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Cambridge, United Kingdom

Amos W.,Downing Street
Biology Letters | Year: 2016

Whole genome sequencing of families of Arabidopsis has recently lent strong support to the heterozygote instability (HI) hypothesis that heterozygosity locally increases mutation rate. However, there is an important theoretical difference between the impact on base substitutions, where mutation rate increases in regions surrounding a heterozygous site, and the impact of HI on sequences such as microsatellites, where mutations are likely to occur at the heterozygous site itself. At microsatellite loci, HI should create a positive feedback loop, with heterozygosity and mutation rate mutually increasing each other. Direct support for HI acting on microsatellites is limited and contradictory. I therefore analysed AC microsatellites in 1163 genome sequences from the 1000 genomes project. I used the presence of rare alleles, which are likely to be very recent in origin, as a surrogate measure of mutation rate. I show that rare alleles are more likely to occur at locus-population combinations with higher heterozygosity even when all populations carry exactly the same number of alleles. © 2016 The Author(s) Published by the Royal Society. All rights reserved.


Miguel-Aliaga I.,Downing Street
Seminars in Cell and Developmental Biology | Year: 2012

The increasingly recognized role of gastrointestinal signals in the regulation of food intake, insulin production and peripheral nutrient storage has prompted a surge of interest in studying how the gastrointestinal tract senses and responds to nutritional information. Identification of metabolically important intestinal nutrient sensors could provide potential new drug targets for the treatment of diabetes, obesity and gastrointestinal disorders. From a more fundamental perspective, the study of intestinal chemosensation is revealing novel, non-neuronal modes of communication involving differentiated epithelial cells. It is also identifying signalling mechanisms downstream of not only canonical receptors but also nutrient transporters, thereby supporting a chemosensory role for " transceptors" in the intestine. This review describes known and proposed mechanisms of intestinal carbohydrate, protein and lipid sensing, best characterized in mammalian systems. It also highlights the potential of invertebrate model systems such as C. elegans and Drosophila melanogaster by summarizing known examples of molecular evolutionary conservation. Recently developed genetic tools in Drosophila, an emerging model system for the study of physiology and metabolism, allow the temporal, spatial and high-throughput manipulation of putative intestinal sensors. Hence, fruit flies may prove particularly suited to the study of the link between intestinal nutrient sensing and metabolic homeostasis. © 2012 Elsevier Ltd.


Harper E.M.,Downing Street
Memoirs of the Association of Australasian Palaeontologists | Year: 2011

Although there is strong evidence that a range of predatory taxa do attack rhynchonelliform brachiopods in their natural environments, we currently lack sufficient data to establish how important such interactions might be. This contribution is an attempt to draw together and critically review the sparse and scattered data which exist, and to suggest areas for future collection of data.


Danilova M.V.,RAS Pavlov Institute of Physiology | Mollon J.D.,Downing Street
Journal of the Optical Society of America A: Optics and Image Science, and Vision | Year: 2012

We measured chromatic discrimination under conditions where the target fields could be distinguished only by the ratio of excitation of the long-(L) and middle-wavelength (M) cones. The excitation level of the short-wavelength (S) cones was varied in the experiments, although for any given measurement the S-cone excitation was common to the two target fields and could not be directly used for discrimination. Adaptation was maintained by a steady neutral background metameric to Illuminant D65. Thresholds varied substantially and systematically with the S-cone level of the target probes, but in a complex way: when the ratio of L:M cone excitation was low, an increase in S-cone excitation reduced the thresholds, but when the L:M ratio was higher, an increase in Scone excitation raised the thresholds. To account for the pattern of results, we postulate a neural channel that draws synergistic inputs from L and S cones and an opposed input from M cones. The proposed channel has a compressive response function and is most sensitive at the point set by the steady background. © 2012 Optical Society of America.


Majerus T.M.O.,University of Nottingham | Majerus M.E.N.,Downing Street
Evolutionary Ecology | Year: 2012

Male-killing endosymbionts have been widely reported in the invertebrates and are highly prevalent in the Coccinellidae. The presence of male-killers can lead to extreme bias in host population sex ratios and may have important and far-reaching consequences for the life-history and evolution of their hosts. Male-killers may have direct and indirect effects on host fitness and reproductive behaviour, as well as affecting the host genome, either via strong selection pressure imposed by highly female-biased population sex ratios or by selective sweeps caused as a male-killer conferring an advantage to infected individuals spreads through a population. Criteria used to predict which species are liable to male-killer invasion, based on a variety of ecological factors, have been produced. In summary male-killers are predicted to occur in aphidophageous species, that lay eggs in clutches, show sibling egg consumption and are liable to neonatal larval mortality due to starvation. We assayed 30 species of Coccinellid for the presence of such male-killers to assess the predictive accuracy of the criteria. Male-killers were identified in 8 species in which they were predicted to occur and were absent from all 10 species predicted not to harbor them. Analysis of the remaining 12 species, where male-killers were predicted by the original criteria, but where they were not found, allowed us to identify areas where the criteria can be refined and improved. We conclude that whilst the original criteria give a reasonably accurate prediction, there are refinements and improvements, concerning details of host diet and life-history, which make them more robust, especially in the light of discoveries of male-killing suppressors and when incorporated give a better fit to our findings from field samples. © 2011 Springer Science+Business Media B.V.

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