Chromosomal speciation and molecular divergence--accelerated evolution in rearranged chromosomes.

Humans and their closest evolutionary relatives, the chimpanzees, differ in approximately 1.24% of their genomic DNA sequences. The fraction of these changes accumulated during the speciation processes that have separated the two lineages may be of special relevance in understanding the basis of their differences.

Associations between cytoplasmic and nuclear Loci in hybridizing populations.

We extend current multilocus models to describe the effects of migration, recombination, selection, and nonrandom mating on sets of genes in diploids with varied modes of inheritance, allowing us to consider the patterns of nuclear and cytonuclear associations (disequilibria) under various models of migration. We show the relationship between the multilocus notation recently presented by Kirkpatrick, Johnson, and Barton (developed from previous work by Barton and Turelli) and the cytonuclear parameterization of Asmussen, Arnold, and Avise and extend this notation to describe associations between cytoplasmic elements and multiple nuclear genes. Under models with sexual symmetry, both nuclear-nuclear and cytonuclear disequilibria are equivalent.

Physiological characterization of neuropathy in Fabry's disease.

Fabry's disease is commonly associated with a painful, debilitating neuropathy. Characterization of the physiological abnormalities is an important step in evaluating response to specific therapies. Twenty-two patients with Fabry's disease, and with relatively preserved renal function, underwent conventional and near-nerve conduction studies, electromyography, sympathetic skin responses, and quantitative sensory testing (QST).

The effect of deleterious alleles on adaptation in asexual populations.

We calculate the fixation probability of a beneficial allele that arises as the result of a unique mutation in an asexual population that is subject to recurrent deleterious mutation at rate U. Our analysis is an extension of previous works, which make a biologically restrictive assumption that selection against deleterious alleles is stronger than that on the beneficial allele of interest. We show that when selection against deleterious alleles is weak, beneficial alleles that confer a selective advantage that is small relative to U have greatly reduced probabilities of fixation.

General models of multilocus evolution.

In 1991, Barton and Turelli developed recursions to describe the evolution of multilocus systems under arbitrary forms of selection. This article generalizes their approach to allow for arbitrary modes of inheritance, including diploidy, polyploidy, sex linkage, cytoplasmic inheritance, and genomic imprinting. The framework is also extended to allow for other deterministic evolutionary forces, including migration and mutation.

Extending the coalescent to multilocus systems: the case of balancing selection.

Natural populations are structured spatially into local populations and genetically into diverse 'genetic backgrounds' defined by different combinations of selected alleles. If selection maintains genetic backgrounds at constant frequency then neutral diversity is enhanced. By contrast, if background frequencies fluctuate then diversity is reduced.

The effects of multilocus balancing selection on neutral variability.

We studied the effect of multilocus balancing selection on neutral nucleotide variability at linked sites by simulating a model where diallelic polymorphisms are maintained at an arbitrary number of selected loci by means of symmetric overdominance. Different combinations of alleles define different genetic backgrounds that subdivide the population and strongly affect variability. Several multilocus fitness regimes with different degrees of epistasis and gametic disequilibrium are allowed.

Decreased bone density in splenectomized Gaucher patients receiving enzyme replacement therapy.

Little is known about the effect of enzyme replacement therapy (ERT) on the bone abnormalities in Gaucher disease. Splenectomized Gaucher patients tend to suffer the most severe skeletal complications. We hypothesized that vitamin D supplementation would act synergistically with glucocerebrosidase infusions to increase bone density in splenectomized Gaucher patients.

Neutral evolution in spatially continuous populations.

We introduce a general recursion for the probability of identity in state of two individuals sampled from a population subject to mutation, migration, and random drift in a two-dimensional continuum. The recursion allows for the interactions induced by density-dependent regulation of the population, which are inevitable in a continuous population. We give explicit series expansions for large neighbourhood size and for low mutation rates respectively and investigate the accuracy of the classical Malécot formula for these general models.

The treatment of dorsal fracture-dislocation of the proximal interphalangeal joint by closed reduction and Kirschner wire fixation: a 16-year follow up.

Ten patients who had sustained 11 unstable dorsal fracture-dislocations of finger proximal interphalangeal joints were reviewed at a mean follow-up of 16 years. All had been treated acutely by closed reduction and transarticular Kirschner wire fixation of the proximal interphalangeal joint, without any attempt at reduction of the fracture of the base of the middle phalanx, which probably involved 30-60% of the articular surface. Seven of the ten patients complained of no finger pain or stiffness, and none complained of severe pain.

