Cytoplasmic methionyl tRNA synthetase (MetRS) is one of more than 20 cytoplasmic aminoacyl tRNA synthetase enzymes (ARS). This family of enzymes catalyzes a process fundamental for protein translation. Using a combination of genetic mapping, oligonucleotide array comparative genomic hybridization, and phenotypic correlation, we show that mutations in the essential gene,
let-65, reside within the predicted Caenorhabditis elegans homologue of MetRS, which we have named
mars-1. We demonstrate that the lethality associated with alleles of
let-65 is fully rescued by a transgenic array that spans the
mars-1 genomic region. Furthermore, sequence analysis reveals that six
let-65 alleles lead to the alteration of highly conserved amino acids.