Abstract
Genes and genomes do not evolve similarly in all branches of the tree of life. Detecting and characterizing the heterogeneity in time, and between lineages, of the nucleotide (or amino acid) substitution process is an important goal of current molecular evolutionary research. This task is typically achieved through the use of non-homogeneous models of sequence evolution, which being highly parametrized and computationally-demanding are not appropriate for large-scale analyses. Here we investigate an alternative methodological option based on probabilistic substitution mapping. The idea is to first reconstruct the substitutional history of each site of an alignment under a homogeneous model of sequence evolution, then to characterize variations in the substitution process across lineages based on substitution counts. Using simulated and published datasets, we demonstrate that probabilistic substitution mapping is robust in that it typically provides accurate reconstruction of sequence ancestry even when the true process is heterogeneous, but a homogeneous model is adopted. Consequently, we show that the new approach is essentially as efficient as and extremely faster than (up to 25 000 times) existing methods, thus paving the way for a systematic survey of substitution process heterogeneity across genes and lineages.
Highlights
Mapping the history of nucleotide or amino-acid changes onto the evolutionary history of a gene, as depicted by a phylogenetic tree, is of central interest to researchers in molecular evolution
Using simulations under realistic non-homogeneous models of substitutions, both at the nucleotide and codon level, we demonstrate that probabilistic substitution mapping is robust to the a priori choice of substitution model
Analyses of simulations at the codon level To test the robustness of substitution mapping, we propose to evaluate its ability to infer the dN/dS
Summary
Mapping the history of nucleotide or amino-acid changes onto the evolutionary history of a gene, as depicted by a phylogenetic tree, is of central interest to researchers in molecular evolution. This procedure, called mutation or substitution mapping, is useful for characterizing the molecular evolutionary processes of DNA and protein sequences, and their variations across sites and lineages. A substitution mapping method would take an alignment and a tree as input and return, as output, an estimate of the number/nature of substitutions that have occurred, for each site of the alignment and each branch of the tree. The ‘‘naive’’ substitution mapping procedure [8] involves first reconstructing all ancestral sequences at each node of the phylogenetic tree. The main drawback of such an approach is that it overlooks the uncertainty of the ancestral sequence inference
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