Models of nearly neutral mutations with particular implications for nonrandom usage of synonymous codons

1987 ◽  
Vol 24 (4) ◽  
pp. 337-345 ◽  
Author(s):  
Wen-Hsiung Li
Keyword(s):  
Synonymous Codons ◽  
Nearly Neutral Mutations ◽  
Neutral Mutations

scholarly journals Experimental Estimate of the Abundance and Effects of Nearly Neutral Mutations in the RNA Virus ϕ6

Genetics ◽  
2007 ◽  
Vol 176 (1) ◽  
pp. 467-476 ◽  
Author(s):  
Christina L. Burch ◽  
Sebastien Guyader ◽  
Daniel Samarov ◽  
Haipeng Shen
Keyword(s):  
Rna Virus ◽  
Experimental Estimate ◽  
Nearly Neutral Mutations ◽  
Neutral Mutations

scholarly journals LIMITS OF ADAPTATION: THE EVOLUTION OF SELECTIVE NEUTRALITY

Genetics ◽  
1985 ◽  
Vol 111 (3) ◽  
pp. 655-674 ◽  
Author(s):  
Daniel L Hartl ◽  
Daniel E Dykhuizen ◽  
Antony M Dean
Keyword(s):  
Enzyme Activity ◽  
Natural Selection ◽  
Concave Function ◽  
Neutral Evolution ◽  
Favorable Effect ◽  
Effective Population ◽  
Population Number ◽  
Selective Neutrality ◽  
Nearly Neutral Mutations ◽  
Neutral Mutations

ABSTRACT Many enzymes in intermediary metabolism manifest saturation kinetics in which flux is a concave function of enzyme activity and often of the Michaelis-Menten form. The result is that, when natural selection favors increased enzyme activity so as to maximize flux, a point of diminishing returns will be attained in which any increase in flux results in a disproportionately small increase in fitness. Enzyme activity ultimately will reach a level at which the favorable effect of an increase in activity is of the order 1/(4Ne) or smaller, where Ne is the effective population number. At this point, many mutations that result in small changes in activity will result in negligible changes in fitness and will be selectively nearly neutral. We propose that this process is a mechanism whereby conditions for the occurrence of nearly neutral mutations and gene substitutions can be brought about by the long-continued action of natural selection. Evidence for the hypothesis derives from metabolic theory, direct studies of flux, studies of null and other types of alleles in Drosophila melanogaster and chemostat studies in Escherichia coli. Limitations and complications of the theory include changes in environment or genetic background, enzymes with sharply defined optima of activity, overdominance, pleiotropy, multifunctional enzymes and branched metabolic pathways. We conclude that the theory is a useful synthesis that unites many seemingly unrelated observations. The principal theoretical conclusion is that the conditions for the occurrence of neutral evolution can be brought about as an indirect result of the action of natural selection.

scholarly journals Genetic variability maintained in a finite population due to mutational production of neutral and nearly neutral isoalleles

1968 ◽  
Vol 11 (3) ◽  
pp. 247-270 ◽  
Author(s):  
Motoo Kimura
Keyword(s):  
Amino Acids ◽  
Finite Population ◽  
Exact Formula ◽  
Effective Size ◽  
Approximation Formula ◽  
Synonymous Mutations ◽  
Dna Base ◽  
Nearly Neutral Mutations ◽  
Image Position ◽  
Neutral Mutations

1. The average and the effective numbers of alleles maintained in a finite population due to mutational production of neutral isoalleles were studied by mathematical analysis and computer simulation.2. The exact formula was derived for the effective number (ne) of alleles maintained in a population of effective size Ne, assuming that there are K possible allelic states and mutation occurs with equal frequency in all directions. If the number of allelic states is so large that every mutation is to a new, not pre-existing, allele, we have ne = 4Neu+1 − 2Neu2, where u is the mutation rate. Thus, the approximation formula, ne = 4Neu+1, given by Kimura & Crow (1964) is valid as long as 2Neu2 ≪ 1.3. The formula for the average number of alleles (na) maintained in a population of actual size N and effective size Ne was derived by using the method of diffusion approximation. If every mutation is to a new, not pre-existing, allele, we obtainwhere M = 4Neu. The average number of alleles as a function of M and N is listed in Table 1.4. In order to check the validity of the diffusion approximations, Monte Carlo experiments were carried out using the computer IBM 7090. The experiments showed that the approximations are satisfactory for practical purposes.5. It is estimated that among the mutations produced by DNA base substitutions, synonymous mutations, that is, those which cause no alterations of amino acids, amount roughly to 0·2–0·3 in vertebrates. Incompletely synonymous mutations, that is, those which lead to substitution of chemically similar amino acids at a different position of the polypeptide chain from the active site and therefore produce almost no phenotypic effects, must be very common. Together with synonymous mutations, they might constitute at least some 40% of all mutations. These considerations suggest that neutral and nearly neutral mutations must be more common than previously considered.

