Optimal copula duration in yellow dung flies: effects of female size and egg content

We examine data on copula duration in dung flies, Scatophaga stercoraria, in relation to female phenotype. We use a marginal value theorem approach based on the plausible mechanisms of sperm competition to predict the effect of female variation on optimal copula duration, t *, from the male perspective. Future fertilizations are expected to have a trivial effect on t * with fully gravid females, but an increasing relative effect on t * towards completion of oviposition. t * is expected to be affected by female size because of variation in (1) a female's egg content, which increases the maximum egg gain available from a mating, and (2) the female reproductive tract, which affects the rate at which sperm are displaced. In fully gravid females, t * was not dependent on egg number variation, but showed a positive relation with egg content in females that had laid a varying proportion of their mature egg load at the time of mating, and were therefore not fully gravid. Our models predict that if a male can estimate egg content only by the distension of a female's abdomen, t * should increase in a similar way to that seen with 'take-over' females. We predict t * for fully gravid females by assuming that males can monitor female size. The data showed that sperm displacement rate decreased, and average egg content increased, with female size. Under two models for a sperm displacement mechanism, one (which assumes indirect displacement at a rate proportional to the increase in spermathecal volume) predicts the observed relation between t * and female size almost exactly. Small males copulated for longer than large males (as predicted and reported previously). Copyright 1999 The Association for the Study of Animal Behaviour.     

The crystal structure of a high affinity RNA stem-loop complexed with the bacteriophage MS2 capsid: further challenges in the modeling of ligand-RNA interactions

We have determined the structure to 2.8 A of an RNA aptamer (F5), containing 2'-deoxy-2-aminopurine (2AP) at the -10 position, complexed with MS2 coat protein by soaking the RNA into precrystallised MS2 capsids. The -10 position of the RNA is an important determinant of binding affinity for coat protein. Adenine at this position in other RNA stem-loops makes three hydrogen bonds to protein functional groups. Substituting 2AP for the -10 adenine in the F5 aptamer yields an RNA with the highest yet reported affinity for coat protein. The refined X-ray structure shows that the 2AP base makes an additional hydrogen bond to the protein compared to adenine that is presumably the principal origin of the increased affinity. There are also slight changes in phosphate backbone positions compared to unmodified F5 that probably also contribute to affinity. Such phosphate movements are common in structures of RNAs bound to the MS2 T = 3 protein shell and highlight problems for de novo design of RNA binding ligands.     

Sperm morphometry in the Atlantic salmon

This study sampled sperm from wild Atlantic salmon to explore relationships between sperm form and function. Detailed measurements of sperm morphometry (head, flagellum and total length) and sperm activity (longevity and % motility) were made from 24 reproductively active males (13 anadromous and 11 mature parr) on two occasions post-stripping. There was significant between-male variance in total sperm length but this variance was not related to body size. Despite this variance in sperm length, no relationships were found between a male's sperm activity (longevity or % motility) and his sperm length. There were also no relationships between sperm head length and flagellar length, and no evidence for a trade-off between sperm length and numbers. It is suggested that the significant between-male variance in sperm morphometry supports diploid control of spermatogenesis: haploid expression of sperm phenotype would be manifested as profound variance within (and not between) each male's spermatozoal characteristics.     

Improved tests for heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence

The neutral theory of molecular evolution predicts that the ratio of polymorphisms to fixed differences should be fairly uniform across a region of DNA sequence. Significant heterogeneity in this ratio can indicate the effects of balancing selection, selective sweeps, mildly deleterious mutations, or background selection. Comparing an observed heterogeneity statistic with simulations of the heterogeneity resulting from random phylogenetic and sampling variation provides a test of the statistical significance of the observed pattern. When simulated data sets containing heterogeneity in the polymorphism-to-divergence ratio are examined, different statistics are most powerful for detecting different patterns of heterogeneity. The number of runs is most powerful for detecting patterns containing several peaks of polymorphism; the Kolmogorov-Smirnov statistic is most powerful for detecting patterns in which one end of the gene has high polymorphism and the other end has low polymorphism; and a newly developed statistic, the mean sliding G statistic, is most powerful for detecting patterns containing one or two peaks of polymorphism with reduced polymorphism on either side. Nine out of 27 genes from the Drosophila melanogaster subgroup exhibit heterogeneity that is significant under at least one of these three tests, with five of the nine remaining significant after a correction for multiple comparisons, suggesting that detectable evidence for the effects of some kind of selection is fairly common.      

The genetic basis of inbreeding avoidance in house mice

Animals might be able to use highly polymorphic genetic markers to recognize very close relatives and avoid inbreeding. The major histocompatibility complex (MHC) is thought to provide such a marker because it influences individual scent in a broad range of vertebrates. However, direct evidence is very limited. In house mice (Mus musculus domesticus), the major urinary protein (MUP) gene cluster provides another highly polymorphic scent signal of genetic identity that could underlie kin recognition. We demonstrate that wild mice breeding freely in seminatural enclosures show no avoidance of mates with the same MHC genotype when genome-wide similarity is controlled. Instead, inbreeding avoidance is fully explained by a strong deficit in successful matings between mice sharing both MUP haplotypes. Single haplotype sharing is not a good guide to the identification of full sibs, and there was no evidence of behavioral imprinting on maternal MHC or MUP haplotypes. This study, the first to examine wild animals with normal variation in MHC, MUP, and genetic background, demonstrates that mice use self-referent matching of a species-specific polymorphic signal to avoid inbreeding. Recognition of close kin as unsuitable mates might be more variable across species than a generic vertebrate-wide ability to avoid inbreeding based on MHC.     

The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer

Endocrine therapy has successfully been used to treat estrogen receptor (ER)-positive breast cancer, but this invariably fails with cancers becoming refractory to treatment. Emerging evidence has suggested that fluctuations in ER co-regulatory protein expression may facilitate resistance to therapy and be involved in breast cancer progression. To date, a small number of enzymes that control methylation status of histones have been identified as co-regulators of ER signalling. We have identified the histone H3 lysine 9 mono- and di-methyl demethylase enzyme KDM3A as a positive regulator of ER activity. Here, we demonstrate that depletion of KDM3A by RNAi abrogates the recruitment of the ER to cis-regulatory elements within target gene promoters, thereby inhibiting estrogen-induced gene expression changes. Global gene expression analysis of KDM3A-depleted cells identified gene clusters associated with cell growth. Consistent with this, we show that knockdown of KDM3A reduces ER-positive cell proliferation and demonstrate that KDM3A is required for growth in a model of endocrine therapy-resistant disease. Crucially, we show that KDM3A catalytic activity is required for both ER-target gene expression and cell growth, demonstrating that developing compounds which target demethylase enzymatic activity may be efficacious in treating both ER-positive and endocrine therapy-resistant disease.