Effect of demographic population factors and individual biological parameters on the rate of neutral molecular evolution

The dependence of the rate of neutral molecular evolution on biological parameters and demographic population factors was studied based on actual genetic information as an example and using the individual-oriented model of population dynamics. The first part of the study deals with tracing the neutral evolution occurring in the model concurrently with adaptive speciation. The second part concerns the effect of individual biological parameters and demographic population factors of members of the order Testudines (turtles) on the relative evolution rate of the mitochondrial CytB gene. Demographic population factors and individual biological parameters are shown to affect the rate of molecular evolution.     

The effect of population structure on the rate of evolution

Ecological factors exert a range of effects on the dynamics of the evolutionary process. A particularly marked effect comes from population structure, which can affect the probability that new mutations reach fixation. Our interest is in population structures, such as those depicted by ‘star graphs’, that amplify the effects of selection by further increasing the fixation probability of advantageous mutants and decreasing the fixation probability of disadvantageous mutants. The fact that star graphs increase the fixation probability of beneficial mutations has lead to the conclusion that evolution proceeds more rapidly in star-structured populations, compared with mixed (unstructured) populations. Here, we show that the effects of population structure on the rate of evolution are more complex and subtle than previously recognized and draw attention to the importance of fixation time. By comparing population structures that amplify selection with other population structures, both analytically and numerically, we show that evolution can slow down substantially even in populations where selection is amplified.     

Rainbow trout: a population simulation based on individual responses to varying environmental and demographic parameters

Synopsis An age-structured simulation model of the growth and population dynamics of a migratory rainbow trout population is presented. The model includes all principal life-history intervals and incorporates the food density-temperature relationships of salmonid growth efficiency proposed by Brett et al. (1969) and Shelbourn et al. (1973). Population size, mean weight, and biomass are adjusted and output monthly over time in age, sex, and location categories; a simulation run may continue for as long as 100 years. A variety of environmental and and biological parameters are utilized in the simulation which can be altered as a user option. Simulation results compare favorably with field data. Sensitivity analyses illustrate the importance of age-sex specific maturation ratios, age-class strength fluctuations, and natural mortality rates in determining population size.     

The nearly neutral and selection theories of molecular evolution under the fisher geometrical framework: substitution rate, population size, and complexity

The general theories of molecular evolution depend on relatively arbitrary assumptions about the relative distribution and rate of advantageous, deleterious, neutral, and nearly neutral mutations. The Fisher geometrical model (FGM) has been used to make distributions of mutations biologically interpretable. We explored an FGM-based molecular model to represent molecular evolutionary processes typically studied by nearly neutral and selection models, but in which distributions and relative rates of mutations with different selection coefficients are a consequence of biologically interpretable parameters, such as the average size of the phenotypic effect of mutations and the number of traits (complexity) of organisms. A variant of the FGM-based model that we called the static regime (SR) represents evolution as a nearly neutral process in which substitution rates are determined by a dynamic substitution process in which the population's phenotype remains around a suboptimum equilibrium fitness produced by a balance between slightly deleterious and slightly advantageous compensatory substitutions. As in previous nearly neutral models, the SR predicts a negative relationship between molecular evolutionary rate and population size; however, SR does not have the unrealistic properties of previous nearly neutral models such as the narrow window of selection strengths in which they work. In addition, the SR suggests that compensatory mutations cannot explain the high rate of fixations driven by positive selection currently found in DNA sequences, contrary to what has been previously suggested. We also developed a generalization of SR in which the optimum phenotype can change stochastically due to environmental or physiological shifts, which we called the variable regime (VR). VR models evolution as an interplay between adaptive processes and nearly neutral steady-state processes. When strong environmental fluctuations are incorporated, the process becomes a selection model in which evolutionary rate does not depend on population size, but is critically dependent on the complexity of organisms and mutation size. For SR as well as VR we found that key parameters of molecular evolution are linked by biological factors, and we showed that they cannot be fixed independently by arbitrary criteria, as has usually been assumed in previous molecular evolutionary models.     

