Richard Grantham

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.

Codon catalog usage is a genome strategy modulated for gene expressivity

The nucleic acid sequence bank now contains 161 mRNAs, 43 new genes are added. One sequence, that of B. mori fibroin, is dropped due to uncertainty on the starting point for translation. Frequencies of all codons are given for each gene added and for each genome type in the total bank. A new series of correspondence analyses on codon use is presented, substantiating the genome hypothesis. Internal regulation of mRNA expression by different third base choices between quartet and duet codons is proposed for bacterial genes.

Polypeptide elongation and tRNA cycling in Escherichia coli: A dynamic approach

Understanding the functioning of the genetic code in the prokaryote system is progressing rapidly. We present here a synthesis of the dynamic aspects of Escherichia coli protein biosynthesis, based on quantitative data to the extent possible. Previous work along this line was undertaken when few experimental data were available [l-3]. More recent authors have focused on incorporation errors [4-81 or the possible influence of mRNA secondary structure on ribosome movement [9,10]. Although quantities of most of the active molecules have now been estimated, measurement of the duration of many steps in this complex process is difficult. This is one justification for our theoretical approach. We have done Brownian motion computer simulations to determine the duration of the ribosomal A-site searches by tRNAs. Our main result is a dynamic interpretation of the observed relative quantities of ribosomes and the molecules which ‘feed’ them. We find that these quantities are optimized to maintain maximum polypeptide elongation rate at various cell growth rates. We also calculate the mean duration of several steps in the tRNA cycle.

Nucleic acid sequence similarities: ‘Poly(A) tendency’

The origin and evolution of viruses is coming under stronger attack, thanks to the increasing availability of gene and genome sequences. However, the methodology is still narrow, being mainly based on alignment of sequences. In this paper I continue the effort to develop indexes for characterizing nucleic acid sequences and establishing relatedness among them [l]. As previously shown, the DNA sequences of papova virus SV40 and the untranslated zone following the chicken ovalbumin gene are similar in having very low frequencies for the dlnucleotide CG [I]. An additional likeness is here described in ‘poly(A) tendency’. A sequence with poly(A) tendency has an elevated frequency for purely adenine (A) containing o~gonucleotides of 4 or more bases in length. Two sample sequences high in runs of A are compared to all pub~~ed mRNA sequences [2] and to a large number of untranslated sequences. AAAA is the most frequent of the 256 possible tetranucleotides in the 637 untranslated bases 3’ to the chicken ovalbumin codons [3] (6370~3’) and in 4 papova virus genes, as revealed below. Although I find poly(A) tendency throughout the SV40 and BKV genomes [4-71, the VP1 gene is most like 6370~3’ in this respect. The maximum tendency in SV40 (the two papova genomes are very similar in poly(A) tendency, see below) is reached in the first half of VP1 .