Redundancy, antiredundancy, and the robustness of genomes

TLDR

Redundancy, the presence of functionally overlapping genes or pathways, is common in organisms with low mutation rates and small populations, whereas high mutation rates and large populations, or rapidly dividing multicellular cells, exhibit antiredundancy, a hypersensitivity to mutation. The study analyzes the evolutionary dynamics of redundancy and antiredundancy. The authors model these dynamics to assess how populations evolve redundancy or antiredundancy. Large populations evolve antiredundant mechanisms that enhance genome robustness, while small populations evolve redundancy to increase survival probability; antiredundancy is also crucial for developmental robustness and may impact cancer, mitochondrial disease, and viral infection.

Abstract

Genetic mutations that lead to undetectable or minimal changes in phenotypes are said to reveal redundant functions. Redundancy is common among phenotypes of higher organisms that experience low mutation rates and small population sizes. Redundancy is less common among organisms with high mutation rates and large populations, or among the rapidly dividing cells of multicellular organisms. In these cases, one even observes the opposite tendency: a hypersensitivity to mutation, which we refer to as antiredundancy. In this paper we analyze the evolutionary dynamics of redundancy and antiredundancy. Assuming a cost of redundancy, we find that large populations will evolve antiredundant mechanisms for removing mutants and thereby bolster the robustness of wild-type genomes; whereas small populations will evolve redundancy to ensure that all individuals have a high chance of survival. We propose that antiredundancy is as important for developmental robustness as redundancy, and is an essential mechanism for ensuring tissue-level stability in complex multicellular organisms. We suggest that antiredundancy deserves greater attention in relation to cancer, mitochondrial disease, and virus infection.