Bacterial Evolution Through the Selective Loss of Beneficial Genes: Trade-Offs in Expression Involving Two Loci

Genetics ◽  
2003 ◽  
Vol 164 (4) ◽  
pp. 1271-1277
Author(s):  
Erik R Zinser ◽  
Dominique Schneider ◽  
Michel Blot ◽  
Roberto Kolter
Keyword(s):  
Regulatory Element ◽  
Direct Selection ◽  
Ecological Specialization ◽  
Positive Role ◽  
Major Mechanism ◽  
Trade Offs ◽  
Upstream Regulatory Element ◽  
Nearly Neutral Mutations ◽  
Or Gene ◽  
Neutral Mutations

AbstractThe loss of preexisting genes or gene activities during evolution is a major mechanism of ecological specialization. Evolutionary processes that can account for gene loss or inactivation have so far been restricted to one of two mechanisms: direct selection for the loss of gene activities that are disadvantageous under the conditions of selection (i.e., antagonistic pleiotropy) and selection-independent genetic drift of neutral (or nearly neutral) mutations (i.e., mutation accumulation). In this study we demonstrate with an evolved strain of Escherichia coli that a third, distinct mechanism exists by which gene activities can be lost. This selection-dependent mechanism involves the expropriation of one gene’s upstream regulatory element by a second gene via a homologous recombination event. Resulting from this genetic exchange is the activation of the second gene and a concomitant inactivation of the first gene. This gene-for-gene expression tradeoff provides a net fitness gain, even if the forfeited activity of the first gene can play a positive role in fitness under the conditions of selection.

scholarly journals Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates.

Genetics ◽  
1991 ◽  
Vol 129 (3) ◽  
pp. 957-962 ◽  
Author(s):  
J Ninio
Keyword(s):  
Steady State ◽  
Synonymous Codon ◽  
Experimental Manipulation ◽  
Mutation Rates ◽  
Wild Type ◽  
Lethal Mutations ◽  
Nearly Neutral Mutations ◽  
Neutral Mutations ◽  
Translation Errors ◽  
State Composition

Abstract A population of bacteria growing in a nonlimiting medium includes mutator bacteria and transient mutators defined as wild-type bacteria which, due to occasional transcription or translation errors, display a mutator phenotype. A semiquantitative theoretical analysis of the steady-state composition of an Escherichia coli population suggests that true strong genotypic mutators produce about 3 x 10(-3) of the single mutations arising in the population, while transient mutators produce at least 10% of the single mutations and more than 95% of the simultaneous double mutations. Numbers of mismatch repair proteins inherited by the offspring, proportions of lethal mutations and mortality rates are among the main parameters that influence the steady-state composition of the population. These results have implications for the experimental manipulation of mutation rates and the evolutionary fixation of frequent but nearly neutral mutations (e.g., synonymous codon substitutions).

scholarly journals MUTATION RATE AND DOMINANCE OF GENES AFFECTING VIABILITY IN DROSOPHILA MELANOGASTER

Genetics ◽  
1972 ◽  
Vol 72 (2) ◽  
pp. 335-355
Author(s):  
Terumi Mukai ◽  
Sadao I Chigusa ◽  
L E Mettler ◽  
James F Crow
Keyword(s):  
Drosophila Melanogaster ◽  
Mutation Rate ◽  
Genetic Variance ◽  
Genetic Load ◽  
Spontaneous Mutations ◽  
Average Effect ◽  
Lethal Mutations ◽  
Nearly Neutral Mutations ◽  
The Individual ◽  
Neutral Mutations

