Did group selection play a role in the evolution of plasmid endosymbiosis?

May 16, 2013 by Eric Bolo

Bacterial plasmids are nucleotide sequences floating in the cytoplasm of bacteria. These molecules replicate independently from the main chromosomal DNA and are not essential to the survival or replication of their host. Plasmids are thought to be part of the bacterial domain’s mobilome (for overview, see Siefert, 2009), a sort of genetic commonwealth which most, if not all, bacterial cells can pull from, incorporate and express. Plasmids can replicate inside a host and then move to another cell via horizontal genetic transfer (HGT), a term denoting various mechanism of incorporation of exogenous genetic material.



Of these mechanisms, two are relevant to plasmids:

transformation – the uptake of genetic material in the cell’s surrounding environment through its membrane, and conjugation – the direct transfer of genetic material via cell-to-cell contact.

Interestingly, in the case of conjugation, most plasmid-carrying cells have mechanisms to detect whether a potential recipient cell already carries the plasmid to be transferred, and initiate transfer only if it does not. Horizontal genetic transfer plays a role similar for bacteria as sexual reproduction does for sexually differentiated forms of life by increasing genetic variability and thus evolutive potential. Most plasmids are endosymbionts to their host cell and may serve, among other functions, to foster antibiotic resistance as well as cause benign bacterial strains to become virulent. Other plasmids, however, parasitize their host and degrade cell function and fitness.

Endosymbionts: evolution of cooperation

Endosymbiotic plasmids provide an interesting case study for inquiring into the evolution of cooperation. For instance, in his 2002 paper that I mentioned earlier, Paulsson claims that replication control by plasmids is the product of group selection – if plasmids are seen as the individuals and the host cell as the group. If plasmids replicated up to the cell’s carrying capacity, they would increase their chance of fixing in the descendant cells relative to their cell mates but would significantly hamper their host. Viewed from a group selection standpoint, within-group selection should then favor “selfishness” –- high replication rate –- while between-group selection should favor limited replication — “altruism”. By controlling their replication below carrying capacity via a sophisticated feedback system involving plasmid-encoded replication activators and inhibitors, many plasmids have struck a balance between these opposite selection gradients. (Paulsson, 2002)

A few weeks ago I gave a presentation on Paulsson’s paper about plasmid group selection for the EGT group, at the end of which Artem suggested that we build a game theoretical model to better understand, and generalize, the mechanisms at play behind plasmid replication control. To be honest, I am only beginning to dabble with game theory, so I am unsure exactly where our work is leading to. But it is nevertheless clear to me that before building any such model, we should understand the basics of how plasmids replicate within a cell and how they split at cell division, for these two mechanisms — replication and partition — greatly influence plasmid fitness.

Replication control

To be maintained across generations of bacterial cells, plasmids must ensure that they replicate at least once during the life cycle of their host. As a result, most plasmids have evolved systems to enable and control their replication. Some plasmids replicate only once at each cell cycle, as is the case of the prototypical plasmid, the F-plasmid; others replicate many times per cycle. Many plasmids control their replication via a feedback system in which activators promote replication and inhibitors contain it. In the case of two well-studied plasmids, R1 and ColE1, activators can act in cis – in which case the cis sequence is usually neighboring the replication initiation sequence and affects only that sequence – or in in trans – in which case the trans sequence affects the initiation sequences of all activator-sensitive plasmids in the cell (note that plasmids of different types are not necessarily insensitive to other plasmids’ activators/inhibitors; more about that in the penultimate paragraph). Inhibitors, by contrast, act only in trans. The distinction between cis and trans is an important one, because any mutation to a trans activator will be “public” to all activator-sensitive plasmids in the cell, whereas cis activators/inhibitors mutations will be private to the mutant. (Paulsson 2002)

Partition control

Not only must plasmids secure their replication, they must also ensure that, once replicated, the plasmids will be split in the daughter cells in such a way that each daughter contains at least one plasmid copy. For instance, in the case of the F-plasmid, since the latter replicates only once, the partition control mechanism has to ensure, and does, that each daughter contains exactly one copy. Unlike the partitioning of chromosomal DNA during cell mitosis, which was first observed at the end of the nineteenth century and is now well understood, the precise mechanisms of plasmid partitioning largely remain a mystery. Some hints have recently been uncovered, however. A few studies have shown that some plasmids use a mechanical system similar to that which partitions chromosomes during mitosis. Where that is case, plasmids are tethered to each pole of the dividing cell with protein “strings” or tubular structures that pull sister plasmids apart as the host divides. But it has recently been suggested that the dominant mechanism for plasmid partitioning might be molecular rather than mechanical in nature. For low-copy number plasmids, especially, some authors have shown that plasmids encode Par ATPases, <proteins built around the Walker A amino-acid sequence motif that ensure effective partition (Sherratt 2013). I won’t delve into this further here, mostly because I know so little about the subject, and also because I intend to deepen this discussion in future posts.

Incompatibility

Many plasmids are incompatible with each other, meaning that when both are present in a given host, one of the two will fixate at the expense of the other. It is now known that such incompatibility is mainly due to mutual susceptibility to each plasmid’s replication and partition control system. Let us take the simple example of two plasmids, each of which has a characteristic copy number of 1. If the two plasmids share the same replication control mechanism, the latter will allow one of the two plasmids to replicate, but will then prevent any further replication. The losing plasmid will not be replicated, and will thus be found in only one of the daughter cells. (Novick, 1987)

This post was meant to sketch the very basics of the dynamics affecting plasmid replication and partition. Plasmids have sophisticated mechanisms for controlling replication and partition and ensuring their viability down bacterial cell lines. Although the details of these control systems are often still shrouded in mystery, the little we know of them should enable us to sketch a simple yet plausible model of plasmid cooperation.

References

Novick, R.P. (1987) Plasmid incompatibility. Microbiological Reviews, 51-4: 381-395

Paulsson J (2002). Multileveled selection on plasmid replication. Genetics, 161 (4), 1373-84 PMID: 12238464

Siefert, J. L. (2009). Defining the mobilome. In Horizontal Gene Transfer (pp. 13-27). Humana Press.

Sherratt, D. (2013) Plasmid partition: sisters drifing apart. The EMBO Journal, 32:1208-1210