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J F Brookfield

Publications and source records attributed to J F Brookfield.

At least 19 recordsLinked to original sources
PubMed1999

What is the impact of transposable elements on host genome variability?

The spread of a transposable element family through a wild population may be of astonishing rapidity. At least three families of transposable genetic elements have recently invaded Drosophila melanogaster worldwide, including the P element. The mechanism has been a process of effectively replicative transposition, and, for the P element, has occurred notwithstanding the sterility induced by unrestricted movement. This element's invasion into D. melanogaster has been accompanied by the development of heterogeneity between P sequences, most of which now have internal deletions. Increasing evidence suggests that some deleted elements can repress P transposition, thereby protecting the host from the harmful effects of complete elements. Such repressing elements may rise to high frequencies in populations as a result of selection at the level of the host. We here investigate selective sweeps invoked by the spread of P sequences in D. melanogaster populations. Numerous high-frequency sites have been identified on the X chromosome, which differ in frequency between populations, and which are associated with repression of P-element transposition. Unexpectedly, sequences adjacent to high-frequency P-element sites do not show reduced levels of genetic diversity, and DNA variability is in linkage equilibrium with the presence or absence of a P element at the adjacent selected site. This might be explained by multiple insertions or through a selection for recombination analogous to that seen in 'hitchhiking'.

Alleles↗
PubMed1999

Myotonic dystrophy: the correlation of (CTG) repeat length in leucocytes with age at onset is significant only for patients with small expansions.

Myotonic dystrophy (DM) was the first of a group of diseases to be identified for which the genetic basis is the expansion of a triplet repeat. Myotonic dystrophy also exhibits anticipation, in which the disease worsens through successive generations. These two features have led many groups to analyse whether a significant negative correlation between triplet repeat length and severity of disease exists. However, the recent molecular finding that two distinct subsets of classically affected DM patients exist, those who export expansion derived DMPK RNA and those who do not, led us to question whether combining data from these two sets of patients is statistically valid. We found that although patients with small expansions showed a significant correlation between age at onset and triplet repeat length, those with larger expansions did not. The theoretical triplet repeat size, which separated the two groups, was also deduced.

Age of Onset↗
PubMed1998

A novel repressor of P element transposition in Drosophila melanogaster.

We have discovered, in an inbred line (Loua) of Drosophila melanogaster from Zaire, a third chromosome showing unusual P element repression. Repression of P element transposition by this chromosome, named Loua3, is dominant zygotic and has three unusual properties. Firstly, its repression of the gonadal dysgenesis caused by a strong P haplotype is strongly temperature-dependent, being most evident at higher rearing temperatures. Secondly, subdivision of Loua3 by recombination abolishes repression: the effect is apparently a function of the intact chromosome. Finally, Loua3 also diminishes somatic lethality when chromosomes carrying many 'ammunition' elements (Birmingham2) are exposed to the constitutive transposase source delta 2-3(99B). The chromosome has 17 P elements, none full-length, located in at least 12 dispersed positions.

Animals↗
PubMed1998

Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia.

OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region. RESULTS: Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission. CONCLUSION: Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion.

Alleles↗
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↗
PubMed1997

Population genetics models of transposable elements.

The control of transposable element copy number is of considerable theoretical and empirical interest. Under simple models, copy numbers may increase without limit. Mechanisms that can prevent such an increase include those in which the effect of selection increases with copy number, those in which the rate of transposition decreases with copy number, and those where unlimited increase in copy number is prevented by the consequences of functional heterogeneity in the transposable element family. Finite population sizes may attenuate the power of natural selection to act on transposable element copy number in a number of ways that may be of particular importance in laboratory populations. First, a small host population size will create occasional periods in which the variance between individuals in copy number is diminished, and with it the power of natural selection, even when the expected variance is Poisson. Second, small population sizes will produce high-frequency transposable element sites, systematically reducing the variance in copy number. The consequences will be particularly profound when the selective damage of transposable elements follows from their heterozygosity, as when ectopic exchange limits copy number.

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↗