Synonymous codon usage and selection on proteins

When mutation rates are low, natural selection remains effective, and increasing the mutation rate can give rise to an increase in adaptation rate. When mutation rates are high to begin with, however, increasing the mutation rate may have a detrimental effect because of the overwhelming presence of deleterious mutations. Indeed, if mutation rates are high enough: 1) adaptation rate can become negative despite the continued availability of adaptive and/or compensatory mutation...

The genetic code refers to a rule that maps 64 codons to 20 amino acids. Nearly all organisms, with few exceptions, share the same genetic code, the standard genetic code (SGC). While it remains unclear why this universal code has arisen and been maintained during evolution, it may have been preserved under selection pressure. Theoretical studies comparing the SGC and numerically created hypothetical random genetic codes have suggested that the SGC has been subject to strong ...

George Williams defined an evolutionary unit as hereditary information for which the selection bias between competing units dominates the informational decay caused by imperfect transmission. In this article, I extend Williams' approach to show that the ratio of selection bias to transmission bias provides a unifying framework for diverse biological problems. Specific examples include Haldane and Lande's mutation-selection balance, Eigen's error threshold and quasispecies, Va...

We give a overview of stochastic models of evolution that have found applications in genetics, ecology and linguistics for an audience of nonspecialists, especially statistical physicists. In particular, we focus mostly on neutral models in which no intrinsic advantage is ascribed to a particular type of the variable unit, for example a gene, appearing in the theory. In many cases these models are exactly solvable and furthermore go some way to describing observed features of...

Population genomic studies have shown that genetic draft and background selection can profoundly affect the genome-wide patterns of molecular variation. We performed forward simulations under realistic gene-structure and selection scenarios to investigate whether such linkage effects impinge on the ability of the McDonald-Kreitman (MK) test to infer the rate of positive selection (\alpha) from polymorphism and divergence data. We find that in the presence of slightly deleteri...

In considering evolution of transcribed regions, regulatory modules, and other genomic loci of interest, we are often faced with a situation in which the number of allelic states greatly exceeds the population size. In this limit, the population eventually adopts a steady state characterized by mutation-selection-drift balance. Although new alleles continue to be explored through mutation, the statistics of the population, and in particular the probabilities of seeing specifi...

Essential genes constitute the core of genes which cannot be mutated too much nor lost along the evolutionary history of a species. Natural selection is expected to be stricter on essential genes and on conserved (highly shared) genes, than on genes that are either nonessential or peculiar to a single or a few species. In order to further assess this expectation, we study here how essentiality of a gene is connected with its degree of conservation among several unrelated bact...

We present a computer simulation, which is inspired by Penna model, to help understanding the effect of genetic coding tables on population dynamics. To represent populations we used real and artificial gene sequences in this model. We coded these sequences using different amino acid tables in Nature, the standard table as well as the tables which are used by mithocondria and some eukaryotes. Contrary to common belief we find that the standard code table which is used in most...

An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a phenomenon known as epistasis. In a recent letter to Nature, Breen et al. (2012) argued that epistasis must be "pervasive throughout protein evolution" because the observed ratio between the per-site rates of non-synonymous and synonymous substitu...

The genetic code underlying protein synthesis is a canonical example of a degenerate biological system. Degeneracies in physical and biological systems can be lifted by external perturbations thus allowing degenerate systems to exhibit a wide range of behaviors. Here we show that the degeneracy of the genetic code is lifted by environmental perturbations to regulate protein levels in living cells. By measuring protein synthesis rates from a synthetic reporter library in Esche...