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R Holmquist

Publications and source records attributed to R Holmquist.

16 recordsLinked to original sources
PubMed1979

beta-Galactosidase and selective neutrality.

Three hypotheses to explain the amino acid composition of proteins are inconsistent (P congruent to 10(-9) with the experimental data for beta-galactosidase from Escherichia coli. The exceptional length of this protein, 1021 residues, permits rigorous tests of these hypotheses without complication from statistical artifacts. Either this protein is not at compositional equilibrium, which is unlikely from knowledge about other proteins, or the evolution of this protein and its coding gene have not been selectively neutral. However, the composition of approximately 60 percent of the molecule is consistent with either a selectively neutral or nonneutral evolutionary process.

Amino Acid Sequence↗
PubMed1979

Chromatography of a Triton extracted beef cardiac cytochrome C1 preparation on diethylaminoethyl cellulose.

During the chromatography of a Triton X-100 extracted preparation of the mitochondrial membrane proteins on diethylaminoethyl cellulose, we have observed two chromatographic fractions containing cytochrome c1. One elutes from diethylaminoethyl cellulose with aqueous buffers alone, and the other elutes with those buffers after the addition of the nonionic detergent Triton X-100. The two forms occur in equimolar ratios and each retains its original chromatographic character on rechromatography, with no conversion of one form into the other.

Animals↗
PubMed1978

Evaluation of compositional nonrandomness in proteins.

Cornish-Bowden and Marson have recently suggested that the finite sampling component of Q, a measure of nonrandomness in the amino acid composition of proteins, may have been underestimated because it was calculated on the basis of the genetic code table frequencies rather than on the basis of the average natural abundance with which the twenty amino acids actually occur in proteins. This underestimate would lead to an overestimate of Qc a measure of selective effects above and beyond those imposed by the average natural abundance of the amino acids. In this paper the finite sampling component of Q is quantitatively estimated on the basis of these natural abundances and found to reduce Qc from its previous average value of 24.3 to the lower value of 9.7, with the standard deviation of the population of Qc values being 12.5. Individual Qc values are given for 81 protein families of mean composition per 61 codons of Ala5.3Arg2.4Asn3.0Asp3.6Cys1.5Gln2.6Glu3.5Gly4.7His1.3Ile3.4Leu4.5Lys4.2Met1.0Phe2.3Pro2.3Ser4.2Thr3.6Trp0.8Tyr2.6Val4.2. The mean Qc value of 9.7 is notably small, and indicates that quantitatively minimal adjustments away from the average protein composition are necessary to maintain many different biological functions. This small value, however, is shown to differ significantly from the value of zero expected were the natural abundances of the amino acids the only selective constraint. These small deviations from the natural abundances are thus effectively selected for in the Darwinian sense.

Amino Acid Sequence↗
PubMed1978

A measure of the denseness of a phylogenetic network.

The concept of phylogenetic denseness bears critically on the accuracy of evolutionary pathways inferred from experimentally sequenced proteins isolated from extant species. In this paper I develop an objective measure, rho, of denseness to supplement previous intuitive concepts and which permits one to use this concept in comparing the quality of different evolutionary reconstructions. This measure is used to examine several published phylogenetic trees: insulin, alpha-hemoglobin, beta-hemoglobin, myoglobin, cytochrome c, and the parvalbumin family. The paper emphasizes 1) the importance of denseness in accurately estimating the number of nucleotide replacements which separate homologous sequences when this estimation is made by the method of parsimony, 2) the value of this concept in assessing the quality of those estimates, and 3) the use of this concept as a biologically practical heuristic method for identifying poorly studied regions in a phylogenetic tree, whether or not the tree was obtained by the parsimony method.

Biological Evolution↗
PubMed1976

Solution of a gene divergence problem under arbitrary stable nucleotide transition probabilities.

