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Biomedical subjects

C Alff-Steinberger

Publications and source records attributed to C Alff-Steinberger.

7 recordsLinked to original sources

A comparative study of mutations in Escherichia coli and Salmonella typhimurium shows that codon conservation is strongly correlated with codon usage.

Escherichia coli and Salmonella typhimurium are closely related species of enteric bacteria, having diverged from 120 to 160 million years ago, according to the estimate of Ochman & Wilson (1987. J. Mol. Evol.26, 74-86). In order to study base substitution mutations in the genomes of these bacteria, we have compared pairs of genes for the same product in the two species, and have selected a sample in which the protein length is the same in both E. coli and S. typhimurium. From the alignment of these gene pairs, we observe that frequently used codons are more conserved than infrequently used codons, i.e., the apparent mutation rate is higher for rare codons than for popular codons.

Codon↗

Codon usage in Homo sapiens: evidence for a coding pattern on the non-coding strand and evolutionary implications of dinucleotide discrimination.

This study reports the analysis of codon usage in 35 complete Homo sapiens genes. Both codon frequency and inter-codon interference exhibit patterns of evolutionary interest. There is a significant positive correlation between the frequency with which a given codon is used and the frequency with which its complement is used. Since the frequency of appearance of the complementary codon on the coding strand is equal to the frequency of appearance of the original codon on the non-coding strand, in the same phase, the non-coding strand is found to resemble the coding strand in triplet composition. The same effect has been observed in Escherichia coli. This preference for the use of certain complementary triplets as codons suggests that the evolution of the use of the genetic code depended to some extent upon the double-stranded nature of the coding material. In addition, the effect of discrimination against the use of two dinucleotides, CpG and UpA, is observed in codon usage and also in adjacent codon interference. Codons beginning with G, or A, are unlikely to be preceded by codons ending in C, or U, respectively. Consideration of codon assignment in the genetic code together with the observed CpG infrequency suggests that the evolution of the code may have been influenced by conditions in which the use of CpG dinucleotides was unfavorable. The infrequent use of UpA dinucleotides can be explained as the result of frameshift mutation during gene evolution.

Base Sequence↗

Evidence for a coding pattern on the non-coding strand of the E. coli genome.

Analysis of codon usage frequency for the combined coding sequences of 52 E. coli genes, taken from the European Molecular Biology Laboratory Nucleotide Sequence Data Library, Release 2, shows that there is a significant positive correlation between the frequency with which a given codon appears on the coding strand and the frequency with which it appears, in phase, on the non-coding strand.

Amino Acid Sequence↗

The genetic code and error transmission.

The amino acid substitutions resulting from single-base substitution in the natural genetic code have been compared with those resulting from single-base substitutions in computer-generated random codes. Considering the amino acid properties of molecular weight, polar requirement, number of dissociating groups, pK(1)', isoelectric point, and alpha-helix forming ability, it is concluded that, for the natural code, single-base substitution in the first position of the codon tends to result in the substitution of an amino acid more similar to the original amino acid than would be expected from a random code. In the natural code, the second position of the codon plays the largest role in determining the properties of the amino acid.

Amino Acid Sequence↗

Analysis of a copy number mutant of plasmid pSC101: co-maintenance of wild type and mutant plasmids.

We have isolated a high copy number mutant of plasmid pSC101 which is maintained at a level 4 times higher than that of the wild type. The mutation is a single base change that maps in codon 93 of the initiation protein RepA. We find that the mutation relaxes the autoregulation of the protein but increases its affinity for the repeated sequences in the origin. The wild type and the mutant repA genes are co-dominant and the mutated protein acts in trans even in the presence of the wild type protein. Co-maintenance of the two types of plasmids results in an intermediate copy number. Computer simulation indicates that simple models can explain the behaviour of the two plasmids.

Bacterial Proteins↗