progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement

Abstract

BackgroundMultiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms.Methodology/Principal FindingsWe describe a new method to align two or more genomes that have undergone rearrangements due to recombination and substantial amounts of segmental gain and loss (flux). We demonstrate that the new method can accurately align regions conserved in some, but not all, of the genomes, an important case not handled by our previous work. The method uses a novel alignment objective score called a sum-of-pairs breakpoint score, which facilitates accurate detection of rearrangement breakpoints when genomes have unequal gene content. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The new genome alignment algorithm demonstrates high accuracy in situations where genomes have undergone biologically feasible amounts of genome rearrangement, segmental gain and loss. We apply the new algorithm to a set of 23 genomes from the genera Escherichia, Shigella, and Salmonella. Analysis of whole-genome multiple alignments allows us to extend the previously defined concepts of core- and pan-genomes to include not only annotated genes, but also non-coding regions with potential regulatory roles. The 23 enterobacteria have an estimated core-genome of 2.46Mbp conserved among all taxa and a pan-genome of 15.2Mbp. We document substantial population-level variability among these organisms driven by segmental gain and loss. Interestingly, much variability lies in intergenic regions, suggesting that the Enterobacteriacae may exhibit regulatory divergence.ConclusionsThe multiple genome alignments generated by our software provide a platform for comparative genomic and population genomic studies. Free, open-source software implementing the described genome alignment approach is available from http://gel.ahabs.wisc.edu/mauve.

Microbial metabolisms in a 2.5-km-deep ecosystem created by hydraulic fracturing in shales

“…To determine if the same genome was present in different time points, we calculated ANI values (http://enve-omics.ce.gatech.edu/ani/) using a two-way ANI, with ≥99% ANI considered an initial cutoff for identical genomes through time. For genera with ≥99% ANI values (Arcobacter, Halanaerobium and Idiomarina), we then aligned contigs to examine synteny using the progressive Mauve aligner 44 in Geneious R8 (ref. 45).…”

Evolutionary genomics of the cold-adapted diatom Fragilariopsis cylindrus

“…We obtained alignments of 210 smaller scaffolds against larger scaffolds, with a total length of 15.9 Mb and an alignment coverage over the entire length of the smaller scaffold for 74.3% of the alignments. Syntenic scaffolds that were homologous over the entire length were analysed using Mauve genome alignment software 62 . Gene models of the aligned smaller scaffolds, which formed the best bi-directional blastn hit pairs with corresponding genes on larger scaffolds and > 90% nucleotide identity were removed to produce a final non-redundant protein-coding gene model set.…”

The quest to resolve recent radiations: Plastid phylogenomics of extinct and endangered Hawaiian endemic mints (Lamiaceae)

“…We used Mauve 2.3.1 (Darling et al, 2010) to compare the structure and similarity of the mint genome sequences to each other and to 13 available Lamiales chloroplast genomes: Ajuga reptans (NC_023102), Andrographis paniculata (NC_022451), Boea hygrometrica (NC_016468), Jasminum nudiflorum (NC_008407), Lindenbergia philippensis (NC_022859), Olea_europaea (NC_013707), Origanum vulgare (JX880022), Pinguicula ehlersiae (NC_023463), Salvia miltiorrhiza (NC_020431), Schwalbea americana (NC_023115), Sesamum_indicum (NC_016433), Tectona grandis (NC_020098), and Utricularia gibba (NC_021449). For all analyses we set the gap opening penalty to -200 and the gap extension penalty to -30.…”