Outsourcing of energetically costly amino acids at the origin of animals

Kasalo, Niko; Domazet-Lošo, Mirjana; Domazet-Lošo, Tomislav (2026) Outsourcing of energetically costly amino acids at the origin of animals. Nature Communications, 17 (1). ISSN 2041-1723

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Abstract

Animals are generally capable of synthesizing eleven amino acids, while the remaining nine—often referred to as essential—must be acquired through diet. This metabolic trait profoundly shapes animal ecology and evolutionary trajectories, and recent phylogenomic studies indicate that it arose from gene losses at the root of the animal tree. However, it remains unclear which selective forces, if any, directed this far-reaching metabolic simplification. 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 the animal lifestyle. Using a probabilistic selection test, we find support for the hypothesis that energy-related selection, counterbalanced by pleiotropic effects, favored the outsourcing of essential amino acid production under well-oxygenated and nutrient-rich conditions. Remarkably, we also find that extant animals use expensive amino acids more frequently than their closest unicellular relatives, suggesting that constraints on their usage were relaxed once their synthesis was externalized, thereby enabling animal genes to evolve more freely across protein sequence space. In this light, we propose that the origin of animals was tightly linked to energy-related adaptations rather than to unpredictable stochastic events, as recently suggested.

Item Type:	Article
Uncontrolled Keywords:	Metazoa; essential amino acids; functional outsourcing; reductive evolution; energy management
Subjects:	NATURAL SCIENCES > Biology NATURAL SCIENCES > Biology > Genetics, Evolution and Phylogenetics TECHNICAL SCIENCES > Computing BIOTECHNICAL SCIENCES > Biotechnology > Bioinformatics
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Filostratigrafija nastanka i gubitka gena-PhyLoss Tomislav Domazet-Lošo IP-2016-06-5924 HRZZ DATACROSS - Napredne metode i tehnologije u znanosti o podatcima i kooperativnim sustavima (rezultat rada na projektu) Ivan Petrović; Tomislav Šmuc; PK.1.1.10.0007 EK Napredne metode i tehnologije u znanosti o podatcima i kooperativnim sustavima-DATACROSS Sven Lončarić; Ivan Petrović; Tomislav Šmuc; Andrej Jokić KK.01.1.1.01.0009 EK
Depositing User:	Ema Buhin Šaler
Date Deposited:	24 Feb 2026 12:56
URI:	http://fulir.irb.hr/id/eprint/11245
DOI:	10.1038/s41467-026-68724-6

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