Understanding quantitative genetic variation.

Until recently, it was impracticable to identify the genes that are responsible for variation in continuous traits, or to directly observe the effects of their different alleles. Now, the abundance of genetic markers has made it possible to identify quantitative trait loci (QTL)--the regions of a chromosome or, ideally, individual sequence variants that are responsible for trait variation. What kind of QTL do we expect to find and what can our observations of QTL tell us about how organisms evolve? The key to understanding the evolutionary significance of QTL is to understand the nature of inherited variation, not in the immediate mechanistic sense of how genes influence phenotype, but, rather, to know what evolutionary forces maintain genetic variability.

Selection for recombination in small populations.

The reasons that sex and recombination are so widespread remain elusive. One popular hypothesis is that sex and recombination promote adaptation to a changing environment. The strongest evidence that increased recombination may evolve because recombination promotes adaptation comes from artificially selected populations.

Genetic variation for preadult viability in Drosophila melanogaster.

The extent of genetic variation in fitness and its components and genetic variation's dependence on environmental conditions remain key issues in evolutionary biology. We present measurements of genetic variation in preadult viability in a laboratory-adapted population of Drosophila melanogaster, made at four different densities. By crossing flies heterozygous for a wild-type chromosome and one of two different balancers (TM1, TM2), we measure both heterozygous (TM1/+, TM2/+) and homozygous (+/+) viability relative to a standard genotype (TM1/TM2).

Theory and speciation.

The study of speciation has become one of the most active areas of evolutionary biology, and substantial progress has been made in documenting and understanding phenomena ranging from sympatric speciation and reinforcement to the evolutionary genetics of postzygotic isolation. This progress has been driven largely by empirical results, and most useful theoretical work has concentrated on making sense of empirical patterns. Given the complexity of speciation, mathematical theory is subordinate to verbal theory and generalizations about data.

The role of hybridization in evolution.

Hybridization may influence evolution in a variety of ways. If hybrids are less fit, the geographical range of ecologically divergent populations may be limited, and prezygotic reproductive isolation may be reinforced. If some hybrid genotypes are fitter than one or both parents, at least in some environments, then hybridization could make a positive contribution.

The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease.

Objective: To assess the long-term systemic and neurologic responses to enzyme replacement therapy (ERT) with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease.

Study Design: Patients with type 3 Gaucher's disease (n = 21), aged 8 months to 35 years, were enrolled in a prospective study. Enzyme dose was adjusted to control systemic manifestations.

Prevalence and genomic variation of Norwalk-like viruses in central Australia in 1995-1997.

Norwalk-like viruses (NLVs) have now been found to be important causes of gastroenteritis amongst infants and young children as well as older children and adults. Although detected, such viruses appeared not to be a major cause amongst infants and young children hospitalized with gastroenteritis in Alice Springs, central Australia over the period January 1995-December 1997. Nine NLV-positive cases were identified amongst stools from 360 different patients.

Ecology. The rapid origin of reproductive isolation.

Darwin's theory of evolution by natural selection has long been accepted, but it has not been clear how selection results in reproductive isolation of two populations. In an elegant Perspective, Barton discusses two reports (Higgie et al. and Hendry et al.

Genetic hitchhiking.

Selection on one or more genes inevitably perturbs other genes, even when those genes have no direct effect on fitness. This article reviews the theory of such genetic hitchhiking, concentrating on effects on neutral loci. Maynard Smith and Haigh introduced the classical case where the perturbation is due to a single favourable mutation.

Limits to natural selection.

We review the various factors that limit adaptation by natural selection. Recent discussion of constraints on selection and, conversely, of the factors that enhance "evolvability", have concentrated on the kinds of variation that can be produced. Here, we emphasise that adaptation depends on how the various evolutionary processes shape variation in populations.

Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease.

Gaucher disease is caused by a deficiency of beta-glucocerebrosidase activity. The optimum dose and frequency of enzyme replacement therapy for Gaucher patients have not been determined. We set to compare the therapeutic effects of initiating treatment with macrophage-targeted glucocerebrosidase at a high dose followed by progressive dose reductions with that produced by initial treatment at a low dose in patients with type I Gaucher disease.