The effect of population bottlenecks on mutation rate evolution in asexual populations

In the absence of recombination, a mutator allele can spread through a population by hitchhiking with beneficial mutations that appear in its genetic background. Theoretical studies over the past decade have shown that the survival and fixation probability of beneficial mutations can be severely reduced by population size bottlenecks. Here, we use computational modelling and evolution experiments with the yeast S. cerevisiae to examine whether population bottlenecks can affect mutator dynamics in adapting asexual populations. In simulation, we show that population bottlenecks can inhibit mutator hitchhiking with beneficial mutations and are most effective at lower beneficial mutation supply rates. We then subjected experimental populations of yeast propagated at the same effective population size to three different bottleneck regimes and observed that the speed of mutator hitchhiking was significantly slower at smaller bottlenecks, consistent with our theoretical expectations. Our results, thus, suggest that bottlenecks can be an important factor in mutation rate evolution and can in certain circumstances act to stabilize or, at least, delay the progressive elevation of mutation rates in asexual populations. Additionally, our findings provide the first experimental support for the theoretically postulated effect of population bottlenecks on beneficial mutations and demonstrate the usefulness of studying mutator frequency dynamics for understanding the underlying dynamics of fitness‐affecting mutations.     

Influence of spatial and temporal heterogeneities on the estimation of demographic parameters in a continuous population using individual microsatellite data

Drift and migration disequilibrium are very common in animal and plant populations. Yet their impact on methods of estimation of demographic parameters was rarely evaluated especially in complex realistic population models. The effect of such disequilibria on the estimation of demographic parameters depends on the population model, the statistics, and the genetic markers used. Here we considered the estimation of the product Dsigma2 from individual microsatellite data, where D is the density of adults and sigma2 the average squared axial parent-offspring distance in a continuous population evolving under isolation by distance. A coalescence-based simulation algorithm was used to study the effect on Dsigma2 estimation of temporal and spatial fluctuations of demographic parameters. Estimation of present-time Dsigma2 values was found to be robust to temporal changes in dispersal, to density reduction, and to spatial expansions with constant density, even for relatively recent changes (i.e., a few tens of generations ago). By contrast, density increase in the recent past gave Dsigma2 estimations biased largely toward past demographic parameters values. The method was also robust to spatial heterogeneity in density and estimated local demographic parameters when the density is homogenous around the sampling area (e.g., on a surface that equals four times the sampling area). Hence, in the limit of the situations studied in this article, and with the exception of the case of density increase, temporal and spatial fluctuations of demographic parameters appear to have a limited influence on the estimation of local and present-time demographic parameters with the method studied.     

Estimating the rate of evolution of the rate of molecular evolution

A simple model for the evolution of the rate of molecular evolution is presented. With a Bayesian approach, this model can serve as the basis for estimating dates of important evolutionary events even in the absence of the assumption of constant rates among evolutionary lineages. The method can be used in conjunction with any of the widely used models for nucleotide substitution or amino acid replacement. It is illustrated by analyzing a data set of rbcL protein sequences.      

