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Biomedical subjects

D C Reanney

Publications and source records attributed to D C Reanney.

17 recordsLinked to original sources

RNA splicing as an error-screening mechanism.

Eukaryote nuclear genes are generally split into coding (exon) and noncoding (intron) regions. During the formation of messenger RNA the introns are precisely excised and the exons religated. A widely accepted explanation for the split structure of eukaryotic genes is that proposed by Gilbert who hypothesized that the division of coding information into small units speeded up the rate of protein evolution by allowing for the recombination of the independent peptide domains encoded by these units ("exon shuffling"). However it has recently become clear that the exon:intron structure of genes most likely preceded the uninterrupted form. This makes it difficult to accept Gilbert's argument as it applies to the origin(s) of split genes since early genes were very inaccurately copied and a highly error-prone system needs less variation not more. Here I propose that split genes and the concomitant process of RNA splicing arose as a mechanism for maintaining the stability of the genetic information in the face of a high level of noise in the gene copier mechanism.

Base Sequence

Temperature as a determinative factor in the evolution of genetic systems.

Heat induces a number of premutational lesions (for example, the deamination of cytosine to uracil) in DNA and RNA. These kinds of errors occur in resting as well as replicating polynucleotides. However, an increase in temperature also raises the probability of copying error occurring in nucleic acids because of increased thermal noise in the replicative machinery. In most modern genetic systems, the majority of heat-induced lesions are efficiently repaired. It follows that the importance of heat-induced error increases as the effectiveness of repair declines. We show in this paper that the error rate of enzymatic polynucleotide copying is expected to increase monotonically with temperature. We also explore the effects of temperature variations on the early evolution of biological information transmission mechanisms.

Biological Evolution

Divided genomes and intrinsic noise.

Segmental genomes (i.e., genomes in which the genetic information is dispersed between two or more discrete molecules) are abundant in RNA viruses, but virtually absent in DNA viruses. It has been suggested that the division of information in RNA viruses expands the pool of variation available to natural selection by providing for the reassortment of modular RNAs from different genetic sources. This explanation is based on the apparent inability of related RNA molecules to undergo the kinds of physical recombination that generate variation among related DNA molecules. In this paper we propose a radically different hypothesis. Self-replicating RNA genomes have an error rate of about 10(-3) - 10(-4) substitutions per base per generation, whereas for DNA genomes the corresponding figure is 10(-9) - 10(-11). Thus the level of noise in the RNA copier process is five to eight orders of magnitude higher than that in the DNA process. Since a small module of information has a higher chance of passing undamaged through a noisy channel than does a large one, the division of RNA viral information among separate small units increases its overall chances of survival. The selective advantage of genome segmentation is most easily modelled for modular RNAs wrapped up in separate viral coats. If modular RNAs are brought together in a common viral coat, segmentation is advantageous only when interactions among the modular RNAs are selective enough to provide some degree of discrimination against miscopied sequences. This requirement is most clearly met by the reoviruses.

Biological Evolution

Preparation of plasmid DNA by gamma-irradiation of recA cells.

If recA bacteria are exposed to appropriate doses of gamma-irradiation, nondividing cells which can sustain the multiplication of "small" plasmids are produced. The gamma-irradiation technique has a number of advantages over other methods for preparing pure plasmid DNA: (1) there is little, if any, contamination of DNA preparations by chromosomal DNA owing to extensive degradation of the irradiated DNA by endogenous nucleases, (2) there is no need to introduce a uvr mutation to the host bacteria (there is when UV is used to inactivate the chromosome), (3) the method is extremely simple to work with since operations are not limited by considerations of volume and cell density, and (4) there is no need to transfer material from container to container. Yields of plasmid DNA obtained by the gamma-irradiation technique compare favorably with those obtained by other methods.

Cloning, Molecular

Intrinsic noise and the design of the genetic machinery.

Darwinian theory envisages 'selection pressure' as a stress imposed on the genotype by the environment. However, noise in the replicative and translational mechanisms in itself imposes a significant 'pressure' on the adaptive fitness of the organism. We propose that the biosphere has been shaped by both extrinsic (environmental) and intrinsic (noise-generated) factors. Because noise has been a remorseless and ever-present background to the evolutionary process, adaptations to this intrinsic pressure include not only a variety of familiar genetic mechanisms but also many anatomical and life-style characteristics that focus on the transmission of information between generations.

Animals

Translocatable resistance to mercuric and phenylmercuric ions in soil bacteria.

Of a sample of 42 gram-negative Hg-resistant bacteria, three (a Pseudomonas fluorescens, a Klebsiella sp. and a Citrobacter sp.) contained translocatable elements conferring resistance to Hg2+ (all three) and to Hg2+ and phenylmercuric acetate (P. fluorescens). The discovery of transposable phenylmercuric acetate resistance extends the range of known resistance "transposons" from heavy metals and antibiotics to organometallic compounds.

Bacteria