Combining the analyses of introgressive hybridisation and linkage mapping to investigate the genetic architecture of population divergence in the lake whitefish (Coregonus clupeaformis, Mitchill)

Adaptation and reproductive isolation, the engines of biological diversity, are still elusive when discussing the genetic bases of speciation. Namely, the number of genes and magnitude of selection acting positively or negatively on genomic traits implicated in speciation is contentious. Here, we describe the first steps of an ongoing research program aimed at understanding the genetic bases of population divergence and reproductive isolation in the lake whitefish (Coregonus clupeaformis). A preliminary linkage map originating from a hybrid cross between dwarf and normal ecotypes is presented, whereby some of the segregating AFLP markers were found to be conserved among natural populations. Maximum-likelihood was used to estimate hybrid indices from non-diagnostic markers at 998 AFLP loci. This allowed identification of the most likely candidate loci that have been under the influence of selection during the natural hybridisation of whitefish originating from different glacial races. As some of these loci could be identified on the linkage map, the possibility that selection of traits in natural populations may eventually be correlated to specific chromosomal regions was demonstrated. The future prospects and potential of these approaches to elucidate the genetic bases of adaptation and reproductive isolation among sympatric ecotypes of lake whitefish is discussed.

Spatial structure and habitat variation in a grasshopper hybrid zone

A hybrid zone between the grasshoppers Chorthippus brunneus and C. jacobsi (Orthoptera: Acrididae) in northern Spain has been analyzed for variation in morphology and ecology. These species are readily distinguished by the number of stridulatory pegs on the hind femur. Both sexes are fully winged and inhabit disturbed habitats throughout the study area. We develop a maximum-likelihood approach to fitting a two-dimensional cline to geographical variation in quantitative traits and for estimating associations of population mean with local habitat. This method reveals a cline in peg number approximately 30 km south of the Picos de Europa Mountains that shows substantial deviations in population mean compared with the expectations of simple tension zone models. The inclusion of variation in local vegetation in the model explains a significant proportion of the residual variation in peg number, indicating that habitat-genotype associations contribute to the observed spatial pattern. However, this association is weak, and a number of populations continue to show strong deviations in mean even after habitat is included in the final model. These outliers may be the result of long-distance colonization of sites distant from the cline center or may be due to a patchy pattern of initial contact during postglacial expansion. As well as contrasting with the smooth hybrid zones described for Chorthippus parallelus, this situation also contrasts with the mosaic hybrid zones observed in Gryllus crickets and in parts of the hybrid zone between Bombina toad species, where habitat-genotype associations account for substantial amounts of among-site variation.

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.

Factors affecting cane yield and commercial cane sugar in the Tully district

The Tully Sugar Mill has collected information about sugarcane supplied for crushing from every block in the mill district from 1970 to 1999. Data from 1988 to 1999 were analysed to understand the extent of the variation in cane yield per hectare and commercial cane sugar in the Tully mill area. The key factors influencing the variation in cane yield and commercial cane sugar in this commercial environment were identified and the variance components computed using a restricted maximum likelihood methodology. Cane yield was predominantly influenced by the year in which it was harvested, the month when the crop was ratooned (month of harvest in the previous year) and the farm of origin. These variables were relatively more important than variety, age of crop or crop class (plant crop, first ratoon through to fourth or older ratoons) and fallowing practice (fallow or ploughout-replant). The month-of-ratooning effect was relatively stable from year-to-year. Commercial cane sugar was influenced by the year of harvest, the month of harvest and their interaction, in that the influence of the month of harvest varied from year to year. Variety and farm differences were also significant but accounted for a much lower portion of the variation in commercial cane sugar. An empirical model was constructed from the key factors that influenced commercial cane sugar and cane yield to quantify their combined influence on sugar yield (t/ha). This may be used to assist mill personnel to predict their activities more accurately, for example to calculate the impact of a late finish to the current harvest season on the following year's crop.

Using crop simulation to generate genotype by environment interaction effects for sorghum in water-limited environments

Multi-environment trials (METs) used to evaluate breeding lines vary in the number of years that they sample. We used a cropping systems model to simulate the target population of environments (TPE) for 6 locations over 108 years for 54 'near-isolines' of sorghum in north-eastern Australia. For a single reference genotype, each of 547 trials was clustered into 1 of 3 'drought environment types' (DETs) based on a seasonal water stress index. Within sequential METs of 2 years duration, the frequencies of these drought patterns often differed substantially from those derived for the entire TPE. This was reflected in variation in the mean yield of the reference genotype. For the TPE and for 2-year METs, restricted maximum likelihood methods were used to estimate components of genotypic and genotype by environment variance. These also varied substantially, although not in direct correlation with frequency of occurrence of different DETs over a 2-year period. Combined analysis over different numbers of seasons demonstrated the expected improvement in the correlation between MET estimates of genotype performance and the overall genotype averages as the number of seasons in the MET was increased.

