Genetic Covariation between Serum {gamma}-Glutamyltransferase Activity and Cardiovascular Risk Factors

Background: Several studies have shown that variation in serum gamma-glutamyltransferase (GGT) in the population is associated with risk of death or development of cardiovascular disease, type 2 diabetes, stroke, or hypertension. This association is only partly explained by associations between GGT and recognized risk factors. Our aim was to estimate the relative importance of genetic and environmental sources of variation in GGT as well as genetic and environmental sources of covariation between GGT and other liver enzymes and markers of cardiovascular risk in adult twin pairs. Methods: We recruited 1134 men and 2241 women through the Australian Twin Registry. Data were collected through mailed questionnaires, telephone interviews, and by analysis of blood samples. Sources of variation in GGT, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and of covariation between GGT and cardiovascular risk factors were assessed by maximum-likelihood model-fitting. Results: Serum GGT, ALT, and AST were affected by additive genetic and nonshared environmental factors, with heritabilities estimated at 0.52, 0.48, and 0.32, respectively. One-half of the genetic variance in GGT was shared with ALT, AST, or both. There were highly significant correlations between GGT and body mass index; serum lipids, lipoproteins, glucose, and insulin; and blood pressure. These correlations were more attributable to genes that affect both GGT and known cardiovascular risk factors than to environmental factors. Conclusions: Variation in serum enzymes that reflect liver function showed significant genetic effects, and there was evidence that both genetic and environmental factors that affect these enzymes can also affect cardiovascular risk. (C) 2002 American Association for Clinical Chemistry.

Genetic and environmental contributions to cannabis dependence in a national young adult twin sample

Background. This paper examines genetic and environmental contributions to risk of cannabis dependence. Method. Symptoms of cannabis dependence and measures of social, family and individual risk factors were assessed in a sample of 6265 young adult male and female Australian twins born 1964-1971. Results. Symptoms of cannabis dependence were common: 11(.)0% of sample (15(.)1% of men and 7(.)8% of women) reported two or more symptoms of dependence. Correlates of cannabis dependence included educational attainment, exposure to parental conflict, sexual abuse, major depression, social anxiety and childhood conduct disorder. However, even after control for the effects of these factors, there was evidence of significant genetic effects on risk of cannabis dependence. Standard genetic modelling indicated that 44(.)7% (95% CI = 15-72(.)2) of the variance in liability to cannabis dependence could be accounted for by genetic factors, 20(.)1% (95 CI = 0-43(.)6) could be attributed to shared environment factors and 35(.)3% (95% CI = 26(.)4-45(.)7) could be attributed to non-shared environmental factors. However, while there was no evidence of significant gender differences in the magnitude of genetic and environmental influences, a model which assumed both genetic and shared environmental influences on risks of cannabis dependence among men and shared environmental but no genetic influences among women provided an equally good fit to the data. Conclusions. There was consistent evidence that genetic risk factors are important determinants of risk of cannabis dependence among men. However, it remains uncertain whether there are genetic influences on liability to cannabis dependence among women.

Altered shoot/root Na+ distribution and bifurcating salt sensitivity in Arabidopsis by genetic disruption of the Na+ transporter AtHKTI1

Sodium (Na+) is toxic to most plants, but the molecular mechanisms of plant Na+ uptake and distribution remain largely unknown. Here we analyze Arabidopsis lines disrupted in the Na+ transporter AtHKT1. AtHKT1 is expressed in the root stele and leaf vasculature. athkt1 null plants exhibit lower root Na+ levels and are more salt resistant than wild-type in short-term root growth assays. In shoot tissues, however, athkt1 disruption produces higher Na+ levels, and athkt1 and athktl/sos3 shoots are Na+-hypersensitive in long-term growth assays. Thus wild-type AtHKT1 controls root/shoot Na+ distribution and counteracts salt stress in leaves by reducing leaf Na+ accumulation. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Evidence for an independent radiation of endosymbiotic litostome ciliates within Australian marsupial herbivores

The recent discovery of isotrichid-like ciliates occurring as endosymbionts in macropodid marsupials posed interesting questions in regard to both their phyletic origin (all previous records confined to eutherian mammals) and their morphological evolution (Australian forms possibly representing missing links between previously described genera). The SSU rRNA gene was sequenced for three species (Dasytricha dehorityi, D. dogieli, and Batricha tasmaniensis) and aligned against representatives of all major ciliate classes. The Australian species did not group with the other isotrichid species but instead formed an independent radiation. Discrepancies between recent global phylogenies of the phylum Ciliophora were examined by manipulation of the aligned sequence data set. Sources of conflict between these studies did not stem from differences in outgroup choice or phylogenetic reconstruction methods. Differences in the application of confidence limits and primary sequence alignment have probably resulted in the reporting of spurious associations which are not supported by more conservative confidence or alignment methodology. At present, the ciliate subphylum Intramacro-nucleata is an unresolved polytomy which may be due to deficiencies in the SSU rRNA gene sequence dataset or indicate that the ciliates radiated into their extant classes by rapid burst-like evolution. (C) 2001 academic Press.

