Abstract
BackgroundThe dual concepts of pan and core genomes have been widely adopted as means to assess the distribution of gene families within microbial species and genera. The core genome is the set of genes shared by a group of organisms; the pan genome is the set of all genes seen in any of these organisms. A variety of methods have provided drastically different estimates of the sizes of pan and core genomes from sequenced representatives of the same groups of bacteria.ResultsWe use a combination of mathematical, statistical and computational methods to show that current predictions of pan and core genome sizes may have no correspondence to true values. Pan and core genome size estimates are problematic because they depend on the estimation of the occurrence of rare genes and genomes, respectively, which are difficult to estimate precisely because they are rare. Instead, we introduce and evaluate a robust metric - genomic fluidity - to categorize the gene-level similarity among groups of sequenced isolates. Genomic fluidity is a measure of the dissimilarity of genomes evaluated at the gene level.ConclusionsThe genomic fluidity of a population can be estimated accurately given a small number of sequenced genomes. Further, the genomic fluidity of groups of organisms can be compared robustly despite variation in algorithms used to identify genes and their homologs. As such, we recommend that genomic fluidity be used in place of pan and core genome size estimates when assessing gene diversity within genomes of a species or a group of closely related organisms.
Highlights
The dual concepts of pan and core genomes have been widely adopted as means to assess the distribution of gene families within microbial species and genera
A gene that only appears in 0.00001% of genomes (1 in 107 occurrence) contributes as much to the pan genome as does a core gene (Figure 1A), the rare gene will almost certainly not be detected in a sample set of tens or hundreds of sequenced genomes (Figure 1B)
Genomic fluidity is a robust and reliable estimator of gene diversity We propose the use of genomic fluidity, as a robust diversity metric which can be applied to small numbers of sequenced genomes whether at the species level or amongst groups of increasingly unrelated organisms
Summary
The dual concepts of pan and core genomes have been widely adopted as means to assess the distribution of gene families within microbial species and genera. A variety of methods have provided drastically different estimates of the sizes of pan and core genomes from sequenced representatives of the same groups of bacteria. Re-sequencing efforts have led to the following discovery: the representation of gene families in isolates from the same bacterial species is highly variable [5,6,7,8,9]. This variability poses conceptual as well as applied problems. Estimating the actual list of genes in the pan and core genomes remains intractable
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