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Biomedical subjects

D G Higgins

Publications and source records attributed to D G Higgins.

At least 37 records · Page 2Linked to original sources
PubMed1994

Evolution of cytochrome oxidase, an enzyme older than atmospheric oxygen.

Cytochrome oxidase is a key enzyme in aerobic metabolism. All the recorded eubacterial (domain Bacteria) and archaebacterial (Archaea) sequences of subunits 1 and 2 of this protein complex have been used for a comprehensive evolutionary analysis. The phylogenetic trees reveal several processes of gene duplication. Some of these are ancient, having occurred in the common ancestor of Bacteria and Archaea, whereas others have occurred in specific lines of Bacteria. We show that eubacterial quinol oxidase was derived from cytochrome c oxidase in Gram-positive bacteria and that archaebacterial quinol oxidase has an independent origin. A considerable amount of evidence suggests that Proteobacteria (Purple bacteria) acquired quinol oxidase through a lateral gene transfer from Gram-positive bacteria. The prevalent hypothesis that aerobic metabolism arose several times in evolution after oxygenic photosynthesis, is not sustained by two aspects of the molecular data. First, cytochrome oxidase was present in the common ancestor of Archaea and Bacteria whereas oxygenic photosynthesis appeared in Bacteria. Second, an extant cytochrome oxidase in nitrogen-fixing bacteria shows that aerobic metabolism is possible in an environment with a very low level of oxygen, such as the root nodules of leguminous plants. Therefore, we propose that aerobic metabolism in organisms with cytochrome oxidase has a monophyletic and ancient origin, prior to the appearance of eubacterial oxygenic photosynthetic organisms.

Aerobiosis↗
PubMed1994

The evolution of titin and related giant muscle proteins.

Titin and twitchin are giant proteins expressed in muscle. They are mainly composed of domains belonging to the fibronectin class III and immunoglobulin c2 families, repeated many times. In addition, both proteins have a protein kinase domain near the C-terminus. This paper explores the evolution of these and related muscle proteins in an attempt to determine the order of events that gave rise to the different repeat patterns and the order of appearance of the proteins. Despite their great similarity at the level of sequence organization, titin and twitchin diverged from each other at least as early as the divergence between vertebrates and nematodes. Most of the repeating units in titin and twitchin were estimated to derive from three original domains. Chicken smooth-muscle myosin light-chain kinase (smMLCK) also has a kinase domain, several immunoglobulin domains, and a fibronectin domain. From a comparison of the kinase domains, titin is predicted to have appeared first during the evolution of the family, followed by twitchin and with the vertebrate MLCKs last to appear. The so-called C-protein from chicken is also a member of this family but has no kinase domain. Its origin remains unclear but it most probably pre-dates the titin/twitchin duplication.

Animals↗
PubMed1994

Improved sensitivity of profile searches through the use of sequence weights and gap excision.

Position-specific substitution matrices, known as profiles, derived from multiple sequence alignments are currently used to search sequence databases for distantly related members of protein families. The performance of the database searches is enhanced by using (i) a sequence weighting scheme which assigns higher weights to more distantly related sequences based on branch lengths derived from phylogenetic trees, (ii) exclusion of positions with mainly padding characters at sites of insertions or deletions and (iii) the BLOSUM62 residue comparison matrix. A natural consequence of these modifications is an improvement in the alignment of new sequences to the profiles. However, the accuracy of the alignments can be further increased by employing a similarity residue comparison matrix. These developments are implemented in a program called PROFILEWEIGHT which runs on Unix and Vax computers. The only input required by the program is the multiple sequence alignment. The output from PROFILEWEIGHT is a profile designed to be used by existing searching and alignment programs. Test results from database searches with four different families of proteins show the improved sensitivity of the weighted profiles.

Algorithms↗
PubMed1994

Molecular evidence for the inclusion of cetaceans within the order Artiodactyla.