The role of compensatory neutral mutations in molecular evolution

A pair of mutations at different loci (or sites) which are singly deleterious but restore normal fitness in combination may be called compensatory neutral mutations. Population dynamics concerning evolutionary substitutions of such mutants was developed by making use of the diffusion equation method. Based on this theory and, also, by the help of Monte Carlo simulation experiments, a remarkable phenomenon was disclosed that the double mutants can easily become fixed in the population by random drift under continued mutation pressure if the loci arc tightly linked, even when the single mutants are definitely deleterious. More specifically, I consider two loci with allelesA andA’ in the first locus, and allelesB andB’in the second locus, and assign relative fitnesses 1, 1-s’, 1-s’ and 1 respectively to the four gene combinationsAB, A’B, AB’ andA’B’, wheres’ is the selection coefficient against the single mutants (s’ > 0). Letv be the mutation rate per locus per generation and assume that mutation occurs irreversibly fromA toA’ at the first locus, and fromB toB’ at the second locus, whereA andB are wild type genes, andA’ andB’ are their mutant alleles. In a diploid population of effective size N _e (or a haploid population of 2N _e breeding individuals), it was shown that the average time (T) until joint fixation of the double mutant (A’B’) starting from the state in which the population consists exclusively of the wild type genes (AB) is not excessively long even for large 4N _e s’ values. In fact, assuming2N _e v = 1 we have -T = 54Ne for 4Nes’ = 400, and -T = 128Ne for 4N _e s’ = 1000. These values are not unrealistically long as compared with -T~ 5N _e obtained for 4N _e s’ = 0. The approximate analytical treatment has also been extended to estimate the effect of low rate crossing over in retarding fixation. The bearing of these findings on molecular evolution is discussed with special reference to coupled substitutions at interacting amino acid (or nucleotide) sites within a folded protein (orrna) molecule. It is concluded that compensatory neutral mutants may play an important role in molecular evolution.     

The effect of recombination on the neutral evolution of genetic robustness

Conventional population genetics considers the evolution of a limited number of genotypes corresponding to phenotypes with different fitness. As model phenotypes, in particular RNA secondary structure, have become computationally tractable, however, it has become apparent that the context dependent effect of mutations and the many-to-one nature inherent in these genotype-phenotype maps can have fundamental evolutionary consequences. It has previously been demonstrated that populations of genotypes evolving on the neutral networks corresponding to all genotypes with the same secondary structure only through neutral mutations can evolve mutational robustness [E. van Nimwegen, J.P. Crutchfield, M. Huynen, Neutral evolution of mutational robustness, Proc. Natl. Acad. Sci. USA 96(17), 9716-9720 (1999)], by concentrating the population on regions of high neutrality. Introducing recombination we demonstrate, through numerically calculating the stationary distribution of an infinite population on ensembles of random neutral networks that mutational robustness is significantly enhanced and further that the magnitude of this enhancement is sensitive to details of the neutral network topology. Through the simulation of finite populations of genotypes evolving on random neutral networks and a scaled down microRNA neutral network, we show that even in finite populations recombination will still act to focus the population on regions of locally high neutrality.     

The influence of Nickel on population dynamics and on some demographic parameters of Daphnia magna

Daphnia magna was cultured with two different techniques at sublethal nickel concentrations from 0 up to 200 µg Ni l^-1. The results of the experiments run with cohorts of single individuals in static cultures were compared with the results obtained with populations held in flow through cultures. The most sensitive demographic parameters in cohorts were life span, the total number of progeny and the achievable maximum body length. The investigated nickel concentrations lowered the mean animal density in populations. Size class distribution was affected and the oscillation of the percentage of ovigorous adults increased with increasing nickel concentrations. In 200 µg Ni l^-1 one population extincted. Individuals in static cultures exposed to the same nickel concentration produced at least two neonates. Both employed techniques are discussed.     

The neutral theory of molecular evolution and the world view of the neutralists

The main tenet of the neutral theory is that the great majority of evolutionary changes at the molecular level are caused not by Darwinian selection but by random fixation of selectively neutral (or very nearly neutral) alleles through random sampling drift under continued mutation pressure. The theory also asserts that the majority of protein and DNA polymorphisms are selectively neutral, and that they are maintained in the species by mutational input balanced by random extinction rather than by "balancing selection." The neutral theory is based on simple assumptions. This enabled us to develop mathematical theories (using the diffusion equation method) that can treat these phenomena in quantitative terms and that permit theory to be tested against actual observations. Although the neutral theory has been severely criticized by the neo-Darwinian establishment, supporting evidence has accumulated over the last 20 years. In particular, the recent burst of DNA sequence data helped to strengthen the theory a great deal. I believe that the neutral theory triggered reexamination of the traditional "synthetic theory of evolution." In this paper, I review the present status of the neutral theory, including discussions of such topics as "molecular evolutionary clock," very high evolutionary rates observed in RNA viruses, a deviant coding system found in Mycoplasm together with the concept of mutation-driven neutral evolution, and the origin of life. I also present a worldview based on the conception of what I call "survival of the luckiest."     

