Species extinction risk is shaped by proteome-level amino acid composition and selective codon usage

Patterns of species extinction are interpreted through ecological, climatic, or macroevolutionary pressures. Currently, we identify a previously unrecognized biochemical signature associated with extinction risk: the proteome-wide amino-acid composition and codon-usage profiles of organisms. Using a cross-kingdom dataset spanning animals, plants, and microorganisms, we evaluated how extinction status relates to global proteomic-trends and codon-preference. Taxa that are extinct or critically endangered display higher proportions of hydrophobic, bulky, and metabolically costly amino acids, whereas lineages that remain extant—including metabolically-efficient extremophiles—show enrichment for smaller, low-cost residues such as alanine and glycine. Across seven independent analytical approaches—compositional enrichment tests, multivariate analyses, conditional amino acid distributions, codon usage assessments, and extremophile–mesophile contrasts—we consistently detect a pattern linking proteomic economy to long-term evolutionary persistence. Codon-usage patterns further differentiate these groups: extinct taxa disproportionately employ rare, energetically expensive codons for bulky or costly amino acids, increasing translational load and reducing mutational tolerance, whereas extant and extremophilic species prefer high-frequency, energy-efficient codons that facilitate rapid and accurate translation. Additionally, Bayesian-analysis of logistic-regression predicted possible timeframe of extinction threat for several existing-species including higher mammals. Together, these findings suggest that proteome-level biochemical constraints contribute to lineage-stability by modulating metabolic-resilience, environmental-adaptability, and robustness to mutational-stress.