scholarly journals Divergence Times in Caenorhabditis and Drosophila Inferred from Direct Estimates of the Neutral Mutation Rate

2008 ◽  
Vol 25 (4) ◽  
pp. 778-786 ◽  
Author(s):  
A. D. Cutter
Keyword(s):  
Mutation Rate ◽  
Divergence Times ◽  
Neutral Mutation ◽  
Neutral Mutation Rate

scholarly journals Molecular population genetics of an electrophoretically monomorphic protein in the alcohol dehydrogenase region of Drosophila pseudoobscura.

Genetics ◽  
1992 ◽  
Vol 132 (1) ◽  
pp. 163-178
Author(s):  
S W Schaeffer ◽  
E L Miller
Keyword(s):  
Amino Acid ◽  
Alcohol Dehydrogenase ◽  
Mutation Rate ◽  
Statistical Tests ◽  
Drosophila Pseudoobscura ◽  
Neutral Model ◽  
Nucleotide Sequence Data ◽  
Neutral Mutation ◽  
Synonymous Sites ◽  
Neutral Mutation Rate

Abstract Nucleotide sequence data from the alcohol dehydrogenase (Adh) region of 18 isochromosomal strains of Drosophila pseudoobscura were used to determine whether the lack of amino acid polymorphism in ADH results from a low neutral mutation rate or a recent directional selection event. We estimated the neutral mutation parameter, 4Nmu, in synonymous sites for 17 subregions of Adh. The nucleotide diversity data were tested for departures from an equilibrium neutral model with two statistical tests. The Tajima test and the Hudson, Kreitman and Aguade test each failed to reject a neutral model. These results suggest that the ADH enzyme of D. pseudoobscura lacks amino acid polymorphisms because the neutral mutation rate of nonsynonymous sites is low. The neutral mutation parameter for synonymous sites is heterogeneous between domains of the Adh region. These data indicate that selective constrains on synonymous sites can vary between functional domains.

scholarly journals Estimation of the Amount of DNA Polymorphism When the Neutral Mutation Rate Varies Among Sites

Genetics ◽  
1997 ◽  
Vol 147 (4) ◽  
pp. 1959-1964 ◽  
Author(s):  
Kazuharu Misawa ◽  
Fumio Tajima
Keyword(s):  
Computer Simulations ◽  
Mutation Rate ◽  
Dna Polymorphism ◽  
Effective Population ◽  
Site Model ◽  
New Methods ◽  
Neutral Mutation ◽  
Minimum Number ◽  
New Statistics ◽  
Neutral Mutation Rate

Abstract Knowing the amount of DNA polymorphism is essential to understand the mechanism of maintaining DNA polymorphism in a natural population. The amount of DNA polymorphism can be measured by the average number of nucleotide differences per site (π), the proportion of segregating (polymorphic) site (s) and the minimum number of mutations per site (s*). Since the latter two quantities depend on the sample size, θ is often used as a measure of the amount of DNA polymorphism, where θ = 4Nμ, N is the effective population size and μ is the neutral mutation rate per site per generation. It is known that θ estimated from π, s and s* under the infinite site model can be biased when the mutation rate varies among sites. We have therefore developed new methods for estimating θ under the finite site model. Using computer simulations, it has been shown that the new methods give almost unbiased estimates even when the mutation rate varies among sites substantially. Furthermore, we have also developed new statistics for testing neutrality by modifying Tajima's D statistic. Computer simulations suggest that the new test statistics can be used even when the mutation rate varies among sites.

scholarly journals The Amount of DNA Polymorphism Maintained in a Finite Population When the Neutral Mutation Rate Varies Among Sites

Genetics ◽  
1996 ◽  
Vol 143 (3) ◽  
pp. 1457-1465 ◽  
Author(s):  
Fumio Tajima
Keyword(s):  
Mutation Rate ◽  
Finite Population ◽  
Rate Variation ◽  
Effective Population ◽  
Site Model ◽  
New Methods ◽  
Infinite Site Model ◽  
Minimum Number ◽  
Input Model ◽  
Neutral Mutation Rate

Abstract The expectations of the average number of nucleotide differences per site (π), the proportion of segregating site (s), the minimum number of mutations per site (s*) and some other quantities were derived under the finite site models with and without rate variation among sites, where the finite site models include Jukes and Cantor's model, the equal-input model and Kimura's model. As a model of rate variation, the gamma distribution was used. The results indicate that if distribution parameter α is small, the effect of rate variation on these quantities are substantial, so that the estimates of θ based on the infinite site model are substantially underestimated, where θ = 4Nv, N is the effective population size and vis the mutation rate per site per generation. New methods for estimating θ are also presented, which are based on the finite site models with and without rate variation. Using these methods, underestimation can be corrected.

scholarly journals The germline mutational process in rhesus macaque and its implications for phylogenetic dating

2020 ◽  
Author(s):  
Lucie A. Bergeron ◽  
Søren Besenbacher ◽  
Jaco Bakker ◽  
Jiao Zheng ◽  
Panyi Li ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Mutation Rate ◽  
De Novo ◽  
Rhesus Macaques ◽  
Average Rate ◽  
Paternal Age ◽  
Divergence Times ◽  
Sequencing Coverage ◽  
Parental Bias ◽  
Mutational Process

