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Transcriptional regulation is crucial for all biological processes and well investigated at the molecular level for a wide range of organisms. However, it is quite unclear how innovations, such as the activity of a novel regulatory element, evolve. In the case of transcription factor (TF) binding, both a novel TF and a novel-binding site would need to evolve concertedly. Since promiscuous functions have recently been identified as important intermediate steps in creating novel specific functions in many areas such as enzyme evolution and protein–protein interactions, we ask here how promiscuous binding of TFs to TF-binding sites (TFBSs) affects the robustness and evolvability of this tightly regulated system. Specifically, we investigate the binding behavior of several hundred TFs from different species at unprecedented breadth. Our results illustrate multiple aspects of TF-binding interactions, ranging from correlations between the strength of the interaction bond and specificity, to preferences regarding TFBS nucleotide composition in relation to both domains and binding specificity. We identified a subset of high A/T binding motifs. Motifs in this subset had many functionally neutral one-error mutants, and were bound by multiple different binding domains. Our results indicate that, especially for some TF–TFBS associations, low binding specificity confers high degrees of evolvability, that is that few mutations facilitate rapid changes in transcriptional regulation, in particular for large and old TF families. In this study we identify binding motifs exhibiting behavior indicating high evolutionary potential for innovations in transcriptional regulation. [ABSTRACT FROM AUTHOR]

Abstract: We analyze here the evolutionary consequences of selection with delay in a population genetics context. In the classical works on evolutionary dynamics, an individual produces off-springs in direct proportion to its fitness, a process in which mutations may occur. In the present scenario of delayed selection, individuals that acquire deleterious mutations can still reproduce unharmed for several generations. During this time delay, the damage passed on to off-springs can potentially be repaired by subsequent compensatory mutations. In the absence of such a repair, the individual becomes sterile. Here we study the population-genetic effects of such a time delay by means of both numerical simulations and theoretical modeling. The results show that delayed selection lowers the extinction threshold, endangering the survival of the population. Surprisingly, however, no traces of this delay effect are encountered in the sequence diversity of the population. These conclusions suggest that delayed selection is hard to detect in genetic data and thus could be a wide-spread but rarely detected phenomenon. [Copyright &y& Elsevier]

After an ancestral population splits into two allopatric populations, different mutations may fix in each. When pairs of mutations are brought together in a hybrid offspring, epistasis may cause reduced fitness. Such pairs are known as Bateson–Dobzhansky–Muller (BDM) incompatibilities. A well-known model of BDM incompatibility due to Orr suggests that the fitness load on hybrids should initially accelerate, and continue to increase as the number of potentially incompatible substitutions increases (the “snowball effect”). In the gene networks model, which violates a key assumption of Orr's model (independence of fixation probabilities), the snowball effect often does not occur. Instead, we describe three possible dynamics in a constant environment: (1) Stabilizing selection can constrain two allopatric populations to remain near-perfectly compatible. (2) Despite constancy of environment, punctuated evolution may obtain; populations may experience rare adaptations asynchronously, permitting incompatibility. (3) Despite stabilizing selection, developmental system drift may permit genetic change, allowing two populations to drift in and out of compatibility. We reinterpret Orr's model in terms of genetic distance. We extend Orr's model to the finite loci case, which can limit incompatibility. Finally, we suggest that neutral evolution of gene regulation in nature, to the point of speciation, is a distinct possibility. [ABSTRACT FROM AUTHOR]

It is often assumed that the efficiency of selection for mutational robustness would be proportional to mutation rate and population size, thus being inefficient in small populations. However, Krakauer and Plotkin (2002) hypothesized that selection in small populations would favor robustness mechanisms, such as redundancy, that mask the effect of deleterious mutations. In large populations, by contrast, selection is more effective at removing deleterious mutants and fitness would be improved by eliminating mechanisms that mask the effect of deleterious mutations and thus impede their removal. Here, we test whether these predictions are supported in experiments with evolving populations of digital organisms. Digital organisms are self-replicating programs that inhabit a virtual world inside a computer. Like their organic counterparts, digital organisms mutate, compete, evolve, and adapt by natural selection to their environment. In this study, 160 populations evolved at different combinations of mutation rate and population size. After 104 generations, we measured the mutational robustness of the most abundant genotype in each population. Mutational robustness tended to increase with mutation rate and to decline with population size, although the dependence with population size was in part mediated by a negative relationship between fitness and robustness. These results are independent of whether genomes were constrained to their original length or allowed to change in size. [ABSTRACT FROM AUTHOR]

Abstract: We investigate the evolutionary dynamics of a finite population of RNA sequences replicating on a neutral network. Despite the lack of differential fitness between viable sequences, we observe typical properties of adaptive evolution, such as increase of mean fitness over time and punctuated-equilibrium transitions, after initial mutation–selection balance has been reached. We find that a product of population size and mutation rate of approximately 30 or larger is sufficient to generate selection pressure for mutational robustness, even if the population size is orders of magnitude smaller than the neutral network on which the population resides. Our results show that quasispecies effects and neutral drift can occur concurrently, and that the relative importance of each is determined by the product of population size and mutation rate. [Copyright &y& Elsevier]