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Biomedical subjects

J F Brookfield

Publications and source records attributed to J F Brookfield.

At least 19 recordsLinked to original sources
PubMed1997

The role of host factors in the population dynamics of selfish transposable elements.

Previous models of the evolution of selfish transposable genetic elements have failed to include the possibility that transposition may be limited by shortage of a host-encoded factor. The titration of host factors may be important in limiting the rate of transpositional increase in these elements. This will be exacerbated if multiple copies of the host factor protein must bind simultaneously to the target element. In the case of the Drosophila melanogaster P transposable element, which can exist as autonomous and as non-autonomous copies, there is evidence that a host-encoded protein, IRBP, is required for the transposition process. We have produced a specific model of the invasion of a host population by the P element, in which we have incorporated the requirement for the multiple binding of a host factor. We find that, for the P family, in which it is apparently transposition itself that creates selective harm to the host, the effect of selection in the context of host factor limitation is to drive up copy number. This can result in a novel high copy number-low transposition state. We also find that host factor limitation reinforces the tendency for transposable elements that create sterility to be replaced by their deletion derivatives.

Animals↗
PubMed1997

Genetic redundancy: screening for selection in yeast.

An unexpectedly large proportion of eukaryotic genes yield no obvious mutant phenotype when inactivated. An ingenious new approach using yeast allows all genes to be screened simultaneously for the presence of weak selection against lack-of-function mutations.

Genes, Fungal↗
PubMed1997

Hypothesis testing in evolutionary inference.

The comparative method, amongst other things, searches for correlations between evolutionary variables. These can be used to test null hypotheses. Here I consider, in the context of binary variables, the bases of such tests. I examine grounds upon which evolutionary traits and events can be regarded as statistically independent of each other. I argue that no description of observations as independent or non-independent makes sense except in the context of a population of possible observations from which they are regarded as having being sampled. Significant correlations between traits or changes in traits in comparative tests have been taken by some to imply causal links between traits. However, the statistical significance of an observed correlation between traits is neither necessary nor sufficient for the inference of a causal connection between them.

Animals↗
PubMed1996

Genetic evidence for repression of somatic P element movements in Drosophila melanogaster consistent with a role for the KP element.

The P family of transposable elements in Drosophila melanogaster has, since its introduction into D. melanogaster populations in this century, diversified into a number of internally deleted forms. One of these, the KP element, is abundant in the genomes of flies from populations from Asia, Europe and Africa. There is some evidence that this sequence can act as a repressor of transposition. We have studied a mutation, signed(very weak) (snVW), in which a KP element is one of two P elements inserted into the 5' exon of the X-linked singed gene. These elements can be mobilized by a trans-acting dominant mutation, Mo, with a maternal effect, on the second chromosome. The rate of somatic reversion of snvw induced by Mo is reduced threefold if the mother herself possesses snvw on her X chromosomes. This implies that snvw may be responsible for a form of repression of P element movement. The cause of this effect may be related to transcription of the KP element in snvw. However, an effect of other genomic P elements in the repression of somatic reversion of snvw cannot be entirely excluded.

Animals↗
PubMed1995

A test for adaptive change in DNA sequences controlling transcription.

Spatial and temporal differences in gene expression in early development result from the interaction of transcription factors with enhancer and silencer sequences in DNA. The evolution of the developmental process thus involves changes in the DNA sequences that bind transcription factors. Here we advocate a non-parametric statistical test-comparing levels of polymorphism and fixed substitutions between species -to look for evidence of adaptive evolution in sequences controlling gene expression. The test is illustrated by DNA sequence changes in the proximal part of the 'zebra' elements in the fushi terazu gene of the Drosophila melanogaster species group, which yield significant evidence for adaptive substitutions. (This is despite highly significant evidence that all parts of the sequence have been subject to strong selective constraint). The test can be applied generally to investigate adaptive evolution in the control of gene expression.

Animals↗
PubMed1995

Molecular evolution. Retroposon revivals.

Phylogenetic studies of the mouse L1 retroposon family show that the elements evolve through successively active subfamilies, which differ from each other by complete replacements of their promoter sequences.

Animals↗
PubMed1995

Statistical issues in DNA evidence.