AbstractUnderstanding the rate and pattern of germline mutations is of fundamental importance for understanding evolutionary processes. Here we analyzed 19 parent-offspring trios of rhesus macaques (Macaca mulatta) at high sequencing coverage of ca. 76X per individual, and estimated an average rate of 0.77 × 10−8de novo mutations per site per generation (95 % CI: 0.69 × 10−8 - 0.85 × 10−8). By phasing 50 % of the mutations to parental origins, we found that the mutation rate is positively correlated with the paternal age. The paternal lineage contributed an average of 81 % of the de novo mutations, with a trend of an increasing male contribution for older fathers. About 3.5 % of de novo mutations were shared between siblings, with no parental bias, suggesting that they arose from early development (postzygotic) stages. Finally, the divergence times between closely related primates calculated based on the yearly mutation rate of rhesus macaque generally reconcile with divergence estimated with molecular clock methods, except for the Cercopithecidae/Hominoidea molecular divergence dated at 52 Mya using our new estimate of the yearly mutation rate.

scholarly journals Population size and protein variation in man

1972 ◽  
Vol 19 (1) ◽  
pp. 73-89 ◽  
Author(s):  
John Haigh ◽  
John Maynard Smith
Keyword(s):  
Population Size ◽  
Effective Population ◽  
Human Species ◽  
Neutral Mutation ◽  
Mutation Theory ◽  
Neutral Mutation Theory ◽  
Pattern Of Variation ◽  
Using Data ◽  
Image Position ◽  
Neutral Mutation Rate

SUMMARYThe ‘neutral mutation theory’ holds that most amino acid substitutions in evolution are selectively neutral. The known pattern of variation in human haemoglobins can only be made consistent with this theory if the human species has passed through a bottleneck of numbers in the recent past. If this theory is true, estimates of the necessary size and duration of this bottleneck can be made. A theory is developed which leads to an estimate of Yg, n, the number of alleles present in a population which arise between g and n generations ago, and hence to the estimatewhere u is the neutral mutation rate and Ne the effective population size, for the probability that a population contains no such alleles. Using data on haemoglobins, this gives an approximate upper limit to the time elapsed since the bottleneck in human numbers. Either such a bottleneck occurred, or the neutral mutation theory is false; data on other proteins will enable a choice between these possibilities to be made.

scholarly journals A study on a nearly neutral mutation model in finite populations.

Genetics ◽  
1991 ◽  
Vol 128 (1) ◽  
pp. 183-192
Author(s):  
H Tachida
Keyword(s):  
Standard Deviation ◽  
Equilibrium State ◽  
Mutation Rate ◽  
Selection Coefficient ◽  
Average Heterozygosity ◽  
Finite Populations ◽  
Mutation Model ◽  
Neutral Mutation ◽  
Mutant Effect ◽  
The Relationship

Abstract As a nearly neutral mutation model, the house-of-cards model is studied in finite populations using computer simulations. The distribution of the mutant effect is assumed to be normal. The behavior is mainly determined by the product of the population size, N, and the standard deviation, sigma, of the distribution of the mutant effect. If 4N sigma is large compared to one, a few advantageous mutants are quickly fixed in early generations. Then most mutation becomes deleterious and very slow increase of the average selection coefficient follows. It takes very long for the population to reach the equilibrium state. Substitutions of alleles occur very infrequently in the later stage. If 4N sigma is the order of one or less, the behavior is qualitatively similar to that of the strict neutral case. Gradual increase of the average selection coefficient occurs and in generations of several times the inverse of the mutation rate the population almost reaches the equilibrium state. Both advantageous and neutral (including slightly deleterious) mutations are fixed. Except in the early stage, an increase of the standard deviation of the distribution of the mutant effect decreases the average heterozygosity. The substitution rate is reduced as 4N sigma is increased. Three tests of neutrality, one using the relationship between the average and the variance of heterozygosity, another using the relationship between the average heterozygosity and the average number of substitutions and Watterson's homozygosity test are applied to the consequences of the present model. It is found that deviation from the neutral expectation becomes apparent only when 4N sigma is more than two. Also a simple approximation for the model is developed which works well when the mutation rate is very small.

scholarly journals The impact of ancestral population size and incomplete lineage sorting on Bayesian estimation of species divergence times

2015 ◽  
Vol 61 (5) ◽  
pp. 874-885 ◽  
Author(s):  
Konstantinos Angelis ◽  
Mario Dos Reis
Keyword(s):  
Population Size ◽  
Mutation Rate ◽  
Incomplete Lineage Sorting ◽  
Internal Node ◽  
Ancestral Population ◽  
Divergence Times ◽  
Lineage Sorting ◽  
Species Divergence ◽  
Coalescent Process ◽  
The Impact

Abstract Although the effects of the coalescent process on sequence divergence and genealogies are well understood, the virtual majority of studies that use molecular sequences to estimate times of divergence among species have failed to account for the coalescent process. Here we study the impact of ancestral population size and incomplete lineage sorting on Bayesian estimates of species divergence times under the molecular clock when the inference model ignores the coalescent process. Using a combination of mathematical analysis, computer simulations and analysis of real data, we find that the errors on estimates of times and the molecular rate can be substantial when ancestral populations are large and when there is substantial incomplete lineage sorting. For example, in a simple three-species case, we find that if the most precise fossil calibration is placed on the root of the phylogeny, the age of the internal node is overestimated, while if the most precise calibration is placed on the internal node, then the age of the root is underestimated. In both cases, the molecular rate is overestimated. Using simulations on a phylogeny of nine species, we show that substantial errors in time and rate estimates can be obtained even when dating ancient divergence events. We analyse the hominoid phylogeny and show that estimates of the neutral mutation rate obtained while ignoring the coalescent are too high. Using a coalescent-based technique to obtain geological times of divergence, we obtain estimates of the mutation rate that are within experimental estimates and we also obtain substantially older divergence times within the phylogeny.

Sign in / Sign up

Export Citation Format

Share Document