A synthetic theory of molecular evolution

According to the neo-Darwinian view of evolution evolution rate nu depends solely on the environment variation rate gamma, whereas in the non-Darwinian view evolution rate is determined mainly by the mutation rate mu. We have studied two kinds of population genetics models which exhibit both types of evolution in different parametric regions: one is a dynamical model representing infinite population, and the other is a Markov process model representing a nearly monomorphic finite population. In the infinite population model, after proving general time-derivative and mu-derivative formulas for the population average of quantitative traits, we show that if the mutation rate is adaptively determined, mu must be larger than nu in the stationary state. Loads of evolution are obtained in both regions. A high evolution rate such as nu = 1 per genome per generation is consistent with Haldane's value of tolerable load if and only if the functional constraint is not large and selection is weak, independent of whether the evolution is neo-Darwinian or non-Darwinian. As the selection intensity increases, nu is shown to change discontinuously from nearly mu to gamma at the transition point. In the finite population model, the transition of v is not discontinuous, but is very steep. On the other hand, no steep change of polymorphism takes place at the transition point. The steepness of the transition in our model suggests that real molecular evolution can be divided into either neo-Darwinian or non-Darwinian,and that the intermediate type of evolution is rather rare.     

The synthetic theory of evolution: general problems and the German contribution to the synthesis

Summary A metatheoretical and historiographical re-analysis of the Evolutionary Synthesis (the process) and the Synthetic Theory (the result) leads to the following conclusion: The Synthetic Theory is not a reductionistic, but rather a structuralistic theory with a limited range of relevant hierarchical levels. Historically the Synthesis was not a sudden event but a rational long-term project carried out between 1930 and 1950 by a large number of biologists in several countries. In the second part of our paper the contributions of several German biologists to the Synthesis are analyzed.     

A synthetic RNA-mediated evolution system in yeast

Laboratory evolution is a powerful approach to search for genetic adaptations to new or improved phenotypes, yet either relies on labour-intensive human-guided iterative rounds of mutagenesis and selection, or prolonged adaptation regimes based on naturally evolving cell populations. Here we present CRISPR- and RNA-assisted in vivo directed evolution (CRAIDE) of genomic loci using evolving chimeric donor gRNAs continuously delivered from an error-prone T7 RNA polymerase, and directly introduced as RNA repair donors into genomic targets under either Cas9 or dCas9 guidance. We validate CRAIDE by evolving novel functional variants of an auxotrophic marker gene, and by conferring resistance to a toxic amino acid analogue in baker''s yeast Saccharomyces cerevisiae with a mutation rate >3,000-fold higher compared to spontaneous native rate, thus enabling the first demonstrations of in vivo delivery and information transfer from long evolving RNA donor templates into genomic context without the use of in vitro supplied and pre-programmed repair donors.     

The theory of the evolution of dominance

Journal of Genetics - In a population which is mainly self-fertilized the majority of nonlethal mutant genes are present in homozygotes and very few in heterozygotes. The intensity of selection for...     

The evolution of synthetic oral drug properties

An analysis of the properties of 1791 synthetic, oral drugs approved and/or marketed since 1937 demonstrates that the median molecular weight of oral drugs has increased substantially over the past 60 years. Fewer than 5% of approved/marketed oral drugs have more than 4-H bond donors and just 2% have MW>500 and >3 H-bond donors.     

Neutral theory of molecular evolution

DNA sequence data are generally interpreted as favouring Kimura's neutral theory but not without dissent and often with a great deal of controversy with respect to molecular clocks, DNA polymorphism, adaptive evolution, and gene genealogy. Although the theory serves as a guiding principle, many issues concerning mutation, recombination, and selection remain unsettled. Of particular importance is the need for more knowledge about the function and structure of molecules.     

A thermodynamic theory of evolution

As a closed thermodynamic system subject to an essentially constant free energy gradient, the biosphere must evolve toward a stationary state of maximum structuring and minimum dissipation with respect to this applied gradient. Since biological evolution occurs opportunistically through chance and selection, rather than as a direct response to the free energy gradient, the conformance of this phase of evolution with thermodynamics requires that natural selection, and the particular adaptive strategies employed by species of organisms, be related to the principles of increasing structuring and decreasing dissipation. In this paper, some general features of this relationship are proposed.     

The evolution of fitness in life-history theory

Theory concerning the evolution of life history (the schedule of reproduction and survival) focuses on describing the life history which maximises fitness. Although there is an intuitive link between life history and fitness, there are in fact several measures of the 'black box' concept of fitness. There has been a debate in the bio-mathematical literature on the predictive difference between the two most commonly used measures; intrinsic rate of increase r and net reproductive ratio R0. Although both measures aim to describe fitness, models using one of the measures may predict the opposite of similar models using the other measure, which is clearly undesirable. Here, I review the evolution of these fitness measures over the last four decades, the predictive differences between these measures and the resulting shift of the fitness concept. I focus in particular on some recent developments, which have solved the dilemma of predictive differences between these fitness measures by explicitly acknowledging the game-theoretical nature of life-history evolution.     

Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution

We present here the hologenome theory of evolution, which considers the holobiont (the animal or plant with all of its associated microorganisms) as a unit of selection in evolution. The hologenome is defined as the sum of the genetic information of the host and its microbiota. The theory is based on four generalizations: (1) All animals and plants establish symbiotic relationships with microorganisms. (2) Symbiotic microorganisms are transmitted between generations. (3) The association between host and symbionts affects the fitness of the holobiont within its environment. (4) Variation in the hologenome can be brought about by changes in either the host or the microbiota genomes; under environmental stress, the symbiotic microbial community can change rapidly. These points taken together suggest that the genetic wealth of diverse microbial symbionts can play an important role both in adaptation and in evolution of higher organisms. During periods of rapid changes in the environment, the diverse microbial symbiont community can aid the holobiont in surviving, multiplying and buying the time necessary for the host genome to evolve. The distinguishing feature of the hologenome theory is that it considers all of the diverse microbiota associated with the animal or the plant as part of the evolving holobiont. Thus, the hologenome theory fits within the framework of the 'superorganism' proposed by Wilson and Sober.     

Game theory and the evolution of behaviour.

How far can game theory account for the evolution of contest behaviour in animals? The first qualitative prediction of the theory was that symmetric contests in which escalation is expensive should lead to mixed strategies. As yet it is hard to say how far this is borne out, because of the difficulty of distinguishing a 'mixed evolutionarily stable strategy' maintained by frequency-dependent selection from a 'pure conditional strategy'; the distinction is discussed in relation to several field studies. The second prediction was that if a contest is asymmetric (e.g. in ownership) then the asymmetry will be used as a conventional cue to settle it. This prediction has been well supported by observation. A third important issue is whether or not information about intentions is exchanged during contests. The significance of 'assessment' strategies is discussed.