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

Summary Recent 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 Implementation Trevolver is implemented in Perl and available on GitHub under GNU General Public License (GPL) version 3 at https://github.com/chasewnelson/trevolver . Contact [email protected] Supplementary information Further details and example data are available on GitHub.