Neutral network

A neutral network is a set of genes all related by point mutations that have equivalent function or fitness. Each node represents a gene sequence and each line represents the mutation connecting two sequences. Neutral networks can be thought of as high, flat plateaus in a fitness landscape. During neutral evolution, genes can randomly move through neutral networks and traverse regions of sequence space which may have consequences for robustness and evolvability.

Neutral networks exist in fitness landscapes since proteins are robust to mutations. This leads to extended networks of genes of equivalent function, linked by neutral mutations. Proteins are resistant to mutations because many sequences can fold into highly similar structural folds. A protein adopts a limited ensemble of native conformations because those conformers have lower energy than unfolded and mis-folded states (ΔΔG of folding). This is achieved by a distributed, internal network of cooperative interactions (hydrophobic, polar and covalent). Protein structural robustness results from few single mutations being sufficiently disruptive to compromise function. Proteins have also evolved to avoid aggregation as partially folded proteins can combine to form large, repeating, insoluble protein fibrils and masses. There is evidence that proteins show negative design features to reduce the exposure of aggregation-prone beta-sheet motifs in their structures. Additionally, there is some evidence that the genetic code itself may be optimised such that most point mutations lead to similar amino acids (conservative). Together these factors create a distribution of fitness effects of mutations that contains a high proportion of neutral and nearly-neutral mutations.

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