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PubMed2000

Analysis of Clines with Variable Selection and Variable Migration.

We report a likelihood-based method that estimates both dispersal and natural selection using the rate of change of the shape of a cline when selection and migration are not constant through time. We have investigated the case of local adaptation of the mosquito Culex pipiens to organophosphate insecticides in the Montpellier area in France. We have analyzed the modification of the clinal patterns at two resistance loci during the period from breeding to overwintering. We show that mosquitoes migrate extensively from breeding to overwintering sites at a rate that is markedly different from previous estimates made during the breeding season only. This migration is also strongly asymmetrical, which can be explained by different geographical distributions of breeding and overwintering sites, by variation in mosquito density along the transect, or by behavioral biases. We found that the starting time of overwintering is likely to vary between northern and southern populations and that substantial fitness costs are associated with resistance alleles at the two loci during overwintering. These results illustrate how demography and adaptive microevolution can be studied using selected markers. The method provides a framework to use population genetics and statistical models to reveal ecological and evolutionary processes.

asymmetrical gene flow↗
PubMed2004

A new statistical test of fitness set data from reciprocal transplant experiments involving intermediate phenotypes.

Experimental biologists use reciprocal transplant experiments (RTEs) involving divergent forms to test hypotheses about fitness trade-offs across, and local adaptation to, native environments. Additional evolutionary hypotheses about diversifying selection, the evolution of specialization, and the coexistence of specialists and generalists are only testable when the RTE also includes intermediate (or alternatively generalist) forms. Environmental variation makes such RTEs challenging, and so strategies that increase their effectiveness are useful. Here, we focus on improvements to the efficiency of RTEs involving intermediate forms with respect to the experimental design and the analysis of the resulting data. We provide a likelihood ratio-based test that offers increased statistical power and robustness relative to another test involving nonlinear regression, when used both for simulated data sets and for data from a study of two divergent fish species and their hybrids transplanted between two lake habitats. The test can be used with unequal numbers of observations, unequal variances, and binomial-type survival data and other nonnormal data. Simulations suggest that having equal numbers of experimental units in each phenotype-environment combination is reasonable. The intentional pairing of observations between environmental conditions (by using clones, full sibs, or half-sibs) is beneficial when paired observations have fitnesses that are negatively related between conditions but is detrimental with positive relatedness. Our methods can be extended to study more than two divergent forms.

Animals↗
PubMed1990

Evolution in bacterial plasmids and levels of selection.

Gene flow between different reproductive units such as bacterial plasmids and chromosomes presents unusual problems for evolutionary analysis. Far more than in eukaryotes, reproductive advantages at several levels of selection--genes, transposons, plasmids, cells, and clones--must be considered simultaneously to understand plasmid evolution. No level consistently prevails in conflict situations, and some reproductive units carry genes that restrain their own reproduction or survival, apparently to enhance the reproduction or survival of the higher-level reproductive units that carry them. Despite gene flow between plasmids and chromosomes, genes for certain functions show strong tendencies to occur on plasmids while others consistently occur on chromosomes. Functions generally associated with plasmids are diverse, but all are useful only in locally restricted contexts; it is argued that the selective consequences of the greater horizontal (within generation) transmission of plasmids are responsible for this pattern. The tendency for prokaryote transposons, which are also horizontally mobile, to carry genes similar to those commonly on plasmids supports this argument. The apparent trends in eukaryote plasmids and transposons to lack these same characters also accords with predictions of the local adaptation hypothesis, because genes on these genetic units are generally no more horizontally mobile than chromosomal genes. There are theoretical reasons to expect that plasmid genes tend to evolve more rapidly than chromosomal genes. "The selfish interests of genes have manifestly produced 'vehicles' in the forms of organelles, cells, individuals and yet higher units. If evolution is to predict as well as describe, then selfish interests must be understood in the framework of the constraints and opportunities generated by these 'vehicles'" (Buss, 1987, p. 182).

Bacteria↗
PubMed2005

Convergent evolution and divergent selection: lizards at the White Sands ecotone.

Ecological transition zones, where organismal phenotypes result from a delicate balance between selection and migration, highlight the interplay of local adaptation and gene flow. Here, I study the response of an entire species assemblage to natural selection across a common ecotone. Three lizard species, distributed along a dramatic environmental gradient in substrate color, display convergent adaptation of blanched coloration on the gypsum dunes of White Sands National Monument. I investigate the role of gene flow in modulating phenotypic response to selection by quantifying color variation and genetic variation across the ecotone. I find species differences in degree of background matching and in genetic connectivity of populations across the ecotone. Differences among species in phenotypic response to selection scale precisely to levels of genetic isolation. Species with higher levels of gene flow across the ecotone exhibit less dramatic responses to selection. Results also reveal a strong signal of ecologically mediated divergence for White Sands lizards. For all species, phenotypic variation is better explained by habitat similarity than genetic similarity. Convergent evolution of blanched coloration at White Sands clearly reflects the action of strong divergent selection; however, adaptive response appears to be modulated by gene flow and demographic history and can be predicted by divergence-with-gene-flow models.

