Genetic Constraints on Protein Evolution

ABSTRACT

Evolution requires the generation and optimization of new traits (“adaptation”) and involves the selection of mutations that improve cellular function. These mutations were assumed to arise by selection of neutral mutations present at all times in the population. Here we review recent evidence that indicates that deleterious mutations are more frequent in the population than previously recognized and that these mutations play a significant role in protein evolution through continuous positive selection. Positively selected mutations include adaptive mutations, i.e. mutations that directly affect enzymatic function, and compensatory mutations, which suppress the pleiotropic effects of adaptive mutations. Compensatory mutations are by far the most frequent of the two and would allow potentially adaptive but deleterious mutations to persist long enough in the population to be positively selected during episodes of adaptation. Compensatory mutations are, by definition, context-dependent and thus constrain the paths available for evolution. This provides a mechanistic basis for the examples of highly constrained evolutionary landscapes and parallel evolution reported in natural and experimental populations. The present review article describes these recent advances in the field of protein evolution and discusses their implications for understanding the genetic basis of disease and for protein engineering in vitro.     

Effects of the [PSI+] prion on rates of adaptation in yeast

The [PSI(+)] prion in yeast has been shown to improve short-term growth in some environments, but its effects on rates of adaptation have not been assessed before now. We adapted three yeast genotypes to three novel environments in the presence and the absence of the prion. There were significant differences in adaptation rates between lines with different combinations of genotype, environment, and prion status. We saw no consistent effect, however, of the prion on the rate of adaptation to new environments. A major factor affecting the rate of adaptation was initial fitness in the new environment: lines with low initial fitness evolved faster than lines with high initial fitness.     

A genetic background with low mutational robustness is associated with increased adaptability to a novel host in an RNA virus

Although mutational robustness is central to many evolutionary processes, its relationship to evolvability remains poorly understood and has been very rarely tested experimentally. Here, we measure the evolvability of Vesicular stomatitis virus in two genetic backgrounds with different levels of mutational robustness. We passaged the viruses into a novel cell type to model a host‐jump episode, quantified changes in infectivity and fitness in the new host, evaluated the cost of adaptation in the original host and analyzed the genetic basis of this adaptation. Lineages evolved from the less robust genetic background demonstrated increased adaptability, paid similar costs of adaptation to the new host and fixed approximately the same number of mutations as their more robust counterparts. Theory predicts that robustness can promote evolvability only in systems where large sets of genotypes are connected by effectively neutral mutations. We argue that this condition might not be fulfilled generally in RNA viruses.     

microRNA分子表达与调控研究的最新进展

microRNA(miRNA)是一类分子长度为19~24nt的微小RNA,通常在转录后水平调控靶基因的降解或抑制翻译。miRNA分子在进化上高度保守,已经发现越来越多的miRNA分子参与真核生物的生长发育、生理活性、细胞增殖、组织分化、细胞凋亡、复杂疾病调控等功能。通过介绍miRNA的起源、合成、修饰、细胞表达特点,以及对真核细胞调控等的最新进展与研究方法,阐述miRNA在基因表达调节中的重要地位及应用前景。     

Heritability,covariation and natural selection on 24 traits of common evening primrose (Oenothera biennis) from a field experiment

This study explored genetic variation and co‐variation in multiple functional plant traits. Our goal was to characterize selection, heritabilities and genetic correlations among different types of traits to gain insight into the evolutionary ecology of plant populations and their interactions with insect herbivores. In a field experiment, we detected significant heritable variation for each of 24 traits of Oenothera biennis and extensive genetic covariance among traits. Traits with diverse functions formed several distinct groups that exhibited positive genetic covariation with each other. Genetic variation in life‐history traits and secondary chemistry together explained a large proportion of variation in herbivory (r² = 0.73). At the same time, selection acted on lifetime biomass, life‐history traits and two secondary compounds of O. biennis, explaining over 95% of the variation in relative fitness among genotypes. The combination of genetic covariances and directional selection acting on multiple traits suggests that adaptive evolution of particular traits is constrained, and that correlated evolution of groups of traits will occur, which is expected to drive the evolution of increased herbivore susceptibility. As a whole, our study indicates that an examination of genetic variation and covariation among many different types of traits can provide greater insight into the evolutionary ecology of plant populations and plant–herbivore interactions.     

Expression of Tyrosinase Gene in Transgenic Albino Mice: The Heritable Patterned Coat Colors

To elucidate the regulatory mechanism for tyrosinase gene expression in vivo, we microinjected a mouse tyrosinase minigene, mg-Qrs-J, into the fertilized eggs of BALB/c albino mice. As a result, we obtained six pigmented founder mice that exhibited non-standard coat color variations as well as the wild-type phenotype. These founder mice were subsequently crossed with BALB/c albino mice to establish the transgenic lines. As a consequence, two primary lines and five sublines have been obtained from four of the six founder mice. We found that not only uniformly pigmented phenotypes but also patterned phenotypes were inherited by their descendants. The possible underlying mechanism of the patterned phenotypes is discussed.