Some of the statistical issues involved in the interpretation of DNA evidence in courts, particularly focusing on the adversarial process as seen in the UK and the USA, are discussed. The appropriate way to consider the use of DNA evidence in courts is through the use of a likelihood ratio. In this, the relative likelihoods of the DNA evidence are calculated under two hypotheses, respectively that the subject is or is not the source of a DNA sample found at the scene-of-crime. This formulation allows, using Bayes' theory, the prior probability of guilt, based on the other evidence in a case, to be incorporated in a formal way into calculation of a final, or posterior, probability of guilt. The most controversial aspect of DNA evidence has concerned the calculation of the probability of a match between an innocent suspect and DNA from the scene-of-crime. The calculation is affected by subdivision within the population and the possibility of relatedness between the suspect and the true source of the scene-of-crime DNA. The qualitative importance of these effects will be discussed. In addition to the scientific questions concerning the likelihood ratio, there have been a number of other concerns about the use of DNA evidence, and other evidence presented in a statistical form, in courts. These include the question whether accurate or conservative values of the likelihood ratio should be presented, and the abilities of juries to deal with quantitative evidence.

DNA↗
PubMed1995

Chromosomal distribution and population dynamics of the 412 retrotransposon in a natural population of Drosophila melanogaster.

The localization of the insertion sites of the 412 retrotransposable element was analysed by in situ hybridization to the polytene chromosomes of the genomes of males from a natural population of Drosophila melanogaster. Non-parametric statistical tests do not reveal any particular distribution of the insertion sites over the chromosomes, suggesting an apparently random distribution of the 412 element. Aggregation and dispersion tests were highly significant with data of copy number (when all genomes are pooled, many copies may be at a given site), suggesting the existence of sites with high insertion frequency. Comparison with other data from the literature confirms the tendency for a low proportion of insertions on the X chromosome in comparison with the autosomes, a result in agreement with selection acting against the detrimental effect of the 412 element insertions.

Animals↗
PubMed1995

The effect of relatedness on likelihood ratios and the use of conservative estimates.

DNA profiling can be used to identify criminals through their DNA matching that left at the scene of a crime. The strength of the evidence supplied by a match in DNA profiles is given by the likelihood ratio. This, in turn, depends upon the probability that a match would be produced if the suspect is innocent. This probability could be strongly affected by the possibility of relatedness between the suspect and the true source of the scene-of-crime DNA profile. Methods are shown that allow for the possibility of such relatedness, arising either through population substructure or through a family relationship. Uncertainties about the likelihood ratio have been taken as grounds for the use of very conservative estimates of this quantity. The use of such conservative estimates can be shown to be neither necessary nor harmless.

Alleles↗
PubMed1994

Human evolution. A new molecular view of human origins.

Polymorphic microsatellite DNA sequences have been used as a guide to the phylogenetic tree of human populations. There are conceptual as well as empirical problems in the construction and interpretation of such trees.

Animals↗
PubMed1994

The human Alu SINE sequences--is there a role for selection in their evolution?

The Alu sequence is a SINE (Short INterspersed Element) that is abundant in the human genome. A new analysis (1) reveals an unexpected conservation of some bases in the DNA sequence of the element. The bases involved include those forming an RNA polymerase III promoter. An unresolved question is whether this conservation results from selection for transposability. This, in turn, is related to the larger question of the evolutionary relationship between members of the Alu sequence family.

Consensus Sequence↗
PubMed1994

The molecular basis of instability of the singed(very weak) mutation in Drosophila melanogaster.

The singed(very weak) mutation was created by the sequential addition of two P transposable elements to the singed gene. The mutation can be somatically unstable through the action of a dominant maternal effect mutation on the second chromosome. It is also unstable in the germ line in these conditions. Sequencing of the region of the P insertions in the mutation reveals that the two inserted elements have single internal deletions, and the larger of the two is a copy of the KP element. The mutation will generate, at high frequencies, strongly singed and pseudo-wild type products by reversions occurred in the germline. These are the result of the precise excision of the smaller and the larger elements respectively. By PCR amplification of dissected thoraces we show that the somatic instability of the mutation, from a weak to a strong singed phenotype, is also caused by the excision of the smaller of the two elements.

Animals↗