The Effects of Stabilizing and Directional Selection on Phenotypic and Genotypic Variation in a Population of RNA Enzymes

Abstract

The distribution of variation in a quantitative trait and its underlying distribution of genotypic diversity can both be shaped by stabilizing and directional selection. Understanding either distribution is important, because it determines a population's response to natural selection. Unfortunately, existing theory makes conflicting predictions about how selection shapes these distributions, and very little pertinent experimental evidence exists. Here we study a simple genetic system, an evolving RNA enzyme (ribozyme) in which a combination of high throughput genotyping and measurement of a biochemical phenotype allow us to address this question. We show that directional selection, compared to stabilizing selection, increases the genotypic diversity of an evolving ribozyme population. In contrast, it leaves the variance in the phenotypic trait unchanged. AbstractThe distribution of variation in a quantitative trait and its underlying distribution of genotypic diversity can both be shaped by stabilizing and directional selection. Understanding either distribution is important, because it determines a population's response to natural selection. Unfortunately, existing theory makes conflicting predictions about how selection shapes these distributions, and very little pertinent experimental evidence exists. Here we study a simple genetic system, an evolving RNA enzyme (ribozyme) in which a combination of high throughput genotyping and measurement of a biochemical phenotype allow us to address this question. We show that directional selection, compared to stabilizing selection, increases the genotypic diversity of an evolving ribozyme population. In contrast, it leaves the variance in the phenotypic trait unchanged.3

Limits of Neutral Drift: Lessons From the In Vitro Evolution of Two Ribozymes

“…Such tolerance to sequence variation has been proposed as a correlate of evolvability in changing environments (Wagner 2008; Wagner 2013).Neutral drift has been used to create libraries of functional protein variants that are especially capable of subsequent adaptive evolution (Bershtein et al 2008; Gupta and Tawfik 2008). Another recent study examinedevolving populations of the Azoarcus group I ribozyme that first were subject to stabilizing selection with the opportunity for neutral mutations, followed by directional selectionthat resulted in adaptation to an alternativesubstrate (Hayden et al 2011; Hayden et al 2014). Conditionally neutral, cryptic variation that accumulated in the first phase was found to facilitate adaptation in the second phase.…”

Elucidating the molecular architecture of adaptation via evolve and resequence experiments

“…NGS allows testing the selected population in earlier rounds and provides a much more complete picture of the final array of winning genotypes 44 . In fact, direct experimental measurement of the fitness landscapes of RNA ligase 15 , kinase 45 , Diels-Alderase 46 , and self-splicing ribozymes 47 are obtained at much higher resolution than ever before. Combined with microfluidic analytical platforms, NGS can be directly coupled to activity measurement, revealing the fitness landscape of a functional RNA 48,49 .…”

Does Long-Term Selection for Development Time Result in Canalization: A Test UsingDrosophila melanogaster

“…Overall, then, our results underscore that whether or not canalization results from directional selection may often depend on the trait in question, the environmental factor under study, the definition of canalization, and specific details of the ecology and physiology of the populations studied. Some other recent findings also suggest that directional and disruptive selection may not always lead to decanalization as predicted by theory (Hansen et al, 2006;Hayden et al, 2014 ). Some caution is, therefore, in order when drawing generalized conclusions about the relationship between different forms of selection and canalization from a hypothetical perspective:such relationships be need to be explored on a case-by-case basis and canalization, like evolution in general, may turn out to be 'local' (sensu Rose et al, 2005).…”

“…Besides, demonstration of canalizing effect of the chaperone protein Hsp90 in Drosophila (Rutherford and Lindquist, 1998) and Arabidopsis (Sangster et al, 2008) on a wide variety of morphological traits provided the first evidence of canalizing mechanisms at the molecular level. Recent literature shows an upsurge in interest on canalization in molecular biology as canalization is being investigated for suite of traits ranging from transcript abundance to gene regulatory networks to ribozyme diversity (Hayden et al 2014;Félix and Barkoulas, 2015). However, studies exploring canalization of complex life-history traits are rare.…”