Arginine limitation causes a directed DNA sequence evolution response in colorectal cancer cells

• DOI: 10.1101/2023.01.02.521806
• Publication Date: 2023-01-02T21:45:17Z
• Authors: Dennis J. Hsu; Jenny Gao; Norihiro Yamaguchi; Alexandra Pinzaru; Nandan Mandayam; Maria Liberti; Søren Heissel; Hanan Alwaseem; Saeed Tavazoie; Sohail F. Tavazoie
• Keywords: 0301 basic medicine; 03 medical and health sciences; Article; 3. Good health

Abstract Utilization of specific codons varies significantly across organisms. Cancer represents a model for understanding DNA sequence evolution and could reveal causal factors underlying codon evolution. We found that human cancer, arginine are frequently mutated to other codons. Moreover, restriction—a feature tumor microenvironments—is sufficient induce codon-switching mutations in colon cancer cells. Such switching events encode mutant proteins with residue substitutions. Mechanistically, limitation caused rapid reduction transfer RNAs the stalling ribosomes over selective pressure against translation induced proteomic shift towards low containing genes, including amino acid transporters, mutational away from codons—reducing translational bottlenecks occurred during starvation. Thus, environmental availability can influence its cognate generate altered proteins.