Arginine limitation drives a directed codon-dependent DNA sequence evolution response in colorectal cancer cells Journal Article
| Authors: | Hsu, D. J.; Gao, J.; Yamaguchi, N.; Pinzaru, A.; Wu, Q.; Mandayam, N.; Liberti, M.; Heissel, S.; Alwaseem, H.; Tavazoie, S.; Tavazoie, S. F. |
| Article Title: | Arginine limitation drives a directed codon-dependent DNA sequence evolution response in colorectal cancer cells |
| Abstract: | Utilization of specific codons varies between organisms. Cancer represents a model for understanding DNA sequence evolution and could reveal causal factors underlying codon evolution. We found that across human cancer, arginine codons are frequently mutated to other codons. Moreover, arginine limitation—a feature of tumor microenvironments—is sufficient to induce arginine codon–switching mutations in human colon cancer cells. Such DNA codon switching events encode mutant proteins with arginine residue substitutions. Mechanistically, arginine limitation caused rapid reduction of arginine transfer RNAs and the stalling of ribosomes over arginine codons. Such selective pressure against arginine codon translation induced an adaptive proteomic shift toward low-arginine codon–containing genes, including specific amino acid transporters, and caused mutational evolution away from arginine codons—reducing translational bottlenecks that occurred during arginine starvation. Thus, environmental availability of a specific amino acid can influence DNA sequence evolution away from its cognate codons and generate altered proteins. Copyright © 2023 The Authors, some rights reserved. |
| Keywords: | genetics; proteins; metabolism; proteomics; colorectal neoplasms; dna; protein synthesis; colorectal tumor; nucleotide sequence; escherichia coli; protein biosynthesis; base sequence; mutant proteins; codon; diseases; cancer cells; arginine; dna sequences; human cancer; cells; tumor microenvironment; colorectal cancer cell; tumor microenvironments; humans; human; amino acid transporter; selective pressure; rapid reduction; arginine residue; human colon cancer cells |
| Journal Title: | Science Advances |
| Volume: | 9 |
| Issue: | 1 |
| ISSN: | 2375-2548 |
| Publisher: | Amer Assoc Advancement Science |
| Date Published: | 2023-01-04 |
| Start Page: | eade9120 |
| Language: | English |
| DOI: | 10.1126/sciadv.ade9120 |
| PUBMED: | 36608131 |
| PROVIDER: | scopus |
| PMCID: | PMC9821863 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2023 -- Source: Scopus |