Genetic consequences of sequential founder events by an island-colonizing bird

The importance of founder events in promoting evolutionary changes on islands has been a subject of long-running controversy. Resolution of this debate has been hindered by a lack of empirical evidence from naturally founded island populations. Here we undertake a genetic analysis of a series of historically documented, natural colonization events by the silvereye species-complex (Zosterops lateralis), a group used to illustrate the process of island colonization in the original founder effect model. Our results indicate that single founder events do not affect levels of heterozygosity or allelic diversity, nor do they result in immediate genetic differentiation between populations. Instead, four to five successive founder events are required before indices of diversity and divergence approach that seen in evolutionarily old forms. A Bayesian analysis based on computer simulation allows inferences to be made on the number of effective founders and indicates that founder effects are weak because island populations are established from relatively large flocks. Indeed, statistical support for a founder event model was not significantly higher than for a gradual-drift model for all recently colonized islands. Taken together, these results suggest that single colonization events in this species complex are rarely accompanied by severe founder effects, and multiple founder events and/or long-term genetic drift have been of greater consequence for neutral genetic diversity.

A molecular phylogeny of rainbow skinks (Scincidae : Carlia): taxonomic and biogeographic implications

The phylogenetic relationships amongst 29 species of Carlia and Lygisaurus were estimated using a 726-base-pair segment of the protein-coding mitochondrial ND4 gene. Results do not support the recent resurrection of the genus Lygisaurus. Although most Lygisaurus species formed a single clade, this clade is nested within Carlia and includes Carlia parrhasius. Due to this new molecular evidence, and the paucity of diagnostic morphological characters separating the genera, Lygisaurus de Vis 1884 is re-synonymised with Carlia Gray 1845. Our analysis is also inconsistent with a previous suggestion that Lygisaurus timlowi should be removed to Menetia, a genus that is distantly related relative to outgroups used here. Intraspecific variation in Carlia is, in several instances, greater than interspecific distance. The most strikingly divergent lineages are found within C. rubrigularis, which appears to be paraphyletic, with southern populations more closely related to C. rhomboidalis than to northern populations of C. rubrigularis. The two C. rubrigularis-C. rhomboidalis lineages form part of a major polytomy at an intermediate level of divergence. Lack of resolution at this level, however, does not appear to be due to saturation or loss of phylogenetic signal. Rather, the polytomy probably reflects a period of relatively rapid diversification that occurred sometime during the Miocene.

Identity and genetic diversity of the sorghum ergot pathogen in Australia

Sorghum ergot was first discovered in Australia in 1996. It affects seed production and grain usage in stock feed due to concerns of animal toxicity. Three species of Claviceps are known to cause ergot of sorghum with different epidemiological, animal toxicity, and management implications. Claviceps africana was identified as the causal agent but morphological differences between isolates raised the possibility of more than one species being involved. The major aim of this study was to identify the Claviceps species causing sorghum ergot and to determine the genetic diversity among isolates of the ergot pathogen from Australia and overseas. Symptom development, sequencing of the ITS1 region, and radiolabelled DNA amplification fingerprints (RAF) were used to confirm that ergot of sorghum in Australia is caused by C. africana. The morphology of sphacelia, microconidia, macroconidia, and secondary conidia of all 36 Australian isolates studied matched the description for C. africana and the DNA sequence of the ITS1 region of 2 selected Australian isolates was identical to that of C. africana. Based on RAF analysis of 110 Australian and overseas isolates of Claviceps spp., C. africana isolates could be clearly distinguished (

Characterization of mouse profilaggrin: Evidence for nuclear engulfment and translocation of the profilaggrin B-domain during epidermal differentiation