ABSTRACT Spontaneous mutations were allowed to accumulate in a second chromosome that was transmitted only through heterozygous males for 40 generations. At 10-generation intervals the chromosomes were assayed for homozygous effects of the accumulated mutants. From the regression of homozygous viability on the number of generations of mutant accumulation and from the increase in genetic variance between replicate chromosomes it is possible to estimate the mutation rate and average effect of the individual mutants. Lethal mutations arose at a rate of 0.0060 per chromosome per generation. The mutants having small effects on viability are estimated to arise with a frequency at least 10 times as high as lethals, more likely 20 times as high, and possibly many more times as high if there is a large class of very nearly neutral mutations.—The dominance of such mutants was measured for chromosomes extracted from a natural population. This was determined from the regression of heterozygous viability on that of the sum of the two constituent homozygotes. The average dominance for minor viability genes in an equilibrium population was estimated to be 0.21. This is lower than the value for new mutants, as expected since those with the greatest heterozygous effect are most quickly eliminated from the population. That these mutants have a disproportionately large heterozygous effect on total fitness (as well as on the viability component thereof) is shown by the low ratio of the genetic load in equilibrium homozygotes to that of new mutant homozygotes.

Genetic homologies among nocardiae and other actinomycetes

1973 ◽  
Vol 19 (8) ◽  
pp. 1007-1014 ◽  
Author(s):  
S. G. Bradley ◽  
G. H. Brownell ◽  
Josephine Clark
Keyword(s):  
Dna Hybridization ◽  
Genetic Recombination ◽  
Nucleotide Sequences ◽  
Dna Reassociation ◽  
Hybrid Molecules ◽  
Nearly Neutral Mutations ◽  
Neutral Mutations ◽  
Incubation Temperatures ◽  
Duplex Formation ◽  
Discrete Populations

The extent of association between deoxyribonucleic acid (DNA) from various actinomycetes with reference DNA samples from two strains of Nocardia erythropolis has been used as an index of relatedness. N. erythropolis, N. canicruria, and particular cultures designated as N. corallina and N. opaca constitute a genospecies, on the bases of ability to form DNA hybrid molecules and ability to participate in genetic recombination. The lack of reciprocity in the DNA reassociation assays involving selected strains of N. erythropolis indicates that the DNA from particular lineages possesses unique nucleotide sequences. The taxon Mycobacterium rhodochrous is heterogeneous and contains at least two discrete populations. The present results do not clarify the relationships of the N. erythropolis genospecies to the other nocardiae, streptomycetes, or mycobacteria. The differences in extent of hybrid DNA duplex formation at exacting and non-exacting incubation temperatures reflect the degree of matching between the compared nucleotide sequences. On this basis, actinomycete DNA samples differ from one another by nucleotide alterations dispersed throughout the genome. DNA hybridization is a sensitive assay for molecular evolution and may be able to detect neutral and nearly neutral mutations that are not recognized phenotypically.

scholarly journals Selection on Accessible Chromatin Regions in Capsella grandiflora

2021 ◽  
Author(s):  
Robert Horvath ◽  
Emily B Josephs ◽  
Edouard Pesquet ◽  
John R Stinchcombe ◽  
Stephen I Wright ◽  
...  
Keyword(s):  
Evolutionary Processes ◽  
Regulatory Regions ◽  
Noncoding Regions ◽  
Fitness Effects ◽  
Population Genomic ◽  
Intergenic Regions ◽  
Nearly Neutral Mutations ◽  
Neutral Mutations ◽  
Accessible Chromatin ◽  
New Mutations

Abstract Accurate estimates of genome-wide rates and fitness effects of new mutations are essential for an improved understanding of molecular evolutionary processes. Although eukaryotic genomes generally contain a large noncoding fraction, functional noncoding regions and fitness effects of mutations in such regions are still incompletely characterized. A promising approach to characterize functional noncoding regions relies on identifying accessible chromatin regions (ACRs) tightly associated with regulatory DNA. Here, we applied this approach to identify and estimate selection on ACRs in Capsella grandiflora, a crucifer species ideal for population genomic quantification of selection due to its favorable population demography. We describe a population-wide ACR distribution based on ATAC-seq data for leaf samples of 16 individuals from a natural population. We use population genomic methods to estimate fitness effects and proportions of positively selected fixations (α) in ACRs and find that intergenic ACRs harbor a considerable fraction of weakly deleterious new mutations, as well as a significantly higher proportion of strongly deleterious mutations than comparable inaccessible intergenic regions. ACRs are enriched for expression quantitative trait loci (eQTL) and depleted of transposable element insertions, as expected if intergenic ACRs are under selection because they harbor regulatory regions. By integrating empirical identification of intergenic ACRs with analyses of eQTL and population genomic analyses of selection, we demonstrate that intergenic regulatory regions are an important source of nearly neutral mutations. These results improve our understanding of selection on noncoding regions and the role of nearly neutral mutations for evolutionary processes in outcrossing Brassicaceae species.

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