The transition in the cetaceans from terrestrial life to a fully aquatic existence is one of the most enduring evolutionary mysteries. Resolving the phylogenetic relationships between Cetacea and the other orders of eutherian mammals may provide us with important clues to the origin of whales and may help us date the evolutionary transition to aquatic life. Previous paleontological and molecular evidence has indicated that cetaceans and artiodactyls constitute a natural clade within subclass Eutheria. Our present phylogenetic analyses of protein and mitochondrial DNA sequence data indicate that cetaceans are not only intimately related to the artiodactyls; they are in fact deeply nested within the artiodactyl phylogenetic tree; i.e., they are more closely related to the members of one suborder of artiodactyls, the Ruminantia, than either ruminants or cetaceans are to members of the other two artiodactyl suborders: Suiformes and Tylopoda. On the basis of the rate of evolution of mitochondrial DNA sequences and using paleontological reference dates for calibration, we estimate that the whale lineage has branched off a protoruminant lineage < 50 Mya. By implication, the cetacean transition to aquatic life is inferred to be a relatively recent evolutionary event.

Animals↗
PubMed1993

The Phylogeny of malaria: a useful study.

Phylogenetic analyses allow an inference of the origins and evolutionary relationships between organisms. Andy Waters, Des Higgins and Tom McCutchan here discuss the benefits of an accurate understanding of these origins and relationships for malaria parasites to the modern fields of vaccine development, pathology and epidemiology.

Journal Article↗
PubMed1993

Evolutionary relatedness of some primate models of Plasmodium.

Primate--and, specifically, monkey--malaria infections are commonly used for understanding the pathology of and immune response to the human disease because they are thought to resemble most closely the host-parasite relationship found in humans. Plasmodium cynomolgi is used extensively as a model for the human parasite, P. vivax, and P. knowlesi is used primarily as a model for the development of erythrocytic-stage vaccines. Both of these simian parasites can naturally infect man, resulting in mildly symptomatic episodes of the disease. The phylogenetic relationship between these two simian parasites and previously characterized Plasmodium species, including P. vivax, was examined by comparison of the asexually expressed small-subunit ribosomal RNA genes. Our analysis confirmed that P. vivax is most closely related to P. cynomolgi and that it remains an appropriate model of the human pathogen. Furthermore, with P. knowlesi and P. fragile, these two species form a group of closely related species, distant from other Plasmodium species. What is considered to be the most ancient of the human malaria pathogens, P. malariae, was also included in the analysis and does not group at all with other simian or human parasites.

Animals↗
PubMed1992

Sequence ordinations: a multivariate analysis approach to analysing large sequence data sets.

Ordination is a powerful method for analysing complex data sets but has been largely ignored in sequence analysis. This paper shows how to use principal coordinates analysis to find low-dimensional representations of distance matrices derived from aligned sets of sequences. The method takes a matrix of Euclidean distances between all pairs of sequence and finds a coordinate space where the distances are exactly preserved. The main problem is to find a measure of distance between aligned sequences that is Euclidean. The simplest distance function is the square root of the percentage difference (as measured by identities) between two sequences, where one ignores any positions in the alignment where there is a gap in any sequence. If one does not ignore positions with a gap, the distances cannot be guaranteed to be Euclidean but the deleterious effects are trivial. Two examples of using the method are shown. A set of 226 aligned globins were analysed and the resulting ordination very successfully represents the known patterns of relationship between the sequences. In the other example, a set of 610 aligned 5S rRNA sequences were analysed. Sequence ordinations complement phylogenetic analyses. They should not be viewed as a complete alternative.

Amino Acid Sequence↗
PubMed1992

EMBLSCAN: fast approximate DNA database searches on compact disc.

An algorithm that allows rapid searching of nucleic acid sequences based on pregenerated index files is described. The programs and index files for searching the entire EMBL nucleotide sequence collection are being distributed on the EMBL Data Library's CD-ROM.

Algorithms↗
PubMed1992

CLUSTAL V: improved software for multiple sequence alignment.

The CLUSTAL package of multiple sequence alignment programs has been completely rewritten and many new features added. The new software is a single program called CLUSTAL V, which is written in C and can be used on any machine with a standard C compiler. The main new features are the ability to store and reuse old alignments and the ability to calculate phylogenetic trees after alignment. The program is simple to use, completely menu driven and on-line help is provided.

