Drift, Mutation, and the Origin of Cellular Features*

Although natural selection may be the most powerful force in the biological world, it is not all powerful. As a consequence, many aspects of genomic evolution can only be explained by the inability of natural selection to operate. This general principle extends to numerous cellular features, e.g., genomic mutation rates; transcription error rates; the multimeric states of proteins; and the phylogenetic drift of gene-regulatory vocabulary.

A fundamental principle is that although natural selection relentlessly pushes traits to the highest possible level of refinement, the limits to perfection are defined by the power of random genetic drift. This drift-barrier hypothesis broadly implies that the population-genetic environment imposes a fundamental constraint on the paths that are open vs. closed for evolutionary exploration in different phylogenetic lineages, hence defining the possible patterns of adaptation seen at the molecular and cellular level.

With these principles in mind, an attempt will be made to describe how two diverse sets scaling relationships – phylogenetic variation in error rates at the level of DNA and RNA, and in the maximum growth potential of species – can be explained at the theoretical level. With an increase in organism size, there is a decline in the effective population sizes of species, leading to a 1000-fold increase in the role of stochasticity in gene transmission. This, in turn, imposes a corresponding 1000-fold reduction in the range of selection coefficients visible to the eyes of natural selection, such that species with small cells are capable of exploiting/eradicating very fine-scale mutations. In contrast, selection operates in a much more granular way in large-celled species, which are insensitive to large insertions of DNA and experience passive increases in genome size.