Nucleotide sequence analysis of human c-myc locus, chicken homologue, and myelocytomatosis virus MC29 transforming gene reveals a highly conserved gene product.

We have determined the complete nucleotide sequence of human cellular c-myc, which is homologous to the transforming gene, v-myc, of myelocytomatosis virus MC29. Analysis of the genetic information and alignment with the known sequence of chicken c-myc and v-myc indicates: (i) An intervening sequence can be identified by consensus splice signals. The unique 5' sequence of c-myc and its junction with the v-myc region may be a canonical 3' splice acceptor. (ii) The c-myc locus can generate a mRNA whose termination signals are downstream from the translational termination signal. (iii) The three myc genes share the same reading frame, including translational termination signals. (iv) The homology is conserved only in the coding region. (v) Most changes at the nucleotide level result in no change in the amino acid. (vi) There are two distinct domains--the 5' unique domain, which is different from the viral, and the 3' coding domain, which contains amino acids coded by the two exons whose sequences have been determined here. In the latter domain, the amino acid variation between v-myc and chicken c-myc is less than 2%, whereas that between the chicken v-myc and the human is 27%, with the variation concentrated in the region that flanks the splicing points.