The Caenorhabditis elegans gene unc-22 encodes a very large muscle protein, called twitchin, which consists of a protein kinase domain and several copies of two short motifs. The sequence of twitchin has unexpected similarities to the sequences of proteins of the immunoglobulin superfamily, cell adhesion molecules and vertebrate muscle proteins, including myosin light-chain kinase. These homologies, together with results from earlier genetic and molecular analyses, indicate that twitchin is involved in a novel mechanism of myosin regulation.

We 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 oftotal 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 suggests that the mitochondrial DNA genes are highly prone to deleterious mutations.The ADP/ATP translocator, or adenine nucleotide translocator (ANT), is the most abundant mitochondrial protein (1). In its functional state it forms a dimer consisting of two identical 30-kDa subunits embedded asymmetrically in the inner mitochondrial membrane (2). The dimer forms a gated pore through which ADP is moved across the inner membrane into the mitochondrial matrix and ATP is moved from the matrix into the cytoplasm (2).Mitochondrial energy production varies greatly in importance between human tissues (3). Because the ANT determines the rate of ADP/ATP flux between the mitochondrion and the cytosol, the ANT would be a logical site for regulating cellular dependence on oxidative energy metabolism. Such regulation could be accomplished by producing varying amounts of the ANT or by elaborating tissue-specific ANT isoforms with different kinetic properties. Although Neurospora crassa has only one ANT gene (4), antigenic and electrophoretic mobility differences among bovine heart, kidney, and liver ANTs (5, 6) suggest that mammals may have multiple ANT genes that are expressed in a tissuespecific manner. Tissue-specific expression of functionally similar genes encoding proteins involved in oxidative phosphorylation (Ox/Phos) has been reported for the bovine ATP synthase proteolipid (7).The ANT and most other Ox/Phos genes are encoded in the nucleus, but 13 essential Ox/Phos polypeptides are encoded in the maternally inh...

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A 2.76 kb segment of the 12 kb divergent region of the Leishmania tarentolae kinetoplast maxicircle DNA consists almost entirely of repeated sequences. The repeats can be grouped into six families, some of which are present throughout the remainder of the divergent region. The repeats are oriented in a head-to-tail fashion with the three simplest repeats clustered into large arrays. A 47 bp palindrome and two copies of a "supercluster" of three different types of repeats are also present in the sequenced region. A sequence change in the divergent region is described for a clonal strain of L. tarentolae which was passaged continuously for several years. The repetitive sequences found in the divergent region appear to be appropriate substrates for the presumed deletion/insertion/recombination events occurring in this rapidly evolving portion of the maxicircle.

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