBRIDS OF DROSOPHILA MELANOGASTER

Genetics ◽

10.1093/genetics/96.2.479 ◽

1980 ◽

Vol 96 (2) ◽

pp. 479-490 ◽

Cited By ~ 1

Author(s):

Michael J Simmons ◽

Nancy A Johnson ◽

Thomas M Fahey ◽

Sue M Nellett ◽

John D Raymond

Keyword(s):

Drosophila Melanogaster ◽

Mutation Rate ◽

Reciprocal Cross ◽

Mutation Rates ◽

Mutation Induction ◽

Hybrid Male ◽

Lethal Mutations ◽

The Cross ◽

The Relationship ◽

Reciprocal Mating

ABSTRACT The frequencies of sex-linked lethal mutations arising in hybrid male offspring from various crosses and in nonhybrid controls were determined. The hybrids were produced by crossing representative strains of the P-M system of hybrid dysgenesis in all possible combinations. Males from the cross of P males × M females had a mutation rate about 15 times higher than that of nonhybrid males from the P strain. Genetically identical males from the reciprocal cross had a mutation rate 3 to 4 times that of the nonhybrids. For crosses involving a Q strain, a significant increase in the mutation rate was detected in males produced by matings of Q males with M females. No increase was observed in genetically identical males from the reciprocal mating. Crosses between P and Q strains gave male hybrids with mutation rates not different from those of nonhybrids. Many of the lethals that occurred in hybrids from the cross of P males × M females appeared to be unstable; fewer lethals that arose in hybrids from the cross of Q males × M females were unstable. The relationship between P and Q strains is discussed with respect to a model of mutation induction in dysgenic hybrids.

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Intraspecific Variation in Microsatellite Mutation Profiles in Daphnia magna

10.1101/540773 ◽

2019 ◽

Author(s):

Eddie K. H. Ho ◽

Fenner Macrae ◽

Leigh C. Latta ◽

Maia J. Benner ◽

Cheng Sun ◽

...

Keyword(s):

Daphnia Magna ◽

Tandem Repeats ◽

Mutation Accumulation ◽

Mutation Rates ◽

Evolutionary Forces ◽

Repeat Content ◽

Long Time ◽

Order Of Magnitude ◽

Time Periods ◽

Microsatellite Mutation

AbstractMicrosatellite loci (tandem repeats of short nucleotide motifs) are highly abundant in eukaryotic genomes and are often used as genetic markers because they can exhibit variation both within and between populations. Although widely recognized for their mutability and utility, the mutation rates of microsatellites have only been empirically estimated in a few species and have rarely been compared across genotypes and populations and intraspecific differences in overall microsatellite content have rarely been explored. To investigate the accumulation of microsatellite DNA over long-and short-time periods, we quantified the abundance and genome-wide mutation rates in whole-genome sequences of 47 mutation accumulation (MA) lines and 12 non-MA lines derived from six different genotypes of the crustacean Daphnia magna collected from three populations (Finland, Germany, and Israel). Each genotype possessed a distinctive microsatellite profile and clustered according to their population of origin. During the period of mutation accumulation, we observed very high microsatellite mutation rates (a net change of −0.19 to 0.33 per copy per generation), which surpass rates reported from a closely-related congener, D. pulex, by an order of magnitude. Rates vary between microsatellite motifs and among genotypes, with those starting with high microsatellite content exhibiting greater losses and those with low microsatellite content exhibiting greater gains. Our results show that microsatellite mutation rates depend both on characteristics of the microsatellites and the genomic background. These context-dependent mutation dynamics may, in conjunction with other evolutionary forces that may differ among populations, explain the differential accumulation of repeat content in the genome over long time periods.

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Mutation rates at a new set of specific loci in the mouse

Genetics Research ◽

10.1017/s0016672300009435 ◽

1966 ◽

Vol 7 (1) ◽

pp. 12-17 ◽

Cited By ~ 59

Author(s):

Mary F. Lyon ◽

T. Morris

Keyword(s):

Drosophila Melanogaster ◽

Radiation Dose ◽

Mutation Rate ◽

Mutation Rates ◽

Specific Locus

Previous measurements of specific locus mutation rates in mice had all involved the seven loci, a, b, c, d, p, s and se. An experiment was performed with the same mouse stock (C3H × 101) and the same radiation dose (600 rad) to spermatogonia as had been used previously, but employing a new group of six loci, a, bp, fz, In, pa and pe. The observed mutation rate, 5·0 × 10−8 per locus per rad, was significantly lower than that for the original seven loci, but was three to four times higher than the corresponding mutation rate in Drosophila melanogaster.