Animals↗
PubMed2006

Migration and the genetic covariance between habitat preference and performance.

Studies of the genetic covariance between habitat preference and performance have reported conflicting outcomes ranging from no covariance to strong covariance. The causes of this variability remain unclear. Here we show that variation in the magnitude of genetic covariance can result from variability in migration regimes. Using data from walking stick insects and a mathematical model, we find that genetic covariance within populations between host plant preference and a trait affecting performance on different hosts (cryptic color pattern) varies in magnitude predictably among populations according to migration regimes. Specifically, genetic covariance within populations is high in heterogeneous habitats where migration between populations locally adapted to different host plants generates nonrandom associations (i.e., linkage disequilibrium) between alleles at color pattern and host preference loci. Conversely, genetic covariance is low in homogeneous habitats where a single host exists and migration between hosts does not occur. Our results show that habitat structure and patterns of migration can strongly affect the evolution and variability of genetic covariance within populations.

Alleles↗
PubMed2001

An automated technique for SPECT marker-based image registration in radionuclide therapy.

An automated technique for marker-based image registration in radionuclide therapy is described. This technique is based on localization of the centroids of external markers and on establishing correspondence between the individual markers of the two studies to be registered. Localization of the centroids of markers relies on segmenting the markers using iterative thresholding. Thresholding is locally adaptive in order to account for study-dependent conditions (e.g. crossover between adjacent markers and markers with varying radioactive concentrations). Following marker segmentation, the centroids of the markers are computed based on an intensity-weighted method. Finally, prior to the least-squares fit registration, the markers of the two sets are matched to achieve one-to-one correspondence. The technique was applied to both simulated and patient studies resulting in mean residual three-dimensional registration errors (+/- 1SD) of 1.7 +/- 0.1 mm and 3.5 +/- 0.3 mm respectively. The technique was compared with a semi-automated approach and no significant difference was found between the mean residual three-dimensional registration errors (t = 0.281. p = 0.8). This automated marker-based image registration technique provides robust and accurate registration. Although it was developed as part of a programme to generate three-dimensional dose distributions for radionuclide therapy, it could be useful for other clinical applications.

Algorithms↗
PubMed2005

Comparison between Hilbert-Huang transform and scalogram methods on non-stationary biomedical signals: application to laser Doppler flowmetry recordings.

A significant transient increase in laser Doppler flowmetry (LDF) signals is observed in response to a local and progressive cutaneous pressure application on healthy subjects. This reflex may be impaired in diabetic patients. The work presents a comparison between two signal processing methods that provide a clarification of this phenomenon. Analyses by the scalogram and the Hilbert-Huang transform (HHT) of LDF signals recorded at rest and during a local and progressive cutaneous pressure application are performed on healthy and type 1 diabetic subjects. Three frequency bands, corresponding to myogenic, neurogenic and endothelial related metabolic activities, are studied at different time intervals in order to take into account the dynamics of the phenomenon. The results show that both the scalogram and the HHT methods lead to the same conclusions concerning the comparisons of the myogenic, neurogenic and endothelial related metabolic activities-during the progressive pressure and at rest-in healthy and diabetic subjects. However, the HHT shows more details that may be obscured by the scalogram. Indeed, the non-locally adaptative limitations of the scalogram can remove some definition from the data. These results may improve knowledge on the above-mentioned reflex as well as on non-stationary biomedical signal processing methods.

Algorithms↗
PubMed2026

Dissecting contributions of directional and balancing selection to trajectories of mitochondrial haplotype evolution in Drosophila melanogaster.

