The bioenergetic costs of a gene

Abstract

An enduring mystery of evolutionary genomics concerns the mechanisms responsible for lineage-specific expansions of genome size in eukaryotes, especially in multicellular species. One idea is that all excess DNA is mutationally hazardous, but weakly enough so that genome-size expansion passively emerges in species experiencing relatively low efficiency of selection owing to small effective population sizes. Another idea is that substantial gene additions were impossible without the energetic boost provided by the colonizing mitochondrion in the eukaryotic lineage. Contrary to this latter view, analysis of cellular energetics and genomics data from a wide variety of species indicates that, relative to the lifetime ATP requirements of a cell, the costs of a gene at the DNA, RNA, and protein levels decline with cell volume in both bacteria and eukaryotes. Moreover, these costs are usually sufficiently large to be perceived by natural selection in bacterial populations, but not in eukaryotes experiencing high levels of random genetic drift. Thus, for scaling reasons that are not yet understood, by virtue of their large size alone, eukaryotic cells are subject to a broader set of opportunities for the colonization of novel genes manifesting weakly advantageous or even transiently disadvantageous phenotypic effects. These results indicate that the origin of the mitochondrion was not a prerequisite for genome-size expansion. A lthough the idea that there is an intrinsic advantage to both cellular complexity and multicellularity is often taken to be self-evident, there is no direct evidence that either feature has been promoted by natural selection. Arriving at specific evidence to the contrary is also difficult, but plausible hypotheses based on mutation pressure and random genetic drift exist (1-3). Moreover, given that all extant organisms are temporally equidistant from the last universal common ancestor, the fact that multicellularity involving large numbers of cell types is only represented by two eukaryotic lineages (metazoans and land plants) raises additional questions about the global advantages of such body plans (1, 4). To help explain the absence of morphological complexity in prokaryotes, Lane and Martin (5) introduced the cost of a gene as an argument for the impossibility of high levels of cellular/developmental complexity without a power-generating mitochondrion, although an explicit evolutionary definition of such a cost was not provided.Regardless of the intrinsic advantages/disadvantages of cellular complexity, understanding the evolutionary mechanisms that promote vs. discourage the establishment of various cellular features ultimately requires insight into the energetic costs of such structures. Here, we focus specifically on the cumulative cost of a gene, subdividing this into expenses at the genomic, transcriptional, and protein levels. Although these issues have garnered some prior attention (6, 7), to put these costs into proper context, it is also necessary to understand the lifetime energetic...

Theory of prokaryotic genome evolution

“…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 size is substantially (by orders of magnitude) smaller, and consequently, selection is not strong enough to eliminate superfluous genetic material, which results in "bloated" genomes but also provides the raw material for the evolution of complex features (6)(7)(8).…”

Energetics and population genetics at the root of eukaryotic cellular and genomic complexity

“…Lynch and Marinov (1) show that the fitness cost of a new sequence negatively scales with the cell size, which is readily understandable because the energy cost does not necessarily strongly depend on the cell size, whereas the total energy expenditure is proportional to the cell volume. For a new sequence to be detected and eliminated by purifying selection from a haploid population, its cost should exceed 1/N e (where N e is effective population size).…”

“…In PNAS, Lynch and Marinov provide detailed estimates of the energy cost associated with the addition of new coding or noncoding sequences to prokaryotic and eukaryotic genomes (1). The amount of ATP that is expended at each step of information transfer is derived from the known biochemistry of these processes and an extensive collection of data on gene expression, as well as nucleic acid and protein decay for diverse organisms.…”

“…In addition to the sheer expansion, this genomic transformation included insertion of multiple introns into the protein-coding genes, disruption of operons, and linearization of chromosomes, which became possible thanks to the recruitment of the telomerase from a prokaryotic mobile element (9). The estimates of Lynch and Marinov (1) show that in and by itself the eukaryotic genome expansion did not require the energy production boost from the mitochondria.…”

“…Engulfment and domestication of an α-proteobacterium by a Loki-like archaeon could have led to substantially increased energy production per (chimeric) cell, which would trigger cell enlargement accompanied by intracellular compartmentalization. As shown by the estimates of Lynch and Marinov, a small population of large cells would have been conducive to the capture of substantial amounts of new DNA (1). Together with the onslaught of the endosymbiont DNA, this condition could have led to genome remodeling and expansion, molding the eukaryotic genomes (Fig.…”