A Network Model for the Correlation between Epistasis and Genomic Complexity

Rafael Sanjuán,Miguel R Nebot,Jean-Nicolas Volff

doi:10.1371/journal.pone.0002663

Abstract

The study of genetic interactions (epistasis) is central to the understanding of genome organization and evolution. A general correlation between epistasis and genomic complexity has been recently shown, such that in simpler genomes epistasis is antagonistic on average (mutational effects tend to cancel each other out), whereas a transition towards synergistic epistasis occurs in more complex genomes (mutational effects strengthen each other). Here, we use a simple network model to identify basic features explaining this correlation. We show that, in small networks with multifunctional nodes, lack of redundancy, and absence of alternative pathways, epistasis is antagonistic on average. In contrast, lack of multi-functionality, high connectivity, and redundancy favor synergistic epistasis. Moreover, we confirm the previous finding that epistasis is a covariate of mutational robustness: in less robust networks it tends to be antagonistic whereas in more robust networks it tends to be synergistic. We argue that network features associated with antagonistic epistasis are typically found in simple genomes, such as those of viruses and bacteria, whereas the features associated with synergistic epistasis are more extensively exploited by higher eukaryotes.

Highlights

A consequence of genetic interactions is that the combined effect of two or more mutations often deviates from what can be expected by looking at each individual mutation [1,2]
A general correlation between epistasis and genomic complexity has been recently shown [8]. This correlation is such that in simple genomes as those of viruses and probably, some bacteria, epistasis tends to be antagonistic, whereas there is no apparent deviation from multiplicativity in unicellular eukaryotes and a transition towards synergistic epistasis occurs in higher eukaryotes
Selection should favour the evolution of developmental and somatic processes that increase genetic robustness in small populations with long generation times, whereas in large, rapidly replicating populations, lack of robustness should be selected [31]. These considerations lead us to expect that higher eukaryotes should to be more robust to mutation than viruses or bacteria and, as long as the correlation between robustness and epistasis holds, these differences would translate into differences in epistasis

Summary

Introduction

A consequence of genetic interactions is that the combined effect of two or more mutations often deviates from what can be expected by looking at each individual mutation [1,2]. It is obvious that network parts interact and that epistasis must be widespread, the causes for systematic deviations towards one kind of epistasis or another are still poorly understood Such deviations should play a key role in many evolutionary processes, including the evolution and maintenance of sexual reproduction [3], diploidy [4], dominance [5], speciation [6], or the genetic deterioration of small populations [7]. A general correlation between epistasis and genomic complexity has been recently shown [8] This correlation is such that in simple genomes as those of viruses and probably, some bacteria, epistasis tends to be antagonistic, whereas there is no apparent deviation from multiplicativity in unicellular eukaryotes and a transition towards synergistic epistasis occurs in higher eukaryotes. Recent advances in the characterization of molecular networks and in network theory provide new avenues for exploring the basis of epistasis and its relationship to complexity [9,10,11]

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Conclusion