Filaggrin is a keratin filament associated protein that is expressed in granular layer keratinocytes and derived by sequential proteolysis from a polyprotein precursor termed profilaggrin. Depending on the species, each profilaggrin molecule contains between 10 and 20 filaggrin subunits organized as tandem repeats with a calcium-binding domain at the N-terminal end. We now report the characterization of the complete mouse gene. The structural organization of the mouse gene is identical to the human profilaggrin gene and consists of three exons with a 4 kb intron within the 5' noncoding region and a 1.7 kb intron separating the sequences encoding the calcium-binding EF-hand motifs. A processed pseudogene was found embedded within the second intron. The third and largest exon encodes the second EF-hand, a basic domain (designated the B-domain) followed by 12 filaggrin repeats and a unique C-terminal tail domain. A polyclonal anti-body raised against the conceptually translated sequence of the B-domain specifically stained keratohyalin granules and colocalized with a filaggrin antibody in granular layer cells. In upper granular layer cells, B-domain containing keratohyalin granules were in close apposition to the nucleus and, in some cells, appeared to be completely engulfed by the nucleus. In transition layer cells, B-domain staining was evident in the nucleus whereas filaggrin staining remained cytoplasmic. Nuclear staining of the B-domain was also observed in primary mouse keratinocytes induced to differentiate. This study has also revealed significant sequence homology between the mouse and human promoter sequences and in the calcium-binding domain but the remainder of the protein-coding region shows substantial divergence.

Global distribution and genetic discontinuities of mangroves - emerging patterns in the evolution of Rhizophora

Mangroves are often described as a group of plants with common features and common origins based mostly on their broad distributional patterns, together with an erroneous view of comparable abilities in long-distance dispersal. However, whilst mangroves have common needs to adapt to rigorous environmental constraints associated with regular seawater inundation, individual taxa have developed different strategies and characteristics. Since mangroves are a genetically diverse group of mostly flowering plants, they may also have evolved at quite different geological periods, dispersed at different rates from different locations and developed different adaptive strategies. Current distributions of individual taxa show numerous instances of unusual extant distribution which demonstrate finite dispersal limitations, especially across open water. Our preliminary assessment of broad distribution and discontinuities reveals important patterns. Discontinuities, in the absence of current dispersal barriers, may be explained by persistent past barriers. As we learn more about discontinuities, we are beginning to appreciate their immense implications and what they might tell us about past geological conditions and how these might have influenced the distribution and evolution of mangroves. In this article, we describe emerging patterns in genetic relationships and distributions based on both current knowledge and preliminary results of our studies of molecular and morphometric characteristics of Rhizophora species in the Indo West Pacific region.

Testing the relationship between morphological and molecular rates of change along phylogenies

Molecular evolution has been considered to be essentially a stochastic process, little influenced by the pace of phenotypic change. This assumption was challenged by a study that demonstrated an association between rates of morphological and molecular change estimated for total-evidence phylogenies, a finding that led some researchers to challenge molecular date estimates of major evolutionary radiations. Here we show that Omland's (1997) result is probably due to methodological bias, particularly phylogenetic nonindependence, rather than being indicative of an underlying evolutionary phenomenon. We apply three new methods specifically designed to overcome phylogenetic bias to 13 published phylogenetic datasets for vertebrate taxa, each of which includes both morphological characters and DNA sequence data. We find no evidence of an association between rates of molecular and morphological rates of change.

Empirical evidence for ultrametric structure in multi-layer perceptron error surfaces

Combinatorial optimization problems share an interesting property with spin glass systems in that their state spaces can exhibit ultrametric structure. We use sampling methods to analyse the error surfaces of feedforward multi-layer perceptron neural networks learning encoder problems. The third order statistics of these points of attraction are examined and found to be arranged in a highly ultrametric way. This is a unique result for a finite, continuous parameter space. The implications of this result are discussed.

Analysis of genetic diversity in Cassia brewsteri with randomly amplified DNA fingerprints (RAFS)

Genetic diversity in Cassia brewsteri (F. Muell.) F. Muell. ex Benth. was assessed with Randomly Amplified DNA Fingerprints (RAFs). Thirty accessions of C. brewsteri collected from throughout its natural distribution were analysed with three random decamer primers, along with three accessions of C. tomentella (Benth.) Domin and a single accession of each of C. queenslandica C. T. White and C. marksiana (F. M. Bailey) Domin. The three primers yielded a reproducible amplification profile of 265 scorable polymorphic fragments for the 35 accessions. These molecular markers were used to calculate Nei and Li similarity coefficients between each pair of individuals. A matrix of dissimilarity of each pair of individuals was examined by multidimensional scaling (MDS). The analysis supports the division of C. brewsteri into two subspecies and the suggestion that intergradation of C. brewsteri and C. tomentella can occur where the distributions of these species meet.

