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Biomedical subjects

D G Higgins

Publications and source records attributed to D G Higgins.

46 records · Page 3Linked to original sources
PubMed1989

Fast and sensitive multiple sequence alignments on a microcomputer.

A strategy is described for the rapid alignment of many long nucleic acid or protein sequences on a microcomputer. The program described can handle up to 100 sequences of 1200 residues each. The approach is based on progressively aligning sequences according to the branching order in an initial phylogenetic tree. The results obtained using the package appear to be as sensitive as those from any other available method.

Algorithms↗
PubMed1989

Replication and segregational stability of Bacillus plasmid pBAA1.

A cryptic plasmid, pBAA1, was identified in an industrial Bacillus strain. The plasmid is 6.8 kilobases in size and is present in cells at a copy number of approximately 5 per chromosome equivalent. The plasmid has been maintained under industrial fermentation conditions without apparent selective pressure and so is assumed to be partition proficient. The minimal replicon was localized to a 1.4-kilobase fragment which also contains the functions required for copy number control. The very low level of segregational instability of the minimal replicon suggests that it also contains functions involved in plasmid maintenance. Comparison with other plasmids indicates that pBAA1 belongs to the group of small gram-positive plasmids which replicate by a rolling cycle-type mechanism. A sequence was identified which is required for the efficient conversion of the single plus strand to the double-stranded form during plasmid replication. Deletion of this sequence resulted in a low level of segregational plasmid instability.

Amino Acid Sequence↗
PubMed1988

CLUSTAL: a package for performing multiple sequence alignment on a microcomputer.

An approach for performing multiple alignments of large numbers of amino acid or nucleotide sequences is described. The method is based on first deriving a phylogenetic tree from a matrix of all pairwise sequence similarity scores, obtained using a fast pairwise alignment algorithm. Then the multiple alignment is achieved from a series of pairwise alignments of clusters of sequences, following the order of branching in the tree. The method is sufficiently fast and economical with memory to be easily implemented on a microcomputer, and yet the results obtained are comparable to those from packages requiring mainframe computer facilities.

Algorithms↗
PubMed1988

Codon usage patterns in Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens; a review of the considerable within-species diversity.

The genetic code is degenerate, but alternative synonymous codons are generally not used with equal frequency. Since the pioneering work of Grantham's group it has been apparent that genes from one species often share similarities in codon frequency; under the "genome hypothesis" there is a species-specific pattern to codon usage. However, it has become clear that in most species there are also considerable differences among genes. Multivariate analyses have revealed that in each species so far examined there is a single major trend in codon usage among genes, usually from highly biased to more nearly even usage of synonymous codons. Thus, to represent the codon usage pattern of an organism it is not sufficient to sum over all genes as this conceals the underlying heterogeneity. Rather, it is necessary to describe the trend among genes seen in that species. We illustrate these trends for six species where codon usage has been examined in detail, by presenting the pooled codon usage for the 10% of genes at either end of the major trend. Closely-related organisms have similar patterns of codon usage, and so the six species in Table 1 are representative of wider groups. For example, with respect to codon usage, Salmonella typhimurium closely resembles E. coli, while all mammalian species so far examined (principally mouse, rat and cow) largely resemble humans.

Amino Acids↗
PubMed1988

"Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons.

The patterns of synonymous codon usage in 91 Drosophila melanogaster genes have been examined. Codon usage varies strikingly among genes. This variation is associated with differences in G+C content at silent sites, but (unlike the situation in mammalian genes) these differences are not correlated with variation in intron base composition and so are not easily explicable in terms of mutational biases. Instead, those genes with high G+C content at silent sites, resulting from a strong "preference" for a particular subset of the codons that are mostly C-ending, appear to be the more highly expressed genes. This suggests that G+C content is reduced in sequences where selective constraints are weaker, as indeed seen in a pseudogene. These and other data discussed are consistent with the effects of translational selection among synonymous codons, as seen in unicellular organisms. The existence of selective constraints on silent substitutions, which may vary in strength among genes, has implications for the use of silent molecular clocks.

Animals↗
PubMed1987

Interfacing similarity search software with the sequence retrieval system ACNUC.

A method of interfacing sequence similarity search software with the fast sequence retrieval system ACNUC is described. The method is written in FORTRAN 77 and is straightforward to implement because no text-processing code is required--a minimum of 12 extra lines of FORTRAN provided the interface for most applications. The method is also efficient, since sequences are located by simple indexing techniques, with no linear searches of large database files necessary.

Algorithms↗