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Mutation accumulation and the effect of copia insertions in Drosophila melanogaster

Genetics Research ◽

10.1017/s0016672303006505 ◽

2004 ◽

Vol 83 (1) ◽

pp. 7-18 ◽

Cited By ~ 47

Author(s):

DAVID HOULE ◽

SERGEY V. NUZHDIN

Keyword(s):

Drosophila Melanogaster ◽

Mutation Rate ◽

Deleterious Mutation ◽

Mutation Accumulation ◽

Inbred Lines ◽

High Rate ◽

Confidence Limits ◽

Laboratory Environment ◽

Element Number ◽

Mutational Variance

Repeated efforts to estimate the genomic deleterious mutation rate per generation (U) in Drosophila melanogaster have yielded inconsistent estimates ranging from 0·01 to nearly 1. We carried out a mutation-accumulation experiment with a cryopreserved control population in hopes of resolving some of the uncertainties raised by these estimates. Mutation accumulation (MA) was carried out by brother–sister mating of 150 sublines derived from two inbred lines. Fitness was measured under conditions chosen to mimic the ancestral laboratory environment of these genotypes. We monitored the insertions of a transposable element, copia, that proved to accumulate at the unusually high rate of 0·24 per genome per generation in one of our MA lines. Mutational variance in fitness increased at a rate consistent with previous studies, yielding a mutational coefficient of variation greater than 3%. The performance of the cryopreserved control relative to the MA lines was inconsistent, so estimates of mutation rate by the Bateman–Mukai method are suspect. Taken at face value, these data suggest a modest decline in fitness of about 0·3% per generation. The element number of copia was a significant predictor of fitness within generations; on average, insertions caused a 0·76% loss in fitness, although the confidence limits on this estimate are wide.

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Likelihood-Based Estimation of Microsatellite Mutation Rates

Genetics ◽

10.1093/genetics/164.2.781 ◽

2003 ◽

Vol 164 (2) ◽

pp. 781-787 ◽

Cited By ~ 2

Author(s):

John C Whittaker ◽

Roger M Harbord ◽

Nicola Boxall ◽

Ian Mackay ◽

Gary Dawson ◽

...

Keyword(s):

Mutation Rate ◽

Mutation Rates ◽

Parameter Estimates ◽

Step Size ◽

Exponential Relationship ◽

Length Increase ◽

Microsatellite Evolution ◽

Competing Models ◽

Allele Length ◽

Microsatellite Mutation

Abstract Microsatellites are widely used in genetic analyses, many of which require reliable estimates of microsatellite mutation rates, yet the factors determining mutation rates are uncertain. The most straightforward and conclusive method by which to study mutation is direct observation of allele transmissions in parent-child pairs, and studies of this type suggest a positive, possibly exponential, relationship between mutation rate and allele size, together with a bias toward length increase. Except for microsatellites on the Y chromosome, however, previous analyses have not made full use of available data and may have introduced bias: mutations have been identified only where child genotypes could not be generated by transmission from parents' genotypes, so that the probability that a mutation is detected depends on the distribution of allele lengths and varies with allele length. We introduce a likelihood-based approach that has two key advantages over existing methods. First, we can make formal comparisons between competing models of microsatellite evolution; second, we obtain asymptotically unbiased and efficient parameter estimates. Application to data composed of 118,866 parent-offspring transmissions of AC microsatellites supports the hypothesis that mutation rate increases exponentially with microsatellite length, with a suggestion that contractions become more likely than expansions as length increases. This would lead to a stationary distribution for allele length maintained by mutational balance. There is no evidence that contractions and expansions differ in their step size distributions.

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Mutation rate and spectrum in Caenorhabditis elegans mutation accumulation lines subjected to RNAi-induced knockdown of the mismatch repair gene msh-2

10.1101/2021.07.12.452034 ◽

2021 ◽

Author(s):

Vaishali Katju ◽

Anke Konrad ◽

Thaddeus C. Deiss ◽

Ulfar Bergthorsson

Keyword(s):