Emerging evidence suggests mtDNA haplotypes contribute to fitness variation and local adaptation, with directional thermal selection and negative frequency-dependent selection shaping haplotype diversity. However, their interplay remains unexplored. We conducted experimental evolution using Drosophila melanogaster populations from opposite ends of an Australian latitudinal cline (Melbourne and Townsville), exposing them to contrasting temperatures (17°C versus 27°C) and varying starting frequencies of two mtDNA haplotypes (A1 and B1) that occur at appreciable frequencies in these populations. We paired this with population genetic simulations to estimate selection and its influence on haplotype trajectories. Haplotype frequencies were influenced by interactions involving temperature, starting frequency, and nuclear genomic background (Melbourne, Townsville, or admixed). Although prior work predicted A1 should be favoured at the warmer temperature and B1 at the cooler temperature, A1 was generally favoured across both temperatures. Simulations supported directional selection in populations evolving at 17°C in the Melbourne background; otherwise dynamics were best explained by balancing selection shaped by negative frequency-dependent fitness effects. Patterns also varied across nuclear backgrounds, suggestive of mito-nuclear epistasis. These findings challenge a simple thermal adaptation model of mtDNA dynamics, suggesting that mtDNA evolution is shaped by interacting effects of temperature, frequency-dependence, nuclear background and experimental environment.

adaptation↗
PubMed1997

Polymorphism and locus-specific effects on polymorphism at microsatellite loci in natural Drosophila melanogaster populations.

We have studied the natural variation at microsatellite loci in two African and five non-African populations of Drosophila melanogaster. Ten dinucleotide simple sequence loci were cloned from chromosomally mapped P1 clones and typed for single individuals from isofemale lines of the respective populations. We find that the African populations harbor the largest degree of diversity, while the non-African populations show a lower diversity. This supports previous results that D. melanogaster originated in Africa and spread across the rest of the world in historic times. Using genetic distance measures, we find also a distinct population subdivision between the non-African populations. Most interestingly, we find for some loci in some populations a strongly reduced variability, which cannot be explained by bottleneck effects. Employing a conservative test based on the variance in repeat number, we find that at least one locus in one population deviates significantly from the expectations of mutation-drift equilibrium. We suggest that this may be due to a recent selective sweep in this chromosomal region that may have been caused by a linked locus that was involved in local adaptation of the population.

Adaptation, Physiological↗
PubMed2003

Population genetics of Caenorhabditis elegans: the paradox of low polymorphism in a widespread species.

Caenorhabditis elegans has become one of the most widely used model research organisms, yet we have little information on evolutionary processes and recent evolutionary history of this widespread species. We examined patterns of variation at 20 microsatellite loci in a sample of 23 natural isolates of C. elegans from various parts of the world. One-half of the loci were monomorphic among all strains, and overall genetic variation at microsatellite loci was low, relative to most other species. Some population structure was detected, but there was no association between the genetic and geographic distances among different natural isolates. Thus, despite the nearly worldwide occurrence of C. elegans, little evidence was found for local adaptation in strains derived from different parts of the world. The low levels of genetic variation within and among populations suggest that recent colonization and population expansion might have occurred. However, the patterns of variation are not consistent with population expansion. A possible explanation for the observed patterns is the action of background selection to reduce polymorphism, coupled with ongoing gene flow among populations worldwide.

Animals↗
PubMed1986

Age-related differences in the bone mineralization pattern of rats following exercise.

The effect of 12 weeks of treadmill exercise on the mineralization of trabecular and cortical bone was studied in rats 7, 14, and 19 months of age. Bone mineralization was evaluated by measuring concentrations of Ca, Mg, and hydroxyproline as well as uptake of 45Ca concentration in the femur, humerus, rib and calvaria. The 7- and 14-month-old rats increased mineralization in those cortical bones directly involved in exercise. The 19-month animal responded to exercise by increasing mineralization in all bones examined, including the nonweight bearing trabecular calvaria and cortical rib. From these data, it is apparent that the older animals undergo a total skeletal mineralization in response to exercise compared with local adaptation in the younger animal. Further, we provide evidence to support the use of the rat as a model in which to study mammalian bone physiology during the aging process.

Aging↗
PubMed1998

Improving the quality of private sector delivery of public health services: challenges and strategies.

