Five hundred million years of hunger: how animals evolved to survive essential amino acid scarcity.

Proteins are the machinery for the processes of life. Each protein is made up of a defined combination of 20 building blocks, the amino acids. The animal kingdom is distinguished from most other forms of life by a half-billion-year-old choice to relinquish the synthesis of 9 of the 20 amino acids and instead rely on their dietary acquisition for protein synthesis. From that point onwards, animals entered into a permanent and obligatory hunt for these 'essential amino Acids' (EAAs). This perspective states that this seemingly destructive event was, in fact, foundational for the animal kingdom. Hypotheses for its origins are discussed, including a newly observed bias in EAA codon nucleotide composition that may help economise their use in proteins during scarcity. Tight restrictions on the inclusion of EAAs in protein sequences would be expected, but a minority of proteins with extreme EAA compositions are found. It is hypothesised that such proteins act as sentinels of EAA shortage in the diet, prompting beneficial responses from the organism. The control of hunger behaviours and reproductive timing are two processes in which EAA-rich proteins may be important. The leptin pathway of hunger behaviour regulation and reproductive development, traditionally associated with bodily lipid homeostasis, may be sensitive to EAA levels through this sequence-based mechanism. EAAs appear to have been a strong force in animal evolution. The biology emerging from their patterns of use in our proteins provides a direct link between nutritional state and specific biological processes - a coherent route to better dietary interventions in the future.