Caenorhabditis Elegans ◽

Mismatch Repair ◽

Mutation Rate ◽

Copy Number ◽

Mutation Accumulation ◽

Mutation Rates ◽

Mutational Bias ◽

C Elegans ◽

Small Indels ◽

Local Sequence

DNA mismatch repair (MMR), an evolutionarily conserved repair pathway shared by prokaryotic and eukaryotic species alike, influences molecular evolution by detecting and correcting mismatches that escape DNA polymerase proofreading, thereby protecting genetic fidelity, reducing the mutational load, and preventing lethality. Herein we conduct the first genome-wide evaluation of the alterations to the mutation rate and spectrum under impaired activity of the MutS homolog, msh-2, in Caenorhabditis elegans. We performed mutation accumulation (MA) under RNAi-induced knockdown of msh-2 for 50 generations in obligately outcrossing fog-2(lf) lines, followed by next-generation sequencing of 19 MA lines and the ancestral control. msh-2 impairment substantially increased the frequency of nuclear base substitutions (~23x) and small indels (~328x) relative to wildtype. However, we observed no increase in the mutation rates of mtDNA, and copy-number changes of single-copy genes. There was a marked increase in copy-number variation of rDNA genes under MMR impairment. In C. elegans, msh-2 repairs transitions more efficiently than transversions as well as increases the AT mutational bias relative to wildtype. The local sequence context, including sequence complexity, G+C-content, and flanking bases influenced the mutation rate. The X chromosome had a lower substitution and higher indel rate than autosomes, which can either result from sex-specific mutation rates or a nonrandom distribution of mutable sites in the genome. Comparison of MMR impairment in C. elegans to that in other species shows that the specificity of the MMR varies between taxa, and is more efficient in detecting and repairing small indels in eukaryotes relative to prokaryotes.

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Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment

Genome Biology and Evolution ◽

10.1093/gbe/evz140 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1971-1985 ◽

Cited By ~ 2

Author(s):

Marina McDew-White ◽

Xue Li ◽

Standwell C Nkhoma ◽

Shalini Nair ◽

Ian Cheeseman ◽

...

Keyword(s):

False Negative ◽

Natural Populations ◽

Point Mutations ◽

Length Change ◽

Mutation Accumulation ◽

Mutation Rates ◽

Single Infection ◽

Independent Sequence ◽

Duplicate Sequence ◽

Microsatellite Mutation

Abstract Malaria parasites have small extremely AT-rich genomes: microsatellite repeats (1–9 bp) comprise 11% of the genome and genetic variation in natural populations is dominated by repeat changes in microsatellites rather than point mutations. This experiment was designed to quantify microsatellite mutation patterns in Plasmodium falciparum. We established 31 parasite cultures derived from a single parasite cell and maintained these for 114–267 days with frequent reductions to a single cell, so parasites accumulated mutations during ∼13,207 cell divisions. We Illumina sequenced the genomes of both progenitor and end-point mutation accumulation (MA) parasite lines in duplicate to validate stringent calling parameters. Microsatellite calls were 99.89% (GATK), 99.99% (freeBayes), and 99.96% (HipSTR) concordant in duplicate sequence runs from independent sequence libraries, whereas introduction of microsatellite mutations into the reference genome revealed a low false negative calling rate (0.68%). We observed 98 microsatellite mutations. We highlight several conclusions: microsatellite mutation rates (3.12 × 10−7 to 2.16 × 10−8/cell division) are associated with both repeat number and repeat motif like other organisms studied. However, 41% of changes resulted from loss or gain of more than one repeat: this was particularly true for long repeat arrays. Unlike other eukaryotes, we found no insertions or deletions that were not associated with repeats or homology regions. Overall, microsatellite mutation rates are among the lowest recorded and comparable to those in another AT-rich protozoan (Dictyostelium). However, a single infection (>1011 parasites) will still contain over 2.16 × 103 to 3.12 × 104 independent mutations at any single microsatellite locus.

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Histocompatibility mutations in mice: chemical induction and linkage with the H-2 locus

Genetics Research ◽

10.1017/s0016672300014361 ◽

1972 ◽

Vol 19 (2) ◽

pp. 133-143 ◽

Cited By ~ 30

Author(s):

I. K. Egorov ◽

Zinaida K. Blandova

Keyword(s):

Mutation Rate ◽

Mutation Frequency ◽

Skin Grafting ◽

The Other ◽

Mutation Rates ◽

Chemical Induction ◽

Apparent Effect ◽

Genetic Complexity ◽

Different Doses ◽

Young Mice

SUMMARYYoung mice of the strains A/Y and B10.D2 were repeatedly treated with diethylsulphate (DES) in different doses (36 to 1100 mg/kg). At the age of 9 weeks they were mated to females of the strains A. CA (‘A’ group) and C57BL/10Eg (‘D’ group) respectively. 2101 progeny of these matings were tested for histocompatibility by skin grafting. The spontaneous H-mutation rates were 6·96 × 10−4 per gamete in the A group and 9·6 × 10−4 per gamete in D group. In progeny of treated males the H-mutation rates were 0 in A group and 5·79 × 10−3 per gamete in D group, showing apparent effect of paternal DES treatment on mutation frequency in the last group. Two mutations of the H-2 locus were found, which together with the other three H-2 mutations published so far yielded a mutation rate of 5·18 × 10−4 per gamete. The mutation rate of the H-2 locus is higher than the expected rate per H-locus, indicating a great genetic complexity of H-2.

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