Novel metrics for quantifying bacterial genome composition skews

We present three novel metrics for quantifying bacterial genome composition skews. Skews are asymmetries in nucleotide usage that arise as a result of mutational biases and selective constraints, particularly for energy efficiency. The first two metrics (dot product and cross product of average skew vectors) evaluate sequence and gene annotation of the genome of a single species, while the third metric (regression RMSD) discovers patterns only discernable from studying genomes of thousands of species. The three metrics can be computed for genomes not yet finished and fully annotated. We studied the genomes of 7738 bacterial species, including completed genomes and partial drafts, and identified multiple species with unusual skew parameters. A number of these outliers (i.e., Borrelia, Ehrlichia, Kinetoplastibacterium, and Phytoplasma) display similar skew patterns despite a lack of phylogenetic relation. These disparate bacterial species share lifestyle characteristics, suggesting that our novel metrics successfully capture effects on genome composition of biosynthetic constraints and of interaction with the hosts. Introduction Bacterial genomes display significant compositional biases, both in terms of G+C content and in skews (strand asymmetry in ‘T’ vs. ‘A’ and ‘G’ vs. ‘C’ usage). These biases arise from the complex interplay of differential mutation rates and multiple selective constraints ​(Morton and Morton 2007; Vetsigian and Goldenfeld 2009)​, particularly for energy efficiency ​(Chen et al. 2016)​. Bacterial chromosomes are replicated in both directions, from the origin of replication site to the terminator site; the 1 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/176370 doi: bioRxiv preprint first posted online Aug. 15, 2017;