Bacterial plasmid-associated and chromosomal proteins have fundamentally different properties in protein interaction networks

Plasmids facilitate horizontal gene transfer, which enables the diversification of pathogens into new anatomical and environmental niches, implying that plasmid-encoded genes can cooperate well with chromosomal genes. We hypothesise that such mobile genes are functionally different to chromosomal ones due to this ability to encode non-essential functions like antimicrobial resistance and traverse distinct host cells. The effect of plasmid-driven gene gain on protein-protein interaction network topology is an important question in this area. Moreover, the extent to which these chromosomally- and plasmid-encoded proteins interact with proteins from their own groups compared to the levels with the other group remains unclear. Here, we examined the incidence and protein-protein interactions of all known plasmid-encoded genes across representative specimens from most bacteria using all available plasmids. We found that such plasmid-encoded genes constitute [~]0.7% of the total number of genes per bacterial sample, and that plasmid genes are preferentially associated with different species but had limited taxonomical power beyond this. Surprisingly, plasmid-encoded proteins had both more protein-protein interactions compared to chromosomal proteins, countering the hypothesis that genes with higher mobility rates should have fewer protein-level interactions. Nonetheless, topological analysis and investigation of the protein-protein interaction networks connectivity and change in the number of independent components demonstrated that the plasmid-encoded proteins had limited overall impact in >96% of samples. This paper assembled extensive data on plasmid-encoded proteins, their interactions and associations with diverse bacterial specimens that is available for the community to investigate in more detail. Significance statementIt is well-established that plasmids drive new traits in their bacterial hosts, but the extent to which host-plasmid co-evolution is evident at the level of protein-protein interactions remains unclear. To address this, we compiled and analysed all available valid bacterial plasmids and associated proteins to explore the compositional differences between chromosomal and plasmid-encoded proteins and their interaction levels. We found that plasmid-encoded genes were highly correlated across the bacterial samples such that they had a high association with taxonomic context. Contrasting with the complexity hypothesis, plasmid-encoded proteins had far more interactions on average than chromosomal ones, though they had minimal effects on protein-protein interaction network structure. This demonstrated that host-plasmid co-evolution is evident and detectable at the level of protein interactions.