Massive outsourcing of energetically costly amino acids at the origin of animals

Animals are generally capable of synthesizing eleven amino acids, while the remaining nine, often referred to as essential, must be acquired through diet. This characteristic profoundly impacts animals by defining their ecological lifestyles and evolutionary trajectory. Recent phylogenomic studies reveal that this phenotype results from gene losses that occurred at the root of the animal tree. However, it remains unclear which selective forces, if any, directed this far-reaching metabolic simplification event. Here, we show that essential amino acids are energetically far more expensive to synthesize than non-essential ones, particularly under high respiratory conditions—a hallmark of animal lifestyle. By applying permutation tests, we found that these difference in energy costs, counteracted by pleiotropy, created a selective pressure which led to the outsourcing of essential amino acids. Remarkably, we also found that extant animals use expensive amino acids more frequently compared to their closest unicellular relatives. This shows that animals significantly removed constraints on the usage of essential amino acids under high respiratory conditions by externalizing their production. Together, this implies that stabilizing selection underpinned by energy management drove this metabolic outsourcing in nutrient rich environments, thereby allowing animal genes to evolve more freely through protein sequence space. In this context, we propose that the origin of animals is tightly linked to energy-related adaptations rather than to unpredictable stochastic events, as recently suggested.