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, 2013) have each developed algorithms for using gene order for phylogenetic reconstruction. Furthermore, Lin et al. (2013) and Shifman et al. (2014) have used genome-wide gene order to produce phylogenetic trees. The later work produced a tree of 89 diverse microbial genomes using an algorithm for estimating average genome synteny (Shifman et al., 2014). In this study, we aimed to develop a simple computational method that could estimate a genome-wide gene order distance between two genomes (even when the genomes were highly diverged). Unlike many previous efforts, www.selleckchem.com/products/pf299804.html our intent was to have the gene order distance not rely on genes that are likely to be in the same operon (such as gene pairs). Here, we present a novel simple Monte Carlo method for estimating distributed gene order distances between genomes. In this method, we repeatedly randomly select six non-adjacent orthologs from each of two genomes and determine if the genes are Hamycin in the same order. The distances are then corrected using an adaptation of the Jukes-Cantor model to account for random gene order convergence. Materials and methods Initially, 143 prokaryotic genomes were analyzed (Table ?(Table1).1). This represented completed prokaryotic genomes available when the study began in January 2005. All genes from each genome were analyzed as queries using BLAST against each of the other genomes. Ortholog-pairs were identified as cases where two genes from different genomes were each other's BLAST best hit (top hit in both directions). This list of ortholog pairs served as the basis for both calculation of distributed gene order distances and the ortholog gene content distances. As defined by Snel et al. (1999), ortholog gene content similarity (S) was calculated as the number of ortholog pairs found for two genomes divided by the size of the smaller genome. this website This similarity was then converted to distance as equal to �Cln(S), as suggested by Korbel et al. (2002). However, using distance equal to 1-S gives similar correlation results. Table 1 143 taxa. Distributed gene order distances were determined using a novel Monte Carlo approach (Figure ?(Figure1).1). To determine the gene order distance between two genomes, first, six ortholog-pairs were randomly chosen. In order to limit orthologs being chosen from the same operon, the orthologs were required to be at least 5 genes away from each other in either genome. It was then determined if the chosen six ortholog-pairs were in the same order around both circular genomes (irrespective of each genes orientation). For organisms with multiple chromosomes, only the largest chromosome was used in this initial effort. This procedure was repeated for 100,000 iterations to establish one replicate sampling.