Sociality and the rate of molecular evolution

The molecular clock does not tick at a uniform rate in all taxa but may be influenced by species characteristics. Eusocial species (those with reproductive division of labor) have been predicted to have faster rates of molecular evolution than their nonsocial relatives because of greatly reduced effective population size; if most individuals in a population are nonreproductive and only one or few queens produce all the offspring, then eusocial animals could have much lower effective population sizes than their solitary relatives, which should increase the rate of substitution of "nearly neutral" mutations. An earlier study reported faster rates in eusocial honeybees and vespid wasps but failed to correct for phylogenetic nonindependence or to distinguish between potential causes of rate variation. Because sociality has evolved independently in many different lineages, it is possible to conduct a more wide-ranging study to test the generality of the relationship. We have conducted a comparative analysis of 25 phylogenetically independent pairs of social lineages and their nonsocial relatives, including bees, wasps, ants, termites, shrimps, and mole rats, using a range of available DNA sequences (mitochondrial and nuclear DNA coding for proteins and RNAs, and nontranslated sequences). By including a wide range of social taxa, we were able to test whether there is a general influence of sociality on rates of molecular evolution and to test specific predictions of the hypothesis: (1) that social species have faster rates because they have reduced effective population sizes; (2) that mitochondrial genes would show a greater effect of sociality than nuclear genes; and (3) that rates of molecular evolution should be correlated with the degree of sociality. We find no consistent pattern in rates of molecular evolution between social and nonsocial lineages and no evidence that mitochondrial genes show faster rates in social taxa. However, we show that the most highly eusocial Hymenoptera do have faster rates than their nonsocial relatives. We also find that social parasites (that utilize the workers from related species to produce their own offspring) have faster rates than their social relatives, which is consistent with an effect of lower effective population size on rate of molecular evolution. Our results illustrate the importance of allowing for phylogenetic nonindependence when conducting investigations of determinants of variation in rate of molecular evolution.     

On the rate of molecular evolution

Summary There are at least two outstanding features that characterize the rate of evolution at the molecular level as compared with that at the phenotypic level. They are; (1) remarkable uniformity for each molecule, and (2) very high overall rate when extrapolated to the whole DNA content.The population dynamics for the rate of mutant substitution was developed, and it was shown that if mutant substitutions in the population are carried out mainly by natural selection, the rate of substitution is given byk = 4 N _e s ₁ v, whereN _e is the effective population number,s ₁ is the selective advantage of the mutants, andv is the mutation rate per gamete for such advantageous mutants (assuming that 4N _e s ₁ 1). On the other hand, if the substitutions are mainly carried out by random fixation of selectively neutral or nearly neutral mutants, we havek = v, wherev is the mutation rate per gamete for such mutants.Reasons were presented for the view that evolutionary change of amino acids in proteins has been mainly caused by random fixation of neutral mutants rather than by natural selection.It was concluded that if this view is correct, we should expect that genes of living fossils have undergone almost as many DNA base replacements as the corresponding genes of more rapidly evolving species.Contribution No. 789 from the National Institute of Genetics, Mishima, Shizuokaken 411 Japan. Aided in part by a grant-in-aid from the Ministry of Education, Japan.     