A nucleic acid chain L nucleotides in length, with the specific base sequence B1B2....BL, each Bi being A, G, C, or T, is defined by the L-dimensional vector B = (B1, B2, ..., BL), the kth position in the chain being occupied by the base Bk. Let pBB, be the twelve given constant nonnegative transition probabilities that in a specified position the base B is replaced by the base B' in a single step, and let P(X)BB, be the probability that the position goes from base B to B' in X steps. An exact analytical expression for P(X)BB' is derived. Assuming that each base mutates independently of the others, an exact expression is derived for the probability P(X)BB' that the initial gene sequence B goes to a sequence B' = (B'1, B'2; ..., B'L) after X = (X1, X2, ..., XL) base replacements, where Xk is the number of single step base replacements in the kth position. The resulting equations allow a more precise accounting for the effects of Darwinian natural selection in molecular evolution than does the idealized but biologically less accurate assumption that each of the four nucleotides is equally likely to mutate to and be fixed as one of the other three. Illustrative applications of the theory to some problems in biological evolution are given.

Base Sequence↗
PubMed1975

Amino acid composition of proteins: Selection against the genetic code.

Distribution of amino acids in 68 representative proteins is compared with their distribution among 61 codons of the genetic code. Average amounts of lysine, aspartic acid, glutamic acid, and alanine are above the levels anticipated from the genetic code, and arginine, serine, leucine, cysteine, proline, and histidine are below such levels. Arginine plus lysine account for 11.0 percent of codons and aspartic acid plus glutamic acid account for 11.3 percent; thus the average charge is roughly neutral.

Amino Acid Sequence↗
PubMed1975

Tables of critical values for examining compositional non-randomness in proteins and nucleic acids.

A binomially distributed statistic pchi2i is defined which in conjunction with a set of critical tables permits, for peptides or proteins of arbitrary lengths, a well-defined answer to the question: Does the proportion of a particular amino acid iota present in that protein deviate significantly from random expectation? An analogous statistic is defined for nucleic acids. This statistic is simply related to the classical chi-squared test. The classical chi2 and the pchi2i are supplementary in that the former permits one to determine that a non-randomness in amino acid composition exists in a protein, while the latter permits one to localize that non-randomness to particular amino acids. The pchi2i statistic takes into account explicity the compositional fluctuations imposed by the finite length of proteins. The tables are more exact than any hitherto existing, and require no intermediate calculations for their use: from the direct experimental measurement of the number of residues of amino acid iota, one immediately reads from the tables whether the number observed is within random expectation or not. These statistics are used to analyze eight proteins of diverse length, function, and origin in an accompanying paper.

Amino Acids↗
PubMed1975

Deviations from compositional randomness in eukaryotic and prokaryotic proteins: the hypothesis of selective-stochastic stability and a principle of charge conservation.

Eight proteins of diverse lengths, functions, and origin, are examined for compositional non-randomness amino acid by amino acid. The proteins investigated are human fibrinopeptide A, guinea pig Insulin, rattlesnake cytochrome c, MS2 phage coat protein, rabbit triosephosphate isomerase, bovine pancreatic deoxyribonuclease A, bovine glutamate dehydrogenase, and Bacillus thermoproteolyticus thermolysin. As a result of this study the experimentally testable hypothesis is put forth that for a large class of proteins the ratio of that fraction of the molecule which exhibits compositional non-randomness to that fraction which does not is on the average, stable about a mean value (estimated as 0.32 plus or minus 0.17) and (nearly) independent of protein length. Stochastic and selective evolutionary forces are viewed as interacting rather than independent phenomena. With respect to amino acid composition, this coupling ameliorates the current controversy over Darwinian vs. non-Darwinian evolution, selectionist vs. neutralist, in favor of neither: Within the context of the quantitative data, the evolution of real proteins is seen as a compromise between the two viewpoints, both important. The compositional fluctuations of the electrically charged amino acids glutamic and aspartic acid, lysine and arginine, are examined in depth for over eighty protein families, both prokaryotic and eukaryotic. For both taxa, each of the acidic amino acids is present in amounts roughly twice that predicted from the genetic code. The presence of an excess of glutamic acid is independent of the presence of an excess of aspartic acid and vice versa.

Amino Acids↗