Phylogeny↗
PubMed1992

GCWIND: a microcomputer program for identifying open reading frames according to codon positional G+C content.

GCWIND is a microcomputer (IBM-PC compatible) program for the identification of protein-coding open reading frames. The program is similar to the FRAME program, but the latter has only been implemented for a specialized graphics package. The base compositions (%G+C) for each of the three possible reading phases through the DNA sequence are displayed separately, together with the positions of potential translation initiation and termination codons (on the leading and complementary strands), to provide an immediate representation of those regions within the sequence that have coding potential.

Codon↗
PubMed1991

The salmon gene encoding apolipoprotein A-I: cDNA sequence, tissue expression and evolution.

A cDNA encoding an apolipoprotein (Apo) has been isolated from the Atlantic salmon (Salmo salar) and sequenced. It encodes a peptide of 258 amino acids (aa), including a signal peptide of 18 aa, with 5'- and 3'-untranslated regions of the mRNA of 12 and 329 nucleotides, respectively. The protein has structural features in common with other Apo's of human and avian origin, including conserved sequences in the signal peptide and a series of internal repeats of 22 aa. The sequence has been identified as salmon Apo A-I (sApoA-I), and has 23% aa identity with human ApoA-I. Northern-blot analysis using the sApoA-I cDNA probe against total RNA prepared from several salmon tissues detects the expression of this gene in liver, intestine and muscle. A phylogenetic analysis reveals that the mammalian ApoA-I, ApoA-IV and Apo-E aa sequences are more closely related to each other than any of them are to sApoA-I. This suggests that the duplication events, from which A-I, A-IV and E arose, occurred after the divergence of the tetrapod and teleost ancestors.

Amino Acid Sequence↗
PubMed1991

Plasmodium falciparum appears to have arisen as a result of lateral transfer between avian and human hosts.

It has been proposed that the acquisition of Plasmodium falciparum by man is a relatively recent event and that the sustained presence of this disease in man is unlikely to have been possible prior to the establishment of agriculture. To establish phylogenetic relationships among the Plasmodium species and to unravel the mystery of the origin of P. falciparum, we have analyzed and compared phylogenetically the small-subunit ribosomal RNA gene sequences of the species of malaria that infect humans as well as a number of those sequences from species that infect animals. Although this comparison confirmed the three established major subgroups, broadly classed as avian, simian, and rodent, we find that the human pathogen P. falciparum is monophyletic with the avian subgroup, indicating that P. falciparum and avian parasites share a relatively recent avian progenitor. The other important human pathogen, P. vivax, is very similar to a representative of the simian group of Plasmodium. The relationship between P. falciparum and the avian parasites, and the overall phylogeny of the genus, provides evidence of an exception to Farenholz's rule, which propounds synchronous speciation between host and parasite.

Animals↗
PubMed1991

Molecular phylogeny of the subgenus Sophophora of Drosophila derived from large subunit of ribosomal RNA sequences.

RNA sequencing has been used to assess the relationships among species of the subgenus Sophophora of the genus Drosophila. Two divergent domains, D1 and D2, of the large ribosomal RNA (28S), totalling 550 nucleotides have been sequenced using the rRNA direct sequencing method. A tree has been reconstructed from the neighbor-joining algorithm and the confidence intervals were evaluated by the bootstrap procedure. Results have shown that the branching of the willistoni and saltans groups of the subgenus Sophophora is very ancient and probably predates that of the subgenus Drosophila. The other groups and subgroups of Sophophora are clustered in three main lineages: 1) the melanogaster and oriental subgroups; 2) the montium subgroup; 3) the ananassae subgroup of the melanogaster group clustered with the fima and obscura groups. Thus, in comparison with our results, several taxa of various ranks appear paraphyletic (the genus Drosophila, the subgenus Sophophora and the melanogaster group). Our biochemical phylogeny is only in partial agreement with the pattern of Throckmorton's radiations as well as with classical taxonomy, both based on morphological data.

Animals↗