cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, and coevolution with mitochondrial DNA genes

Journal Article · Sun Nov 01 00:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.21.7580· OSTI ID:6771309

Neckelmann, N; Li, K; Wade, R P; Shuster, R; Wallace, D C

The authors have characterized a 1400-nucleotide cDNA for the human skeletal muscle ADP/ATP translocator. The deduced amino acid sequence is 94% homologous to the beef heart ADP/ATP translocator protein and contains only a single additional amino-terminal methionine. This implies that the human translocator lacks an amino-terminal targeting peptide, a conclusion substantiated by measuring the molecular weight of the protein synthesized in vitro. A 1400-nucleotide transcript encoding the skeletal muscle translocator was detected on blots of total RNA from human heart, kidney, skeletal muscle, and HeLa cells by hybridization with oligonucleotide probes homologous to the coding region and 3' noncoding region of the cDNA. However, the level of this mRNA varied substantially among tissues. Comparison of our skeletal muscle translocator sequence with that of a recently published human fibroblast translocator cognate revealed that the two proteins are 88% identical and diverged about 275 million years ago. Hence, tissues vary both in the level of expression of individual translocator genes and in differential expression of cognate translocator genes. Comparison of the base substitution rates of the ADP/ATP translocator and the oxidative phosphorylation genes encoded by mitochondrial DNA revealed that the mitochondrial DNA genes fix 10 times more synonymous substitutions and 12 times more replacement substitutions; yet, these nuclear and cytoplasmic respiration genes experience comparable evolutionary constraints. This suggest that the mitochondrial DNA genes are highly prone to deleterious mutations.

• Research Organization: Emory Univ. School of Medicine, Atlanta, GA (USA)
• OSTI ID: 6771309
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:21
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
PROTEINS
AMINO ACID SEQUENCE
BIOLOGICAL EVOLUTION
GENE REGULATION
RECOMBINANT DNA
DNA SEQUENCING
ATP
DNA
ELECTROPHORESIS
FIBROBLASTS
GENES
HYBRIDIZATION
MESSENGER-RNA
MUSCLES
OLIGONUCLEOTIDES
PHOSPHORUS 32
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ISOTOPES
LIGHT NUCLEI
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RNA
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
550201* - Biochemistry- Tracer Techniques