Search PubMed⌕ Search

Biomedical subjects

R Holmquist

Publications and source records attributed to R Holmquist.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1977

Morphology of extremely heat-resistant spores from Bacillus sp. ATCC 27380 by scanning and transmission electron microscopy.

Bacillus sp. ATCC 27380 is a recently discovered aerobic mesophile, isolated from surface soil, that produces spores with extreme resistance to dry heat: the length of time to 90% kill is 139 hr at 125 degrees C and 13-17 hr at 138 degrees C. Values for spores from other known species range from 5 to 100 min. The molecular basis for this extreme heat resistance is unknown. We report a structural analysis of the internal and external mature spore morphology obtained by both scanning and transmission electron microscopy. Both modes of microscopy delineate a morel-like structure characterized by irregular, but distinct, polygonal ridges suggestive of extreme dehydration. Some spores also possess an appendage resembling the bun of a brioche. This bun-like body is possibly unique to this species. In cross section the spore exhibits a many-layered structure, each layer with a characteristic fine structure. These morphological characters do not suffice to explain the observed resistance to dry heat at extreme temperatures. They do form a basis for the chemical characterizations which will be necessary to understand this heat resistance at the molecular level. The concept of "solid state spore" is put forward as a generalization that may be useful towards understanding this resistance.

Bacillus↗
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↗
PubMed1972

Evolutionary clock: nonconstancy of rate in different species.

By using various methods for comparing polypeptide sequences we find that the evolutionary divergence of rattlesnake cytochrome c from cytochromes c of species in other classes has been more rapid than that of cytochrome c of another reptile, the snapping turtle. This suggests that the evolutionary rate of change of cytochromes c is species-dependent as well as time-dependent.

Amino Acid Sequence↗