Despite significant successes in controlling a number of communicable diseases in low and middle income countries, important challenges remain, one being that a large proportion of patients with conditions of public health significance, such as tuberculosis, malaria, or sexually transmitted diseases, seek care in the largely unregulated 'for profit' private sector. Private providers (PPs) often offer services which are perceived by users to be more attractive. However, the available evidence suggests that serious deficiencies in technical quality are often present. Evaluations of interventions to promote evidence-based care in high income countries have shown that multi-faceted strategies which increase provider knowledge have had some success in improving service quality. A wider range of factors needs to be considered in low and middle income countries (LMICs), especially factors which contribute to discrepancies between provider knowledge and practice. Studies have shown that PPs, especially, perceive or experience patient and community pressures to provide inappropriate treatments. LMIC governments also lack the capacity to enforce regulatory controls. Context-specific multi-faceted strategies are needed, including the local adaptation and dissemination to providers of relevant evidence, the education of patients and communities to adopt effective treatment-seeking and treatment-taking behaviour, and feasible mechanisms for ensuring and monitoring service quality, which may include a role for self-regulation by provider organizations or provider accreditation. Developing, implementing and evaluating strategies to improve the quality of service provision will depend on the involvement of the key stakeholders, including policy makers and PPs. Focusing on studies from Asia, Africa and Latin America, this paper develops a model for identifying the influences on PPs, mainly private medical practitioners, in their management of conditions of public health significance. Based on this, multi-faceted strategies for improving the quality of treatment provision are suggested. Interventions need to be inexpensive, practical, efficient, effective and sustainable over the medium to long term. Achieving this is a significant challenge.

Developing Countries↗
PubMed2026

The value of structural variants to conservation genomics in the pangenome era.

Structural variants (SVs) comprise an axis of genetic diversity with strong consequences for phenotype and fitness, making them a potentially important target for conservation genomics. Here, we review how and why SVs can play a role in conservation genomics; the different types of SVs and how they can affect phenotype; and how pangenomes and long-read sequencing are illuminating their evolution in populations, including small populations and those of conservation concern. SVs comprise multinucleotide mutations including insertions, deletions, transpositions, inversions, and other multinucleotide mutations, often overlapping genes and other functional genome regions. As a result, SVs often play important roles in phenotypic evolution and local adaptation and can contribute substantially to genetic load in inbred populations. However, our understanding of the factors influencing SV diversity in populations is still in its infancy and is complicated by the vast range of sizes, effects, and mechanisms of formation of these mutations. We argue that SVs are an important axis of genetic diversity which should be characterized alongside more traditional metrics of genetic diversity in conservation contexts. There are a number of analytical challenges to detecting and studying SVs, but analyses aimed at understanding the role of SVs in inbreeding load and population health are rapidly becoming realizable goals, accelerated by new technologies and analytical approaches. New tools, including population-scale long-read sequencing and pangenome approaches, are beginning to make SVs accessible in ways which can be readily applied in conservation settings.

Genomic Structural Variation↗
PubMed2026

Reference genomes of Japanese raccoon dog (Nyctereutes viverrinus) and a Japanese red fox (Vulpes vulpes japonica).

We established primary fibroblast cultures from a Japanese raccoon dog (Nyctereutes viverrinus) and a Japanese red fox (Vulpes vulpes japonica) and generated highly contiguous reference genome assemblies using Oxford Nanopore Technologies PromethION long-read sequencing. The Japanese raccoon dog assembly spanned 2.69 Gb in 813 scaffolds, with a scaffold N50 of 52 Mb and a Benchmarking Universal Single-Copy Orthologs (BUSCO) completeness score of 98.2%. The Japanese red fox assembly spanned 2.47 Gb in 903 scaffolds, with a scaffold N50 of 139 Mb and a BUSCO completeness score of 97.5%. Phylogenomic analysis placed the Japanese raccoon dog in a lineage distinct from the continental raccoon dog, supporting its evolutionary differentiation within Nyctereutes. The Japanese red fox formed a distinct lineage within the red fox clade, consistent with its recognized regional differentiation. These genome assemblies and associated fibroblast cultures provide resources for studies of canid systematics, population history, local adaptation, comparative genome evolution, and conservation genetics.

Canidae↗
PubMed2006

Population differentiation and the effects of herbivory and sand compaction on the subterranean growth of a desert lily.

Differences in level of herbivory can select for local adaptation and genetic differentiation of plant populations in different environments. Mean bulb depth of the desert lily Pancratium sickenbergeri, differs considerably among populations differing in the level of herbivory by the dorcas gazelle. The gazelle digs in the sand to remove most of the bulb of the lily. Deeper bulbs have less material removed by herbivory than shallow bulbs and have higher fitness. A possible confounding factor is the degree of sand compaction, which may retard the downward growth of the bulb. We conducted a common garden experiment with 2 sand types with seeds from source populations with different levels of herbivory. There was a large genetic difference among populations. Two of 3 analyses indicated that there was an interaction between population and sand type, indicating that there is a heritable component of plasticity.

Animals↗
PubMed2025

Tales of a Super Butterfly: Is Vanessa carye a Truly Migrant Species? Unraveling Migration Using Morphological and Genomics Approaches.

