Human genome contains four genes homologous to transforming genes of Harvey and Kirsten murine sarcoma viruses.

Abstract

Harvey and Kirsten murine sarcoma viruses each encode a structurally and functionally related 21-kilodalton protein (p21), which is the transforming protein of each virus. Using probes from the 0.9-kilobase (kb) p21-coding region of each virus (called v-Ha-ras and v-Ki-ras, respectively), the sequences that hybridize to these probes were molecularly cloned from normal human genomic DNA. Four evolutionarily divergent restriction endonuclease fragments were isolated. Two hybridized preferentially to v-Ha-ras and were designated human c-Ha-ras1 and c-Ha-ras2; 2 hybridized preferentially to v-Ki-ras and were called c-Ki-ras1 and c-Ki-ras2. Human c-Ha-ras1 contained 0.9 kb of sequence homologous with v-Ha-ras interspersed with 3 intervening sequences; this gene was closely related to a previously cloned rat c-Ha-ras gene that also contained intervening sequences. Human c-Ha-ras2 was more divergent from v-Ha-ras and also hybridized poorly to human c-Ha-ras1. One c-Ki-ras gene contained 0.9 kb homologous to v-Ki-ras and had 1 intervening sequence, the other contained only 0.3 kb homologous to v-Ki-ras. Human DNA contains several copies of the c-ras gene family and c-Ha-ras1 (with intervening sequences) was more highly conserved evolutionarily than was c-Ha-ras2.