Congruent evolution of genetic and environmental robustness in microRNA

TL;DR

This study investigates the evolution of genetic and environmental robustness in microRNA genes, revealing a correlation likely due to biophysical constraints and suggesting genetic robustness may be a byproduct of environmental robustness selection.

Contribution

The paper introduces a novel measure of environmental robustness and demonstrates its correlation with genetic robustness in miRNA, supporting the plastogenetic congruence theory.

Findings

Genetic robustness in miRNA is uncorrelated with traditional environmental robustness measures.

RNA folding biophysics induces a high correlation between genetic and environmental robustness.

Genetic robustness in miRNA likely arises as a byproduct of selection for environmental robustness.

Abstract

Genetic robustness, the preservation of an optimal phenotype in the face of mutations, is critical to the understanding of evolution as phenotypically expressed genetic variation is the fuel of natural selection. The origin of genetic robustness, whether it evolves directly by natural selection or it is a correlated byproduct of other phenotypic traits, is, however, unresolved. Examining microRNA (miRNA) genes of several eukaryotic species, Borenstein and Ruppin (Borenstein et al. 2006, PNAS 103: 6593), showed that the structure of miRNA precursor stem-loops exhibits significantly increased mutational robustness in comparison with a sample of random RNA sequences with the same stem-loop structure. The observed robustness was found to be uncorrelated with traditional measures of environmental robustness -- implying that miRNA sequences show evidence of the direct evolution of genetic robustness. These findings are surprising as theoretical results indicate that the direct evolution of robustness requires high mutation rates and/or large effective population sizes only found among RNA viruses, not multicellular eukaryotes. Introducing a novel measure of environmental robustness based on the equilibrium thermodynamic ensemble of secondary structures of the miRNA precursor sequences we demonstrate that the biophysics of RNA folding, induces a high level of correlation between genetic (mutational) and environmental (thermodynamic) robustness, as expected from the theory of plastogenetic congruence introduced by Ancel and Fontana (Ancel et al. 2000, J. Exp. Zool. 288: 242). In light of theoretical considerations we believe that this correlation strongly suggests that genetic robustness observed in miRNA sequences is the byproduct of selection for environmental robustness.