In silico Evolution and Comparative Genomic Analysis of IncX3 Plasmids Isolated From China Over Ten Years

IncX3 plasmids are correlated with the dissemination and acquisition of carbapenem resistance in Enterobacteriaceae and have been prevalent in China over the last 10 years. Since the distribution characteristics of IncX3 plasmids across China as well as their evolutionary traits for 10 years remain unclear, here we conducted a retrospective literature review and in silico comparative analysis of IncX3 plasmids in publicly available IncX3 plasmid genomes. IncX3 plasmids distributed in 17 provinces or cities were extracted for analysis, which tend to be specifically associated with hospital-isolated Escherichia coli ST410 from phylogroup A. Although the backbones of IncX3 plasmids have remained highly conservative over the last 10 years, the blaNDM resistance genetic contexts on these plasmids could fall into five subtypes, among which AR_N1_I has been identified in Enterobacter cloacae174 chromosome and AR_N5_I was simultaneously located on IncF and IncA/C plasmids. This suggests that the blaNDM resistance gene environment can spread between different plasmids, between different bacterial genera, or between strains and plasmids, highlighting that it is imperative to adopt more stringent infection control measures targeting IncX3 plasmid spread.

The role of structural pleiotropy and regulatory evolution in the retention of heteromers of paralogs

Gene duplication is a driver of the evolution of new functions. The duplication of genes encoding homomeric proteins leads to the formation of homomers and heteromers of paralogs, creating new complexes after a single duplication event. The loss of these heteromers may be required for the two paralogs to evolve independent functions. Using yeast as a model, we find that heteromerization is frequent among duplicated homomers and correlates with functional similarity between paralogs. Using in silico evolution, we show that for homomers and heteromers sharing binding interfaces, mutations in one paralog can have structural pleiotropic effects on both interactions, resulting in highly correlated responses of the complexes to selection. Therefore, heteromerization could be preserved indirectly due to selection for the maintenance of homomers, thus slowing down functional divergence between paralogs. We suggest that paralogs can overcome the obstacle of structural pleiotropy by regulatory evolution at the transcriptional and post-translational levels.

Architecture and coevolution of allosteric materials

We introduce a numerical scheme to evolve functional elastic materials that can accomplish a specified mechanical task. In this scheme, the number of solutions, their spatial architectures, and the correlations among them can be computed. As an example, we consider an “allosteric” task, which requires the material to respond specifically to a stimulus at a distant active site. We find that functioning materials evolve a less-constrained trumpet-shaped region connecting the stimulus and active sites, and that the amplitude of the elastic response varies nonmonotonically along the trumpet. As previously shown for some proteins, we find that correlations appearing during evolution alone are sufficient to identify key aspects of this design. Finally, we show that the success of this architecture stems from the emergence of soft edge modes recently found to appear near the surface of marginally connected materials. Overall, our in silico evolution experiment offers a window to study the relationship between structure, function, and correlations emerging during evolution.