Among movement strategies, migratory behavior is particularly intriguing in insects. Home-breeding is often permanent, and return journeys can take several generations. Although migration is crucial to the ecological and evolutionary processes of the species involved, knowledge of insect migratory behavior needs to be better understood. Vanessa carye, a butterfly native to South America with a latitudinal range of ∼7,000 km, exemplifies this problem. This study analyzed samples collected across the species' range using single-nucleotide polymorphisms (SNPs) to assess population structure, genetic diversity, and geometric morphometrics to examine wing shape variation. Results indicate that V. carye forms a genetically homogeneous unit composed of only two potential populations spanning ∼5,000 km, geographically correlated with the Pacific Ocean and the Andes, maintaining constant gene flow, and with a mean heterozygosity of 5.74% (SE: ±0.048%). Geometric morphometrics detected no geographic differentiation in wing shapes and sizes across ∼7,000 km, suggesting an absence of local adaptation and indicating a conserved wing shape adapted to flight throughout the species' range. Our findings support V. carye as a migratory species with the longest migratory journey among American butterflies, revealing two migratory routes. With these approaches, we provide a consistent methodological framework for migratory studies in species with important gaps in knowledge of their natural history.

Animals↗
PubMed2004

Identifying signatures of selection at the enhancer of split neurogenic gene complex in Drosophila.

The Enhancer of split gene complex (E(spl)-C) is one of the more highly annotated gene regions in Drosophila, and the 12 genes within the complex help determine the spacing and patterning of adult bristles. Any E(spl)-C coding, transcribed, or cis-regulatory regions experiencing nonneutral evolution are strong candidates to harbor polymorphisms contributing to naturally occurring variation in bristle number. We confirm that the E(spl)-C is strongly conserved and show that 74% of regulatory elements previously identified in D. melanogaster are conserved in D. pseudoobscura. Regulatory elements in enhancer regions show lower nucleotide diversity and more rare polymorphisms compared with adjacent nonregulatory DNA, suggesting they are under purifying selection, and these effects are particularly pronounced when considering only conserved regulatory elements. The ratio of polymorphism to divergence was significantly different between binding sites and nonbinding sites for transcription factors within enhancer regions, suggesting the action of some form of selection. Too few polymorphisms in regions of the 3' UTR harboring regulatory motifs prevents adequate comparison of diversity and the polymorphism frequency spectrum between 3' UTR motif and nonmotif sequence. We identified at least two broad regions of the gene complex showing strong population subdivision among four populations, which is suggestive of local adaptation or background selection. Finally, two regions of the E(spl)-C exhibit low nucleotide diversity, a high level of rare polymorphisms, and an increase in linkage disequilibrium, which together suggest the action of positive selection. Notably, the gene m2 shows a significant deviation from neutrality by the McDonald-Kreitman test and resides in one of the two regions putatively experiencing a selective sweep. All sites in regions apparently visible to various selective forces are candidates for future work to determine their phenotypic effects.

3' Untranslated Regions↗
PubMed2003

Decision analysis to guide choice of interventions to reduce mother-to-child transmission of HIV.

INTRODUCTION: Antiretroviral prophylaxis, avoidance of breastfeeding, and early weaning are candidates to prevent mother-to-child transmission (MTCT) of HIV worldwide. METHODS: We developed a model to help guide population-level decisions about MTCT intervention strategies. We estimated the numbers of early childhood deaths prevented by (1) prenatal short-course zidovudine, (2) intrapartum and neonatal short-course nevirapine, (3) avoidance of breastfeeding, and (4) early weaning (age 6 months); four combinations of these; and one possible future strategy (postnatal antiretroviral prophylaxis) in a scenario typical of a developing country. We evaluated the effectiveness of the interventions for a range of R, the relative risk of mortality for children exposed to breastfeeding interventions compared with breastfed children (independent of HIV infection). We also estimated the reduction in breastfeeding transmission needed for a postnatal antiretroviral intervention to prevent more early childhood deaths than do currently available interventions. RESULTS: Where R < or = 1.5, strategies combining antiretroviral prophylaxis with breastfeeding interventions prevent the most early childhood deaths. However, strategies that include early weaning and avoidance of breastfeeding, respectively, can result in more deaths than with no intervention when R > 1.5 and R > 1.9, respectively. The relative effectiveness of a postnatal antiretroviral intervention compared with avoidance of breastfeeding varies with R; such that an intervention would be more effective than early weaning as a single intervention, at any R, if it reduced HIV transmission through breastfeeding by 25%. CONCLUSION: This spreadsheet model is a simple, locally adaptable tool to allow decision-makers to explore key questions about intervention strategies to prevent MTCT of HIV.

Anti-Retroviral Agents↗