PubMed HealthSearch

Biomedical subjects

R Grantham

Publications and source records attributed to R Grantham.

11 recordsLinked to original sources

Avoidance of base runs in switch regions of immune-system genes.

Mouse immunoglobulin (Ig) switch-region sequences are anti-"runny"; that is, they have a smaller amount of their total bases in homonucleotide tracts ("runs") than would be expected if each nucleotide in the sequence were a random selection from a pool of the composition of the region. The switch sequences involve the first intron of rearranged Ig heavy-chain genes; this intron differs strikingly from the succeeding ones, which are "runny" (have more bases than expected in runs). Switch regions are the only category of sequences so far found to be antirunny by statistical test. This sequence characteristic is related to the presence in switch sequences of repeating heteronucleotides. We suggest that the resulting base dispersion and increased complexity favor more specific interactions between sequences, which may be advantageous in recombinational processes such as switching and translocation.

Animals

Codon frequencies in 119 individual genes confirm consistent choices of degenerate bases according to genome type.

The poor printing of our previous Figure 2 (1) is corrected. Codon usage in mRNA sequences just published is also given. A new correspondence analysis is done, based on simultaneous comparison in all mRNA of use of the 61 codons. This analysis reinforces our claim that most genes in a genome, or genome type, have the same coding strategy; that is, they show similar choices among synonymous codons, or among degenerate bases (2). Like analysis on frequency variation in the amino acids coded reveals an entirely different pattern.

Animals

Codon catalog usage and the genome hypothesis.

Frequencies for each of the 61 amino acid codons have been determined in every published mRNA sequence of 50 or more codons. The frequencies are shown for each kind of genome and for each individual gene. A surprising consistency of choices exists among genes of the same or similar genomes. Thus each genome, or kind of genome, appears to possess a "system" for choosing between codons. Frameshift genes, however, have widely different choice strategies from normal genes. Our work indicates that the main factors distinguishing between mRNA sequences relate to choices among degenerate bases. These systematic third base choices can therefore be used to establish a new kind of genetic distance, which reflects differences in coding strategy. The choice patterns we find seem compatible with the idea that the genome and not the individual gene is the unit of selection. Each gene in a genome tends to conform to its species' usage of the codon catalog; this is our genome hypothesis.

Animals

[Composition and variability of bases in degenerate and non-degenerate positions in codons of various types of mRNA].

Codon base frequencies have been studied in all published mRNA sequences of more than 50 codons. Bases are not "random" in any codon position. Variability in degenerate position III is of the same order as in the other two positions (non-degenerate). The base distribution in each codon position is significantly different from that in each other position. Position I has the most distinctive make up. Correlations demonstrate that in this ensemble of 1,265 codons positions I and II have the same type of composition as in the decoded mRNA for the average protein.

Base Sequence

Amino acid difference formula to help explain protein evolution.

A formula for diference between amino acids combines properties that correlate best with protein residue substitution frequencies: composition, polarity, and molecular volume. Substitution frequencies agree much better with overall chemical difference between exchanging residues than with minimum base changes between their codons. Correlation coefficients show that fixation of mutations between dissimilar amino acids is generally rare.

Amino Acids