Non-adaptive complexity and biochemical function

Intricate biochemical structures are usually thought to be useful, because natural selection preserves them from degradation by a constant hail of destructive mutations. Biochemists therefore often deliberately disrupt them to understand how complexity improves protein function or fitness. However, evolutionary theory suggests that even useless complexity that never improved fitness can become completely essential if a simple set of evolutionary conditions is fulfilled. We review evidence that stable protein complexes, protein-chaperone interactions, and complexes consisting of several paralogs all fulfill these conditions. This makes reverse genetics or destructive mutagenesis unsuitable for assigning functions to these kinds of complexity. Instead, we advocate that incorporating evolutionary approaches into biochemistry overcomes this difficulty and allows us to distinguish useless from useful biochemical complexity.