Predicting plasmid promiscuity based on genomic signature

Abstract

Despite the important contribution of self-transmissible plasmids to bacterial evolution, little is understood about the range of hosts in which these plasmids have evolved. Our goal was to infer this so-called evolutionary host range. The nucleotide composition, or genomic signature, of plasmids is often similar to that of the chromosome of their current host, suggesting that plasmids acquire their hosts' signature over time. Therefore, we examined whether the evolutionary host range of plasmids could be inferred by comparing their trinucleotide composition to that of all completely sequenced bacterial chromosomes. The diversity of candidate hosts was determined using taxonomic classification and genetic distance. The method was first tested using plasmids from six incompatibility (Inc) groups whose host ranges are generally thought to be narrow (IncF, IncH, and IncI) or broad (IncN, IncP, and IncW) and then applied to other plasmid groups. The evolutionary host range was found to be broad for IncP plasmids, narrow for IncF and IncI plasmids, and intermediate for IncH and IncN plasmids, which corresponds with their known host range. The IncW plasmids as well as several plasmids from the IncA/C, IncP, IncQ, IncU, and PromA groups have signatures that were not similar to any of the chromosomal signatures, raising the hypothesis that these plasmids have not been ameliorated in any host due to their promiscuous nature. The inferred evolutionary host range of IncA/C, IncP-9, and IncL/M plasmids requires further investigation. In this era of high-throughput sequencing, this genomic signature method is a useful tool for predicting the host range of novel mobile elements.

FIG. 1.

Hierarchical clustering of 55 plasmids based on their dissimilarities in gene content. In the matrix, columns are plasmids, rows are protein families, and black and white denote the presence and absence of each protein family, respectively. Each character (F, H, I, N, P, and W) denotes the incompatibility group to which each plasmid belongs.

FIG. 2.

A two-dimensional visualization of 55 plasmids using multidimensional scaling based on their dissimilarities in 3-mer genomic signature. Each character (F, H, I, N, P, and W) denotes the incompatibility (Inc) group to which each plasmid belongs.

FIG. 3.

Bar plot showing the number of candidate evolutionary hosts for each plasmid. Different colors indicate different taxonomic groups at the level of class (A) and order (B). The number of strains belonging to each taxon is given in parentheses. Each character (F, H, I, N, P, and W) denotes the incompatibility (Inc) group to which each plasmid belongs.

FIG. 4.

Box-and-whisker plots summarizing the distributions of diversity among candidate evolutionary hosts for plasmids from six incompatibility (Inc) groups (F, H, I, N, P, and W). The host diversity for each plasmid was quantified by the mean distance (Dmean) between all host pairs based on their dissimilarity in 16S rRNA gene sequence (A) and 3-mer genomic signature (B).