Trevolver: simulating non-reversible DNA sequence evolution in trinucleotide context on a bifurcating tree

SummaryRecent de novo mutation data allow the estimation of non-reversible mutation rates for trinucleotide sequence contexts. However, existing tools for simulating DNA sequence evolution are limited to time-reversible models or do not consider trinucleotide context-dependent rates. As this ability is critical to testing evolutionary scenarios under neutrality, we created Trevolver. Sequence evolution is simulated on a bifurcating tree using a 64 × 4 trinucleotide mutation model. Runtime is fast and results match theoretical expectation for CpG sites. Simulations with Trevolver will enable neutral hypotheses to be tested at within-species (polymorphism), between-species (divergence), within-host (e.g., viral evolution), and somatic (e.g., cancer) levels of evolutionary change.Availability and ImplementationTrevolver is implemented in Perl and available on GitHub under GNU General Public License (GPL) version 3 at https://github.com/chasewnelson/[email protected] informationFurther details and example data are available on GitHub.

The Effects of Hill-Robertson Interference Between Weakly Selected Mutations on Patterns of Molecular Evolution and Variation

Associations between selected alleles and the genetic backgrounds on which they are found can reduce the efficacy of selection. We consider the extent to which such interference, known as the Hill-Robertson effect, acting between weakly selected alleles, can restrict molecular adaptation and affect patterns of polymorphism and divergence. In particular, we focus on synonymous-site mutations, considering the fate of novel variants in a two-locus model and the equilibrium effects of interference with multiple loci and reversible mutation. We find that weak selection Hill-Robertson (wsHR) interference can considerably reduce adaptation, e.g., codon bias, and, to a lesser extent, levels of polymorphism, particularly in regions of low recombination. Interference causes the frequency distribution of segregating sites to resemble that expected from more weakly selected mutations and also generates specific patterns of linkage disequilibrium. While the selection coefficients involved are small, the fitness consequences of wsHR interference across the genome can be considerable. We suggest that wsHR interference is an important force in the evolution of nonrecombining genomes and may explain the unexpected constancy of codon bias across species of very different census population sizes, as well as several unusual features of codon usage in Drosophila.

MUTATION, A MICROCOMPUTER MODULE DESIGNED FOR PLANT BREEDING AND GENETICS

A teaching module was developed for computer-aided instruction of mutation theory. The Hypercard-driven, Macintosh compatible module illustrates the concepts of: 1) Changes in allele frequency with mutation pressure; 2) Number of alleles maintained in populations, and; 3) The Neutrality Hypothesis. The concepts are integrated in an application by using a game format. Mutation is the ultimate source of genetic variation. Mutation pressure results in changes in allele frequency. Concept 1 illustrates the theoretical changes in allele frequency under pressure of reversible mutation. Mutation equilibrium is depicted as P=V/u+v; where v=mutation rates of allele A and u of allele a. The Infinite-Alleles Model of mutation is illustrated in Concept 2 and specifies characteristics of new mutations by F=1/4Nu+1, where F=fixation index and N=number in population. Concept 3 demonstrates the hypothesis that polymorphisms result from selectively neutral alleles maintained in a balance between mutation and random genetic drift.

MUTATION, A MICROCOMPUTER MODULE DESIGNED FOR PLANT BREEDING AND GENETICS

A teaching module was developed for computer-aided instruction of mutation theory. The Hypercard-driven, Macintosh compatible module illustrates the concepts of: 1) Changes in allele frequency with mutation pressure; 2) Number of alleles maintained in populations, and; 3) The Neutrality Hypothesis. The concepts are integrated in an application by using a game format.Mutation is the ultimate source of genetic variation. Mutation pressure results in changes in allele frequency. Concept 1 illustrates the theoretical changes in allele frequency under pressure of reversible mutation. Mutation equilibrium is depicted as P=V/u+v; where v=mutation rates of allele A and u of allele a. The Infinite-Alleles Model of mutation is illustrated in Concept 2 and specifies characteristics of new mutations by F=1/4Nu+1, where F=fixation index and N=number in population. Concept 3 demonstrates the hypothesis that polymorphisms result from selectively neutral alleles maintained in a balance between mutation and random genetic drift.