Analysis of genetic diversity within Australian lucerne cultivars and implications for future genetic improvement

Lucerne (Medicago sativa L.) is autotetraploid, and predominantly allogamous. This complex breeding structure maximises the genetic diversity within lucerne populations making it difficult to genetically discriminate between populations. The objective of this study was to evaluate the level of random genetic diversity within and between a selection of Australian-grown lucerne cultivars, with tetraploid M. falcata included as a possible divergent control source. This diversity was evaluated using random amplified polymorphic DNA (RAPDs). Nineteen plants from each of 10 cultivars were analysed. Using 11 RAPD primers, 96 polymorphic bands were scored as present or absent across the 190 individuals. Genetic similarity estimates (GSEs) of all pair-wise comparisons were calculated from these data. Mean GSEs within cultivars ranged from 0.43 to 0.51. Cultivar Venus (0.43) had the highest level of intra-population genetic diversity and cultivar Sequel HR (0.51) had the lowest level of intra-population genetic diversity. Mean GSEs between cultivars ranged from 0.31 to 0.49, which overlapped with values obtained for within-cultivar GSE, thus not allowing separation of the cultivars. The high level of intra- and inter-population diversity that was detected is most likely due to the breeding of synthetic cultivars using parents derived from a number of diverse sources. Cultivar-specific polymorphisms were only identified in the M. falcata source, which like M. sativa, is outcrossing and autotetraploid. From a cluster analysis and a principal components analysis, it was clear that M. falcata was distinct from the other cultivars. The results indicate that the M. falcata accession tested has not been widely used in Australian lucerne breeding programs, and offers a means of introducing new genetic diversity into the lucerne gene pool. This provides a means of maximising heterozygosity, which is essential to maximising productivity in lucerne.

Genetic variability in cultivated common bean beyond the two major gene pools

It is generally accepted that two major gene pools exist in cultivated common bean (Phaseolus vulgaris L.), a Middle American and an Andean one. Some evidence, based on unique phaseolin morphotypes and AFLP analysis, suggests that at least one more gene pool exists in cultivated common bean. To investigate this hypothesis, 1072 accessions from a common bean core collection from the primary centres of origin, held at CIAT, were investigated. Various agronomic and morphological attributes (14 categorical and 11 quantitative) were measured. Multivariate analyses, consisting of homogeneity analysis and clustering for categorical data, clustering and ordination techniques for quantitative data and nonlinear principal component analysis for mixed data, were undertaken. The results of most analyses supported the existence of the two major gene pools. However, the analysis of categorical data of protein types showed an additional minor gene pool. The minor gene pool is designated North Andean and includes phaseolin types CH, S and T; lectin types 312, Pr, B and K; and mostly A5, A6 and A4 types alpha-amylase inhibitor. Analysis of the combined categorical data of protein types and some plant categorical data also suggested that some other germplasm with C type phaseolin are distinguished from the major gene pools.

Revisiting the question of limited genetic variation within Schistosoma japonicum

Recent electrophoretic data have indicated that Schistosoma japonicum in mainland China may be a species complex, with the existence of a cryptic species being predicted from the analysis of schistosome populations from Sichuan province. To investigate the Sichuan form of S. japonicum, 4.9 kbp of mitochondrial DNA from each of three samples of the parasite from China (two from Sichuan and one from Hunan) and one from Sorsogon in the Philippines were amplified, sequenced and characterized. The sequence data were compared with those from the related South-east Asian species of S. mekongi (Khong Island, Laos) and S. malayensis (Baling, Malaysia) and that from S. japonicum from Anhui (China). At both the nucleotide and amino-acid levels, the variation among the five S. japonicum samples was limited ( < 1%). This was consistent with the conclusions drawn from previous molecular studies, in which minimal variation among S. japonicum populations was also detected. In contrast, S. mekongi and S. malayensis, species recognized as separate but closely related, differ from each other by about 10%, and each differs by 25%-26% from S. japonicum. Phylogenetic trees provided a graphic representation of these differences, showing all S. japonicum sequences to be very tightly clustered and distant from S. mekongi and S. malayensis, the last two being clearly distinct from each other. The results thus indicate no significant intraspecific genetic variation among S. japonicum samples collected from different geographical areas and do not support the idea of a distinct form in Sichuan.