Detecting non-neutral heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence

Natural selection, in the form of balancing selection or selective sweeps, can result in a decoupling of the amounts of molecular polymorphism and divergence. Thus natural selection can cause some areas of DNA sequence to have greater silent polymorphism, relative to divergence between species, than other areas. It would be useful to have a statistical test for heterogeneity in the polymorphism to divergence ratio across a region of DNA sequence, one that could identify heterogeneity greater than that expected from the neutral processes of mutation, drift, and recombination. The only currently available test requires that a region be arbitrarily divided into sections that are compared with each other, and the subjectivity of this division could be problematic. Here a test is proposed in which runs of polymorphic and fixed sites are counted, where a "run" is a set of one or more sites of one type preceded and followed by the other type. The number of runs is smaller than otherwise expected if polymorphisms are clumped together. By simulating neutral evolution and comparing the observed number of runs to the simulations, a statistical test is possible which does not require any a priori decisions about subdivision.      

Effects of water restriction on digestive function in two macropodid marsupials from divergent habitats and the feral goat

The effects of water restriction on digestive function in the euro (Macropus robustus erubescens) found in the arid zone of inland Australia, the eastern wallaroo (M.r.robustus) from more mesic regions of eastern Australia, and the feral goat (Capra hircus) found throughout the range of M. robustus, were compared in order to examine some physiological adaptations required by herbivores for the exploitation of arid environments. Eight animals of each species were held in individual metabolism cages in temperature-moderated rooms and given a chopped hay diet ad libitum. Half the animals were restricted to 40 ml water·kg^-0.80·day^-1. This was 40%, 32% and 57% of voluntary drinking water intake in the euro, wallaroo and goat, respectively. All species responded to water restriction by reducing faecal, urinary and evaporative water losses in association with reductions in feed intake. All animals increased urine osmolality and electrolyte concentrations but not to maximal levels, while packed-cell volume and plasma osmolality and electrolyte concentrations were unaffected by water restriction. The euro displayed a suite of characteristics that separated it from the wallaroo in terms of physiological adaptation, including lower voluntary water intake, an increase in fibre digestibility and maintenance of nitrogen balance during water restriction, and lower faecal water efflux associated with a consistently lower faecal water content (54% versus 59% water in the wallaroo during water restriction, P<0.05). The euro's colon was 37% longer (P<0.01) than that of the wallaroo. The goat had the lowest faecal water efflux (P<0.05) and the longest colon (P<0.001). Water restriction did not affect water content in digesta, nor short-chain fatty acid concentrations or production rates in vitro. Total body water, as a proportion of body mass, was depressed (P<0.05) in the macropodids, but not in the goat. The reduction in dietary nitrogen intake, which accompanied water restriction, was partially compensated by an increase in urea degradation in the gut from 68% to 76% of urea synthesis water-restricted macropodids. These responses to water restriction are discussed in relation to those reported in other macropodid and ruminant species.Abbreviations BM body mass - SCFA short-chain fatty acids - DM dry matter - PCV packed-cell volume     

Purification and regulation of mevalonate kinase from rat liver

Mevalonate kinase may play a key role in regulating cholesterol biosynthesis because its activity may be regulated via feedback inhibition by intermediates in the cholesterol biosynthetic pathway. To study the regulation of mevalonate kinase, the enzyme was purified to homogeneity from rat liver, and monospecific antibody against mevalonate kinase was prepared. The purified mevalonate kinase had a dimeric structure composed of identical subunits, and the Mr of the enzyme determined by gel chromatography was 86,000. Based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the subunit Mr was 39,900. The pI for mevalonate kinate was 6.2. The levels of mevalonate kinase protein and enzyme activity were determined in the livers of rats treated with either cholesterol-lowering agents (cholestyramine, pravastatin, and lovastatin) or with dietary modifications. Diets containing cholestyramine alone or cholestyramine and either pravastatin or lovastatin increased mevalonate kinase activity 3-6-fold. Mevalonate kinase activity decreased approximately 50% in rats treated with diets containing either 5% cholesterol or 5% cholesterol and 0.5% cholic acid. Fasting did not significantly change mevalonate kinase activity. The amount of mevalonate kinase protein in the liver was quantitated using immunoblots, and the changes in the levels of kinase activity induced by either drug treatment or by cholesterol feeding were correlated with similar changes in the levels of mevalonate kinase protein. Therefore, under these experimental conditions, mevalonate kinase activity in the liver was regulated principally by changes in the rates of enzyme synthesis and degradation.     

The Influence of Antimicrobial Peptides and Mucolytics on the Integrity of Biofilms Consisting of Bacteria and Yeasts as Affecting Voice Prosthetic Air Flow Resistances

The integrity of biofilms on voice prostheses used to rehabilitate speech in laryngectomized patients causes unwanted increases in airflow resistance, impeding speech. Biofilm integrity is ensured by extracellular polymeric substances (EPS). This study aimed to determine whether synthetic salivary peptides or mucolytics, including N-acetylcysteine and ascorbic acid, influence the integrity of voice prosthetic biofilms. Biofilms were grown on voice prostheses in an artificial throat model and exposed to synthetic salivary peptides, mucolytics and two different antiseptics (chlorhexidine and Triclosan). Synthetic salivary peptides did not reduce the air flow resistance of voice prostheses after biofilm formation. Although both chlorhexidine and Triclosan reduced microbial numbers on the prostheses, only the Triclosan-containing positive control reduced the air flow resistance. Unlike ascorbic acid, the mucolytic N-acetylcysteine removed most EPS from the biofilms and induced a decrease in air flow resistance.     

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.