Detection of mutations: from Ames test to duplex sequencing

Mutation is a biological phenomenon observed in all life forms from viruses to humans. This inescapable process has fascinated scientists for nearly a century. Mutagenicity has become a concern since the 1940s following the discovery that chemicals can cause mutations, because of which the scientific community has ventured into finding effective methods of detecting harmful mutagens. The earlier studies in this field were carried out using organisms like Escherichia coli , Drosophila , and Neurospora . Later, the breakthrough development of an assay using bacteria allowed researchers to detect the abilities of chemical compounds or mixtures to induce DNA mutations. This assay came to be named as the Ames test after its developer Bruce Ames; since then, it has been widely adopted for mutagenicity testing. The introduction of Sanger sequencing technology enabled researchers to explore beyond phenotypic changes and uncover detailed information on DNA sequence changes and mutational spectra. With the advent of next-generation sequencing (NGS), it has become possible to expand mutation analysis to the larger genome without the need for phenotypic selection, particularly given the development of various error-corrected NGS (ecNGS) techniques. Duplex sequencing (DS) is a relatively new ecNGS technique that can detect mutations at low frequencies in isolated DNA. In this mini review, we briefly explore the genetics of the Ames test and shed light on DS as an emerging tool for detecting mutations.