Population pharmacokinetics of tacrolimus in adult kidney transplant recipients

Objectives: The aims of this study were to investigate the population pharmacokinetics of tacrolimus in adult kidney transplant recipients and to identify factors that explain variability. Methods: Population analysis was performed on retrospective data from 70 patients who received oral tacrolimus twice daily. Morning blood trough concentrations were measured by liquid chromatography-tandem mass spectrometry. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F), with the use of NONMEM (GloboMax LLC, Hanover, Md). Factors screened for influence on these parameters were weight, age, gender, postoperative day, days of tacrolimus therapy, liver function tests, creatinine clearance, hematocrit fraction, corticosteroid dose, and potential interacting drugs. Results. CL/F was greater in patients with abnormally low hematocrit fraction (data from 21 patients only), and it decreased with increasing days of therapy and AST concentrations (P

Modelling High-Dimensional Data by Mixtures of Factor Analyzers

We focus on mixtures of factor analyzers from the perspective of a method for model-based density estimation from high-dimensional data, and hence for the clustering of such data. This approach enables a normal mixture model to be fitted to a sample of n data points of dimension p, where p is large relative to n. The number of free parameters is controlled through the dimension of the latent factor space. By working in this reduced space, it allows a model for each component-covariance matrix with complexity lying between that of the isotropic and full covariance structure models. We shall illustrate the use of mixtures of factor analyzers in a practical example that considers the clustering of cell lines on the basis of gene expressions from microarray experiments. (C) 2002 Elsevier Science B.V. All rights reserved.

Indirect evidence of density-dependent population regulation in Aponomma hydrosauri (Acari : Ixodidae), an ectoparasite of reptiles

The extent to which density-dependent processes regulate natural populations is the subject of an ongoing debate. We contribute evidence to this debate showing that density-dependent processes influence the population dynamics of the ectoparasite Aponomma hydrosauri (Acari: Ixodidae), a tick species that infests reptiles in Australia. The first piece of evidence comes from an unusually long-term dataset on the distribution of ticks among individual hosts. If density-dependent processes are influencing either host mortality or vital rates of the parasite population, and those distributions can be approximated with negative binomial distributions, then general host-parasite models predict that the aggregation coefficient of the parasite distribution will increase with the average intensity of infections. We fit negative binomial distributions to the frequency distributions of ticks on hosts, and find that the estimated aggregation coefficient k increases with increasing average tick density. This pattern indirectly implies that one or more vital rates of the tick population must be changing with increasing tick density, because mortality rates of the tick's main host, the sleepy lizard, Tiliqua rugosa, are unaffected by changes in tick burdens. Our second piece of evidence is a re-analysis of experimental data on the attachment success of individual ticks to lizard hosts using generalized linear modelling. The probability of successful engorgement decreases with increasing numbers of ticks attached to a host. This is direct evidence of a density-dependent process that could lead to an increase in the aggregation coefficient of tick distributions described earlier. The population-scale increase in the aggregation coefficient is indirect evidence of a density-dependent process or processes sufficiently strong to produce a population-wide pattern, and thus also likely to influence population regulation. The direct observation of a density-dependent process is evidence of at least part of the responsible mechanism.

Study of n-fold Weibull competing risk model

This paper deals with an n-fold Weibull competing risk model. A characterisation of the WPP plot is given along with estimation of model parameters when modelling a given data set. These are illustrated through two examples. A study of the different possible shapes for the density and failure rate functions is also presented. (C) 2003 Elsevier Ltd. All rights reserved.

Special twin environments, genetic influences and their effects on the handedness of twins and their siblings

It has been suggested that twinning may influence handedness through the effects of birth order, intra-uterine crowding and mirror imaging. The influence of these effects on handedness (for writing and throwing) was examined in 3657 Monozygotic (MZ) and 3762 Dizygotic (DZ) twin pairs (born 1893-1992). Maximum likelihood analyses revealed no effects of birth order on the incidence of left-handedness. Twins were no more likely to be left-handed than their singleton siblings (n = 1757), and there were no differences between the DZ co-twin and sibling-twin covariances, suggesting that neither intra-uterine crowding nor the experience of being a twin affects handedness. There was no evidence of mirror imaging; the co-twin correlations of monochorionic and dichorionic MZ twins did not differ. Univariate genetic analyses revealed common environmental factors to be the most parsimonious explanation of familial aggregation for the writing-hand measure, while additive genetic influences provided a better interpretation of the throwing hand data.