Evolution under canalization and the dual roles of microRNAs—A hypothesis

Abstract

Canalization refers to the process by which phenotypes are stabilized within species. Evolution by natural selection can proceed efficiently only when phenotypes are canalized. The existence and identity of canalizing genes have thus been an important, but controversial topic. Recent evidence has increasingly hinted that microRNAs may be involved in canalizing gene expression. Their paradoxical properties (e.g., strongly conserved but functionally dispensable) suggest unconventional regulatory roles. We synthesized published and unpublished results and hypothesize that miRNAs may have dual functions-in gene expression tuning and in expression buffering. In tuning, miRNAs modify the mean expression level of their targets, but in buffering they merely reduce the variance around a preset mean. In light of the constant emergence of new miRNAs, we further discuss the relative importance of these two functions in evolution.Living organisms process as much information and execute as many instructions as any high-power computers normally do. The difference is that living organisms carry out the tasks under extremely variable environments, whereas no computers are made to withstand even moderate fluctuations in voltage input. Living things must be able to dampen variable inputs (in nutrition, temperature, humidity, genetic background, etc.) to achieve the remarkable stability in the output (development, physiological responses, gene expression, etc.). This phenomenon is the essence of biological homeostasis.Darwin's The Origin of Species (Darwin 1859), on the other hand, is about evolutionary changes. On the surface, evolutionary changes and phenotypic stability may seem like antithetical concepts, but in the language of genetics they are really two sides of the same issue. Evolution by natural selection can proceed only when biological systems are reasonably stable. Imagine a system in which phenotypic manifestation is highly variable. In it natural selection cannot easily distinguish one genotype from another and would have low efficacy. The original nongenetic version of the Darwinian theory encountered many difficulties. One of them was the blending of genetic materials, potentially leading to the homogenization of phenotypes. The other resulted from the ignorance of the difference between genotype and phenotype and the puzzle over the existence of phenotypic variation. Fisher (1930) pointed out that, in Darwin's thinking, phenotypic variation should have been purged by natural selection-only the fittest should have remained.The relationship between evolution and biological homeostasis can best be expressed in quantitative genetic terms. Let V g and V e denote phenotypic variance due to genotypic and environmental effect, respectively. V g 3 e is the interactive term between gene and environment. The total phenotypic variance, V t , can be expressed as follows:For simplicity, we assume no dominance here, but the general principle is the same in more complex systems. Any mechanism of biological homeostasis should redu...

The evolution of evolvability in microRNA target sites in vertebrates

“…In addition to the measurement errors, the feedback loops and other systems motifs would often interfere with the miRNA-target interactions. Previous studies (Karres et al 2007;Wu et al 2009;Tang et al 2010) …”

“…MicroRNAs (miRNAs) are a group of endogenous small RNAs (;22 nt) that play an important role in the gene regulatory system (He and Hannon 2004;Stark et al 2005;Bushati and Cohen 2007;Flynt and Lai 2008;Wu et al 2009;Aqeilan et al 2010). A typical miRNA binds to the complementary sequences on target mRNAs, resulting in translational repression or target degradation (Bartel 2009).…”

MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells

“…In fact, 30% of the transcriptome is regulated by miRNAs, and 25% of miRNA recognition elements between human and mouse is highly conserved (16,17,37). We used prediction algorithm in TargetScan to mine the 3ЈUTR of IGF-1R mRNA for the miRNA recognition element.…”

Robustness of the hypoxic response: Another job for miRNAs?

“…Genome-scale analyses revealed that feedback and feedforward loops that contain miRNAs are also recurrent network motifs in large gene networks (Tsang et al, 2007;Martinez et al, 2008;Re et al, 2009), so that miRNAs can provide biological robustness by participating in these loops (Hornstein and Shomron, 2006;Wu et al, 2009a;Herranz and Cohen, 2010;Osella et al, 2011;Pelaez and Carthew, 2012). miRNAs are small (approximately 22 nucleotides) noncoding single-stranded RNAs that regulate gene expression post-transcriptionally.…”

“…Feedforward loops can confer robustness through different mechanisms. They can buffer the impact of noise on target gene expression, contributing to enhance the robustness of the network Hornstein and Shomron, 2006;Wu et al, 2009a;Osella et al, 2011). In an incoherent feedforward loop, fluctuations of the upstream factor are uncoupled from the final output of the target gene, because the intermediate component of the indirect path of the loop will compensate changes in the input signal (Ebert and Sharp, 2012).…”