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The changes in codon adaptation in orthologous gene families can systematically predict function of many genes by employing machine learning to rule out confounding variables. We have experimentally validated novel roles in adaptation to environmental stressors (oxygen, heat, salinity) for tens of E. coli genes.

Comparative analyses of genomes, from bacteria across fungi to humans and human tumors have revealed many links between genes' biological roles and the accrual of synonymous mutations. The evolutionary trace of codon bias patterns across homologous genes may be examined to learn about a gene’s relevance to various phenotypes, or, more generally, its function in the cell.