Evolutionary mechanisms that determine which bacterial genes are carried on plasmids

Abstract

The evolutionary pressures that determine the location (chromosomal or plasmid-borne) of bacterial genes are not fully understood. We investigate these pressures through mathematical modelling in the context of antibiotic resistance, which is often found on plasmids. Our central finding is that gene location is under positive frequency-dependent selection, which can keep moderately beneficial genes on plasmids, despite occasional plasmid loss. For these genes, positive frequency-dependence leads to a priority effect: whichever form is acquired first has time to increase in frequency and thus become difficult to displace. We therefore propose that some traits, including antibiotic resistance, are found on plasmids because they are typically acquired on plasmids. Gene flow between plasmid and chromosome allows chromosomal forms to arise, but positive frequency-dependent selection prevents these from establishing. We also re-visit some previous theory in light of our results, with implications for plasmid persistence and the role of local adaptation in plasmid dynamics.

Plasmid co-infection: linking biological mechanisms to ecological and evolutionary dynamics

“…If these systems are indeed as effective in vivo as in vitro data suggest, co-infection only occurs between plasmids of different exclusion groups and co-infected cells are therefore indeed not susceptible to displacement. Furthermore, when considering variants of the same backbone with and without a particular cargo gene, it is appropriate to exclude co-infection [11,83]. On the other hand, our results highlight that frequency-dependent effects also arise from other model features.…”

“…recombination [64,82]. Frequencydependent effects would also be expected to influence the mobility of genes between plasmids (or plasmid and chromosome [83]). For example, if the presence of the same cargo gene on (compatible) co-resident plasmids gives rise to negative epistasis between the plasmids (due to negative gene dosage effects), the resulting PFDS would constrain gene mobility: the disadvantage associated with low frequency variants would prevent plasmids that have newly acquired the cargo gene from increasing in frequency.…”

Plasmid co-infection: linking biological mechanisms to ecological and evolutionary dynamics

“…When present in the same cell, plasmids can exchange genetic material through for example, recombination [68,89]. Frequency-dependent effects would also be expected to influence the mobility of genes between plasmids (or plasmid and chromosome [43]). For example, if the presence of the same cargo gene on co-resident plasmids gives rise to negative epistasis between the plasmids (owing to negative gene dosage effects), the resulting PFDS would constrain gene mobility: the disadvantage associated with low frequency variants would prevent plasmids that have newly acquired the cargo gene from increasing in frequency.…”

“…Epistatic effects could also arise from interactions between plasmid cargo genes, e.g. diminishing returns epistasis, whereby the additional benefit of a cargo gene is lower in a fitter background (for instance with resistance genes for the same antibiotic on two different plasmids) [43].…”

Can mobile genetic elements rescue genes from extinction?

“…For example, does phage predation or natural competence result in the predictable persistence of certain genes that would be lost in the absence of these processes? Are these genes indeed non-essential genes that are, on average, only slightly beneficial (van Dijk et al 2020;Lehtinen et al 2020)? Although very small fitness differences have been notoriously difficult to detect (Wiser and Lenski 2015;Bataillon 2000), new experimental techniques like DNA barcoding (Blundell and Levy 2014;Ba et al 2019) and Hi-C metagenomics (Stevenson et al 2017;Hall et al 2017) may provide more data on which genes persist in complex microbial communities.…”