Rates of lateral gene transfer: high but why?

I just had a paper out which was an enlightening experience to write. Along with three Dutch co-authors, it was mainly a collaboration with Adam Eyre-Walker at Sussex (see this previous post). The manuscript morphed from a data paper into a ‘verbal theory’ (i.e. no equations) paper (I will spare you the details). To quote from the Abstract:

Lateral gene transfer (LGT) is of fundamental importance to the evolution of prokaryote genomes and has important practical consequences, as evidenced by the rapid dissemination of antibiotic resistance and virulence determinants. Relatively little effort has so far been devoted to explicitly quantifying the rate at which accessory genes are taken up and lost, but it is possible that the combined rate of lateral gene transfer and gene loss is higher than that of point mutation. What evolutionary forces underlie the rate of lateral gene transfer are not well understood. We here use theory developed to explain the evolution of mutation rates to address this question and explore its consequences for the study of prokaryote evolution.

Briefly, we first reviewed the (very few) studies that have quantified the rate at which prokaryote genomes change due to gene acquistion and loss. The relative dearth of data means that we do not know for sure, but it seems plausible that the rate at which whole genes are gained is on the order of point mutation or perhaps above that. Trying to work out the rate at which genomes changes due to uptake and loss of genes (relative to mutation) was inspired by another study where I found that very closely related Myxococcus genomes (see my personal page for some links to papers on this interesting bacterium) that differ only by several SNPs (point mutations) can differ by hundreds of genes. I was surprised by this finding. I asked a number of colleagues what they thought would happen first when a bacterial cell in the environment would divide for some time: a point mutation or a lateral gene transfer event/gene loss event. Almost all thought that point mutations would be more common. The fact that the Myxococcus isolates were very closely related is important. Most genomic changes are deleterious and will be removed by purifying selection. Comparing closely related genomes means that not enough time has passed for selection to have removed all (but the most severe) changes and thus results in missing many of them. Consistent with this expectation was that the ratio of gene content differences to point mutations decreased when comparing slightly less closely related Myxococcus isolates. (I hope to post about this other manuscript soon, it has been a long time coming and is still in revision at the moment.)

The second part of the paper is concerned with the question: why are changes in gene content so common in many bacterial species when most of them apparently seem deleterious? This question is quite fundamental to understanding bacterial genome evolution, including the evolution of pathogens. We discuss two main scenarios that could explain the high observed rates of lateral gene transfer. In the first scenario, the high rate of gene turnover is optimal: although the majority of LGT events are expected to be detrimental, this is outweighed by a small proportion of highly advantageous events. This is illustrated by the figure below:

Figure 2 CORRECTED PROOFS - CopyOn the x-axis, it shows the distribution of fitness effects (DFE). Mutations, as well as LGT events, have fitness effects that can be broadly divided into three categories. First, there are mutations that decrease fitness. Second, there are ‘neutral’ mutations, which have little or no effect on fitness. Third, there are advantageous mutations, which increase fitness by allowing organisms to adapt to their environment. However, in reality, there is a continuum of selective effects, stretching from those that are strongly deleterious, through weakly deleterious mutations, to neutral mutations and then on to mutations that are mildly or highly adaptive. The distribution of fitness effects refers to the relative frequencies of these types of mutation. We hypothesize that LGT events are generally subject to stronger positive and negative selection. In addition to the many LGT events that insert themselves into ‘native’ genes causing loss of function, result in the expression of proteins that are toxic to the cells or just are utterly useless and result in wastes of energy, there are also events that result in the uptake of whole genes or plasmids that allow for the immediate gain of new functions which could have strongly beneficial effects when adapting to a novel environment.

In the second scenario (I’ll keep it very brief, if you have read this far down you probably should turn to the actual paper), the rate of LGT is actually suboptimal but the fitness costs of preventing LGT events, often mediated by selfish genetic elements, are too high or barriers to gene transfer are impossible to achieve.


Vos M, Hesselman MC, Te Beek TA, Van Passel MWJ and Eyre-Walker A. “Rates of Lateral Gene Transfer in Prokaryotes: High but Why?.” Trends in Microbiology 23, no. 10 (2015): 598-605. cough, cough

P.S. this was the 100th blog post!

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