Linkage of theleuS, emtB, andchr genes on chromosome 5 in humans and expression of human genes encoding protein synthetic components in human-Chinese hamster hybrids

Abstract

We isolated interspecific hybrids between normal human leukocytes and a Chinese hamster ovary cell line that has mutations in three genes, leuS, emtB,and chr,all of which are linked to chromosome 2. The conditionally lethal mutation in the leuSgene in this cell line affects leucyl-tRNA synthetase and renders the cell line nonviable at 39°C. The mutation in the emtBlocus alters ribosomal protein S14 and results in the cell line being resistant to the protein synthesis inhibitor, emetine, while the mutation in the chrlocus renders the cells resistant to sodium chromate. The interspecific hybrids were selected at 39°C so that they were required to retain and express the human leuSgene. Ten out of ten such heat-resistant hybrids also expressed the human emtBand chrgenes. Segregants selected as having lost the human emtBgene simultaneously lost the human chrand leuSgenes as well. The linkage relationship between these three genes has thus been conserved during the evolution of the human and Chinese hamster genomes. All three genes were localized to human chromosome 5. Furthermore, our results indicate that the ribosomal protein product of the human emtBgene is incorporated into functional ribosomes in place of the corresponding Chinese hamster protein, raising several interesting questions concerning the coordinate regulation of genes encoding ribosomal proteins in mammalian cells.