Studies Of Mutation Rates Research Articles

A new era of mutation rate analyses: Concepts and methods.

The mutation rate is a pivotal biological characteristic, intricately governed by natural selection and historically garnering considerable attention. Recent advances in high-throughput sequencing and analytical methodologies have profoundly transformed our understanding in this domain, ushering in an unprecedented era of mutation rate research. This paper aims to provide a comprehensive overview of the key concepts and methodologies frequently employed in the study of mutation rates. It examines various types of mutations, explores the evolutionary dynamics and associated theories, and synthesizes both classical and contemporary hypotheses. Furthermore, this review comprehensively explores recent advances in understanding germline and somatic mutations in animals and offers an overview of experimental methodologies, mutational patterns, molecular mechanisms, and driving forces influencing variations in mutation rates across species and tissues. Finally, it proposes several potential research directions and pressing questions for future investigations.

Evolution of the germline mutation rate across vertebrates

The germline mutation rate determines the pace of genome evolution and is an evolving parameter itself1. However, little is known about what determines its evolution, as most studies of mutation rates have focused on single species with different methodologies2. Here we quantify germline mutation rates across vertebrates by sequencing and comparing the high-coverage genomes of 151 parent–offspring trios from 68 species of mammals, fishes, birds and reptiles. We show that the per-generation mutation rate varies among species by a factor of 40, with mutation rates being higher for males than for females in mammals and birds, but not in reptiles and fishes. The generation time, age at maturity and species-level fecundity are the key life-history traits affecting this variation among species. Furthermore, species with higher long-term effective population sizes tend to have lower mutation rates per generation, providing support for the drift barrier hypothesis3. The exceptionally high yearly mutation rates of domesticated animals, which have been continually selected on fecundity traits including shorter generation times, further support the importance of generation time in the evolution of mutation rates. Overall, our comparative analysis of pedigree-based mutation rates provides ecological insights on the mutation rate evolution in vertebrates.

An ordered crossover based approach to designing labeling diversity mappers

AbstractGenetic algorithms (GAs) are population‐based search optimization techniques that mimic the process of evolution and natural selection. GAs are an effective way of finding feasible solutions to complex problems. Recently, GAs were applied to the labeling diversity (LD) problem that produced local optimal mappers for M‐QAM, M‐PSK, and M‐APSK constellations. However, the GA did not implement biological processes during the mating process; hence it could not be classified as a GA, but rather a genetic‐inspired algorithm (GIA). In this article, we investigate the application of six distinct crossover techniques to further improve the GIAs ability to produce more closer‐to‐optimal mapper designs. By using biological crossover techniques, offspring produced acquires genetic diversity from parent chromosomes. Single parent crossover techniques do not produce diversified offspring, thus diversity being acquired only by mutation. The Davis ordered crossover (OX1) was chosen as a suitable technique to be applied to the proposed GA. The proposed GA was tested on 16QAM, 16PSK, 16APSK, and three 16APSK constellations that do not exhibit diagonal symmetry. In the case of the 16QAM and 16PSK constellations, the proposed GA matched but did not improve upon existing mapper designs. In the case of the 16APSK and 11+5APSK constellations, the proposed GA produced mapper designs exhibited diversity gains of dB over the existing GIA mapper designs at the BER of. The asymmetric 16APSK and single symmetry 16APSK constellations exhibited diversity gains ofand dB over existing GIA mapper designs at the BER ofand. More significantly, the proposed GA achieved a significant improvement in time complexity. However, the proposed GA was shown to have higher computational complexity ofover the GIA with a complexity of. Mutation rate studies have shown that for single‐parent crossover techniques, higher mutation rates are needed, thus making the process is purely random. In the case of the two‐parent crossover technique, randomness is reduced and genetic diversity is increased, hence lower mutation rates were required due to a more guided search.

Lessons from Reverse Translation.

Lessons from Reverse Translation.

Genome dynamics during experimental evolution

Evolutionary changes in organismal traits may occur either gradually or suddenly. However, until recently, there has been little direct information about how phenotypic changes are related to the rate and the nature of the underlying genotypic changes. Technological advances that facilitate whole-genome and whole-population sequencing, coupled with experiments that 'watch' evolution in action, have brought new precision to and insights into studies of mutation rates and genome evolution. In this Review, we discuss the evolutionary forces and ecological processes that govern genome dynamics in various laboratory systems in the context of relevant population genetic theory, and we relate these findings to evolution in natural populations.

Germline Mutations of Tetranucleotide DNA Repeats in Families with Normal Children and Reproductive Pathology

We have previously reported a high rate of tetranucleotide DNA repeat mutations, including mutations of both germline and somatic origin, in spontaneous human abortuses. To analyze in more detail mutational microsatellite (MS) variability in meiosis and its possible association with disturbed embryonic development, we have conducted a comparative study of mutation rates of a complex of 15 autosomal tetranucleotide MSs in 55 families with healthy children and in 103 families that have had spontaneous abortuses with normal karyotypes. In the families with miscarriage, the gametic MS mutation rate was higher than in the families with normal reproductive function (4.36 x 10(-3) versus 2.32 x 10(-3) per locus per gamete per generation), but this difference was statistically nonsignificant (P = 0.25). No association of MS mutations with familiar miscarriage was found. Mutations at the MS loci studied were recorded almost 3 times as often in spermatogenesis as in oogenesis, which is likely to result from a greater number of DNA replication cycles in male germline cell precursors than in female ones. Mutations increasing and reducing the MS sequence length appeared at virtually the same rate. Changes in MS DNA sequence length per one repeated element, i.e., single-step mutations (93% of cases) exceeded all other events of allele length change. The highest number of mutations (81.2%) was found in longer alleles. This distribution of mutations by size, direction, and parental origin corresponds to the multistep mutation model of their emergence via mechanism of DNA strand slippage during replication.

