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The 'polysemous' codon--a codon with multiple amino acid assignment caused by dual specificity of tRNA identity.

In some Candida species, the universal CUG leucine codon is translated as serine. However, in most cases, the serine tRNAs responsible for this non-universal decoding (tRNA(Ser)CAG) accept in vitro not only serine, but also, to some extent, leucine. Nucleotide replacement experiments indicated that m1G37 is critical for leucylation activity. This finding was supported by the fact that the tRNA(Ser)CAGs possessing the leucylation activity always have m1G37, whereas that of Candida cylindracea, which possesses no leucylation activity, has A37. Quantification of defined aminoacetylated tRNAs in cells demonstrated that 3% of the tRNA(Ser)CAGs possessing m1G37 were, in fact, charged with leucine in vivo. A genetic approach using an auxotroph mutant of C.maltosa possessing this type of tRNA(Ser)CAG also suggested that the URA3 gene inactivated due to the translation of CUG as serine was rescued by a slight incorporation of leucine into the polypeptide, which demonstrated that the tRNA charged with multiple amino acids could participate in the translation. These findings provide the first evidence that two distinct amino acids are assigned by a single codon, which occurs naturally in the translation process of certain Candida species. We term this novel type of codon a 'polysemous codon'.

Amino Acids↗

Nutritional and metabolic responses to arginine deficiency in carnivores.

The metabolic basis for the high dietary arginine requirement of the cat appears to be primarily the low activity of the enzyme pyrroline-5-carboxylate synthase (P5C synthase) in the intestinal mucosa. P5C synthase is required for de novo production of glutamyl-gamma-semialdehyde, the immediate precursor for the synthesis of ornithine from glutamate. The next enzyme in ornithine synthesis, ornithine amino-transferase, in the cat intestinal mucosa shows low activity, which provides an additional barrier to ornithine and citrulline formation. It is suggested that the low activities of these enzymes corroborate other evidence that indicates that the cat evolved as a strict carnivore. The dog has a requirement for arginine intermediate between the cat and the rat, which is consistent with the dog having an omnivorous diet during its evolution. It is suggested that during periods of fasting, depletion of urea cycle intermediates in the cat results in some conservation of nitrogen while maintaining urea cycle enzymes at a relatively high level. However, after ingestion of animal protein (and arginine) the urea cycle of cats is capable of rapidly responding to the ammonia load, which rises from the deamination of amino acids. By this method of regulation the cat can respond rapidly to short-term fluctuations in protein intake.

Aging↗

Stability of large segmental duplications in the yeast genome.

The high level of gene redundancy that characterizes eukaryotic genomes results in part from segmental duplications. Spontaneous duplications of large chromosomal segments have been experimentally demonstrated in yeast. However, the dynamics of inheritance of such structures and their eventual fixation in populations remain largely unsolved. We analyzed the stability of a vast panel of large segmental duplications in Saccharomyces cerevisiae (from 41 kb for the smallest to 268 kb for the largest). We monitored the stability of three different types of interchromosomal duplications as well as that of three intrachromosomal direct tandem duplications. In the absence of any selective advantage associated with the presence of the duplication, we show that a duplicated segment internally translocated within a natural chromosome is stably inherited both mitotically and meiotically. By contrast, large duplications carried by a supernumerary chromosome are highly unstable. Duplications translocated into subtelomeric regions are lost at variable rates depending on the location of the insertion sites. Direct tandem duplications are lost by unequal crossing over, both mitotically and meiotically, at a frequency proportional to their sizes. These results show that most of the duplicated structures present an intrinsic level of instability. However, translocation within another chromosome significantly stabilizes a duplicated segment, increasing its chance to get fixed in a population even in the absence of any immediate selective advantage conferred by the duplicated genes.

Fungal Proteins↗