Computer Programs and Methodologies for the Simulation of DNA Sequence Data with Recombination

Miguel Arenas

doi:10.3389/fgene.2013.00009

Abstract

Computer simulations are useful in evolutionary biology for hypothesis testing, to verify analytical methods, to analyze interactions among evolutionary processes, and to estimate evolutionary parameters. In particular, the simulation of DNA sequences with recombination may help in understanding the role of recombination in diverse evolutionary questions, such as the genome structure. Consequently, plenty of computer simulators have been developed to simulate DNA sequence data with recombination. However, the choice of an appropriate tool, among all currently available simulators, is critical if recombination simulations are to be biologically meaningful. This review provides a practical survival guide to commonly used computer programs and methodologies for the simulation of coding and non-coding DNA sequences with recombination. It may help in the correct design of computer simulation experiments of recombination. In addition, the study includes a review of simulation studies investigating the impact of ignoring recombination when performing various evolutionary analyses, such as phylogenetic tree and ancestral sequence reconstructions. Alternative analytical methodologies accounting for recombination are also reviewed.

Highlights

Recombination constitutes a basic and dominant mechanism in molecular evolution, increasing genetic diversity before natural selection operates on the new sequence
This review provides a practical guide to the state of the art in software, and recommends methodologies, for simulating coding and non-coding sequence data with recombination, including recombination hotspots
Only three programs implement the direct simulation of coding data with recombination

Summary

INTRODUCTION

Recombination constitutes a basic and dominant mechanism in molecular evolution, increasing genetic diversity before natural selection operates on the new sequence. Programs like fastsimcoal (Excoffier and Foll, 2011) or mlcoalsim (Ramos-Onsins and Mitchell-Olds, 2007) allow for efficient simulations of non-coding genomic regions under recombination (including recombination hotspots) These tools do not implement a variety of substitution models (e.g., codon models), or particular evolutionary mechanisms like selection; this may be problematic if we are trying to mimic genome-wide data (see, Arbiza et al, 2011). A few programs currently implement the simulation of recombination hotspots, namely, SNPsim (Wiuf and Posada, 2003), cosi (Schaffner et al, 2005), GENOME (Liang et al, 2007), mbs (Teshima and Innan, 2009), and msHOT (Hellenthal and Stephens, 2007) All these programs simulate particular genetic markers (such as SNPs or STRs), DNA sequence evolution can be simulated upon phylogenetic trees produced by these programs if we use the two-step procedure described above.

Yes All

CONCLUSION