A study of mutation rates and the characterisation of intermediate, null and duplicated alleles for 13 Y chromosome STRs

Previously reported Y chromosome STR haplotype databases for three UK population groups, plus additionally analysed samples, have been scrutinised for the presence of non-standard (intermediate, null and duplicated) alleles. These alleles have been characterised by sequencing, some showing changes in the repeat structure, and the frequencies reported. Mutation rates for each of the 13 STRs have been calculated when analysis of father–son pairs has been possible. An example illustrating the use of non-standard alleles in a large family tree is outlined.

Polyoxin Resistance of Reddish Brown Laboratory Mutants of Cochliobolus heterostrophus

Six reddish brown polyxin-resistant mutants of Cochliobolus heterostrophus were isolated after ethyl methanesul-phonate and N-nitroquinoline oxide mutageneses followed by selection on polyoxin. All the mutants were highly resistant to polyoxin (MIC > 1600 μg/ml). When mutants were crossed with the wild-type strain, all crosses had a 1 : 1 ratio of mutant (reddish brown pigmentation and polyoxin resistance) : wild type (non-reddish brown pigmentation and polyoxin sensitivity), indicating that the phenotypes in these strains were due to alteration at a single gene locus in each strain. Allelism tests revealed the existence of two loci, Pol2 and Pol5. The results of the crossing and mutation-rate studies suggest that the each gene was pleiotropic for the reddish brown color and polyoxin resistance.

Differing activities of quinolones against ciprofloxacin-susceptible and ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus

The in vitro activities of nine quinolones (seven fluoroquinolones, nalidixic acid, and acrosoxacin) against methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of the glycopeptides teicoplanin and vancomycin. MICs against 160 strains of ciprofloxacin-susceptible (MIC, less than 2.0 micrograms/ml) MRSA and 40 strains of ciprofloxacin-resistant (MIC, greater than or equal to 2.0 micrograms/ml) MRSA were determined. The following MICs for 50% of the strains tested (in micrograms per milliliter) were obtained for ciprofloxacin-susceptible and -resistant strains, respectively: tosufloxacin, 0.06 and 2.0; ofloxacin, 0.25 and 16; ciprofloxacin, 0.5 and 16; pefloxacin, 0.5 and 32; acrosoxacin, 1.0 and greater than 256; enoxacin, 1.0 and 64; fleroxacin, 1.0 and 32; norfloxacin, 2.0 and 64; nalidixic acid, 64 and 512; teicoplanin, 1.0 and 1.0; vancomycin, 2.0 and 2.0. In mutation rate studies using a range of antibiotic concentrations to reflect those achievable in vivo, resistant mutants grew only on plates containing nalidixic acid (rate of mutation to resistance, 10(-7) to 10(-8) and on plates containing low concentrations of ciprofloxacin, enoxacin, and norfloxacin (rate of mutation to resistance, 10(-8) to 10(-9). In time-kill studies, 99.9% killing was found within 8 h for all of the quinolones tested (norfloxacin and nalidixic acid were not tested). Teicoplanin and vancomycin were less rapidly bactericidal. For the clinical isolates of ciprofloxacin-resistant MRSA, different levels and patterns of quinolone resistance were found. Generally, cross-resistance among the fluoroquinolones was complete; however, incomplete cross-resistance did occur with the nonfluorinated quinolone acrosoxacin.

Clones of Chinese hamster cells cultivated in vitro not permanently resistant to azaguanine

The frequency of clones not permanently resistant to azaguanine (AG) was measured in Chinese hamster ovary cells (CHO) grown in vitro by plating them in 7.5 μg/ml AG and isolating a number of clones in the course of 5 experiments. Such isolated clones were propagated to a point at which their resistance to both AG and the reverse selective medium, HAT, could be determined. Out of a total of 13 clones isolated, 4 of these could not be distinguished from the parent CHO line, either on the basis of their growth in a gradient of AG concentrations or the reverse selective HAT medium or on the basis of their mutation frequency to resistance to 30 μg/ml AG. All four of the apparent phenocopies were isolated from plates in which although lower numbers of cells were seeded, a higher frequency of clones able to grow in AG was yielded. This suggests that the higher “mutation” frequencies obtained at lower cell densities are due to the appearance of phenocopies which occur only under these conditions. It is concluded that under low plating density conditions, the lower levels of AG (7.5 μg/ml) are not satisfactory for mutagenesis and mutation rate studies.

A COMPARATIVE STUDY OF MUTATION RATES IN TWO ECOLOGICALLY DIVERSE SPECIES OF DROSOPHILA

A COMPARATIVE STUDY OF MUTATION RATES IN TWO ECOLOGICALLY DIVERSE SPECIES OF DROSOPHILA