Theory of prokaryotic genome evolution

Abstract

Bacteria and archaea typically possess small genomes that are tightly packed with protein-coding genes. The compactness of prokaryotic genomes is commonly perceived as evidence of adaptive genome streamlining caused by strong purifying selection in large microbial populations. In such populations, even the small cost incurred by nonfunctional DNA because of extra energy and time expenditure is thought to be sufficient for this extra genetic material to be eliminated by selection. However, contrary to the predictions of this model, there exists a consistent, positive correlation between the strength of selection at the protein sequence level, measured as the ratio of nonsynonymous to synonymous substitution rates, and microbial genome size. Here, by fitting the genome size distributions in multiple groups of prokaryotes to predictions of mathematical models of population evolution, we show that only models in which acquisition of additional genes is, on average, slightly beneficial yield a good fit to genomic data. These results suggest that the number of genes in prokaryotic genomes reflects the equilibrium between the benefit of additional genes that diminishes as the genome grows and deletion bias (i.e., the rate of deletion of genetic material being slightly greater than the rate of acquisition). Thus, new genes acquired by microbial genomes, on average, appear to be adaptive. The tight spacing of protein-coding genes likely results from a combination of the deletion bias and purifying selection that efficiently eliminates nonfunctional, noncoding sequences. T he majority of bacterial and archaeal genomes are small, at least compared with the genomes of multicellular and many unicellular eukaryotes (1, 2). Also, with the exception of deteriorating genomes of some parasitic bacteria, the prokaryotic genomes are highly compact, with densely packed protein-coding genes and a low fraction of noncoding sequences (3). The small genome size is thought to be selected for fast replication, whereas the high gene density additionally facilitates coregulation of gene expression via the operon organization (4, 5). Across the full range of cellular life forms, a significant positive correlation has been shown to exist between genome size and N e u, where N e is the effective population size, and u is the mutation rate per nucleotide (6-9). Accordingly, a simple and appealing population genetic theory has been developed, under which selection strength controls genome size and complexity (6, 9). Prokaryotes, with the exception of some parasites, have large effective population sizes on the order of 10 9 or even higher, which implies strong selection enabling prokaryotes to maintain compact genomes (10). Under this strong selection regime, even short nonfunctional sequences incur cost that is "visible" to selection, conceivably through a combination of increasing energy expenditure and reducing the replication rate, and are efficiently weeded out (11). In eukaryotes, at least the multicellular forms, the effective population ...

Disentangling the effects of selection and loss bias on gene dynamics

“…The intrinsic bias toward DNA deletion (and hence gene loss) that characterizes mutational processes in prokaryotes (as well as eukaryotes) results in nonadaptive genome reduction (13), whereas selection contributes to maintaining slightly beneficial genes (14). In agreement with this model, the strength of purifying selection, as measured by the ratio of nonsynonymous to synonymous variation, positively correlates with the genome size (15,16).…”

“…For the purpose of evolutionary analyses, a meaningful proxy for such an average can be obtained by inferring selection coefficients directly from the gene family abundances observed in large collections of genomes. The main difficulty in this case is disentangling the effects of selection from the effects of intrinsic loss bias, which normally requires a priori knowledge of the effective population size or the gene gain and loss rates (14,22,23).…”

Why prokaryotes have pangenomes

“…Clearly a neutral model for pangenome accrual will not work. In any case, recent simulation work has shown that, on average, HGTs in prokaryotes tend to be adaptive 30 .…”

“…Additionally the knock-on effect would be to promote the evolution of lower HGT rates 25 . It is clear that HGT rates, at least in some organisms, are quite high 30 , suggesting that HGT is not always deleterious.…”

Profile of Eugene V. Koonin

“…In his Inaugural Article, Koonin describes the contributions of one of these models (12). "Microbial genomes are extremely streamlined," he says.…”