Modeling the mosaic structure of bacterial genomes to infer their evolutionary history

Abstract

The timing and phylogeny of bacterial evolution is difficult to reconstruct because of a scarce fossil record, deep genomic divergences and complexities associated with molecular clocks. Studying bacterial evolutionary history using rich and rapidly accumulating genomic data requires accurate modeling of genome evolution, taking into account that different parts of bacterial genomes have different history. In particular, along the genome, different loci are subject to different selective pressure. In addition, some are horizontally transferred from one bacterium to another, resulting in a mosaic-like genome structure. An important technical aspect is that loci with high effective mutation rates can diverge beyond the aligner detection limit, biasing the genome-wide divergence estimate towards more conserved loci. Therefore, the genome-wide molecular clock cannot be directly applied to study bacterial evolutionary history. In this article, we propose a novel method to gain insight into bacterial evolution based on statistical properties of genomic sequences comparisons. The length distribution of the sequence matches is shaped by the effective mutation rates of different loci, by the horizontal transfers and by the aligner sensitivity. Based on these inputs we build a model and demonstrate that it accounts for the empirically observed distributions, taking the Enterobacteriaceae family as an example. Using the model and the empirical data we fit the evolutionary parameters: time divergences and horizontal transfer rates. Based on the estimated time divergences we build a time-calibrated phylogenetic tree, demonstrating the accuracy of the method and its ability to unravel vertical and horizontal transfers in bacterial genomes.