Genetic demographic parameters of the marriage structure of the Yevpatoria population

Records on marriages contracted in the city of Yevpatoria, Ukraine in 1960/1961, 1985, 1993, and 1994/1995 were used to determine some parameters of the city population structure. The coefficients of correlation with respect to the age of marriage in reproductive-age couples contracting marriages in these years were 0.77, 0.81, and 0.80, respectively. Women that contracted marriages at reproductively unfavorable ages (under 20 and over 30 years) in the respective years constituted 28.3, 40.6, and 45.4% of the total sample. The proportions of interethnic marriages in these years were 39.4, 43.9, and 46.6%. The proportion of Slavs decreased from 94 to 91% during 35 years, but the proportion of Ukrainians increased from 23.1 to 26.5%. The proportion of other ethnic groups (Tatars, Armenians, Karaites, Poles, Germans, etc.) increased from 3 to 8.6%. The marriage contingency with respect to ethnicity (K = 0.26 in 1960/1961, K = 0.22 in 1985, and K = 0.28 in 1994/1995) was higher than with respect to education (K = 0.18 in 1985 and K = 0.23 in 1993) or occupation (K = 0.18 in 1960/1961, K = 0.17 in 1985, and K = 0.23 in 1994/1995). The marriage assortativeness with respect to ethnicity was the highest in ethnic minorities (A' = 55.1%); that with respect to education, in persons who had higher or primary education (A' = 40.1% and A'= 78.0%, respectively); and that with respect to occupation, in students, military personnel, and production workers (60.6, 58.7, and 30.9%).     

Genetic demographic parameters of the marriage structure of the Yevpatoria population

Records on marriages contracted in the city of Yevpatoria, Ukraine in 1960/1961, 1985, 1993, and 1994/1995 were used to determine some parameters of the city population structure. The coefficients of correlation with respect to the age of marriage in reproductive-age couples contracting marriages in these years were 0.77, 0.81, and 0.80, respectively. Women that contracted marriages at reproductively unfavorable ages (under 20 and over 30 years) in the respective years constituted 28.3, 40.6, and 45.4% of the total sample. The proportions of interethnic marriages in these years were 39.4, 43.9, and 46.6%. The proportion of Slavs decreased from 94 to 91% during 35 years, but the proportion of Ukrainians increased from 23.1 to 26.5%. The proportion of other ethnic groups (Tatars, Armenians, Karaites, Poles, Germans, etc.) increased from 3 to 8.6%. The marriage contingency with respect to ethnicity (K = 0.26 in 1960/1961, K = 0.22 in 1985, and K = 0.28 in 1994/1995) was higher than with respect to education (K = 0.18 in 1985 and K = 0.23 in 1993) or occupation (K = 0.18 in 1960/1961, K = 0.17 in 1985, and K = 0.23 in 1993). The marriage assortativeness with respect to ethnicity was the highest in ethnic minorities (A′ = 55.1%); that with respect to education, in persons who had higher or primary education (A′ = 40.1% and A′ = 78.0%, respectively); and that with respect to occupation, in students, military personnel, and production workers (60.6, 58.7, and 30.9%).     

A generation‐time effect on the rate of molecular evolution in bacteria

Molecular evolutionary rate varies significantly among species and a strict global molecular clock has been rejected across the tree of life. Generation time is one primary life‐history trait that influences the molecular evolutionary rate. Theory predicts that organisms with shorter generation times evolve faster because of the accumulation of more DNA replication errors per unit time. Although the generation‐time effect has been demonstrated consistently in plants and animals, the evidence of its existence in bacteria is lacking. The bacterial phylum Firmicutes offers an excellent system for testing generation‐time effect because some of its members can enter a dormant, nonreproductive endospore state in response to harsh environmental conditions. It follows that spore‐forming bacteria would—with their longer generation times—evolve more slowly than their nonspore‐forming relatives. It is therefore surprising that a previous study found no generation‐time effect in Firmicutes. Using a phylogenetic comparative approach and leveraging on a large number of Firmicutes genomes, we found sporulation significantly reduces the genome‐wide spontaneous DNA mutation rate and protein evolutionary rate. Contrary to the previous study, our results provide strong evidence that the evolutionary rates of bacteria, like those of plants and animals, are influenced by generation time.