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We investigate the dynamics of loss of favorable mutations in an asexual haploid population. In the current work, we consider homogeneous as well as spatially structured population models. We focus our analysis on statistical measurements of the probability distribution of the maximum population size N(sb) achieved by those mutations that have not reached fixation. Our results show a crossover behavior which demonstrates the occurrence of two evolutionary regimes. In the first regime, which takes place for small N(sb) , the probability distribution is described by a power law with characteristic exponent theta(d) =1.8 +/- 0.01. This power law is not influenced by the rate of beneficial mutations. The second regime, which occurs for intermediate to large values of N(sb), has a characteristic exponent theta(c) which increases as the rate...
The evolutionary advantage of sexual reproduction has been considered as one of the most pressing questions in evolutionary biology. While a pluralistic view of the evolution of sex and recombination has been suggested by some, here we take a simpler view and try to quantify the conditions under which sex can evolve given a set of minimal assumptions. Since real populations are finite and also subject to recurrent deleterious mutations, this minimal model should apply generally to all populations. We show that the maximum advantage of recombination occurs for an intermediate value of the deleterious effect of mutations. Furthermore we show that the conditions under which the biggest advantage of sex is achieved are those that produce the fastest fitness decline in the corresponding asexual population and are therefore the conditions fo...
The study of T cell positive selection in the thymus has long been focused on the
specificity of the MHC-TCR interactions, making use of genetically manipulated mice
that display TCR specificities or selecting peptides of limited diversity. However, little is
known on the role of the MHC molecules irrespective of the peptide specificity and the
implications of MHC multigenic structure in thymic positive selection have not been
addressed. Here, we investigated the effect of MHC class II genetic configuration on the
positive selection efficiency of naturally generated pre-selection repertoires in the
mouse thymus. Analysis of positively selected thymocyte populations in MHC-congenic
and -transgenic mice revealed that expression of I-E molecule in the thymic cortex
increases positive selection efficiency of CD4 cells by approxima...
We study the process of adaptation in a spatially structured asexual haploid population. The model assumes a local competition for replication, where each organism interacts only with its nearest neighbors. We observe that the substitution rate of beneficial mutations is smaller for a spatially structured population than that seen for populations without structure. The difference between structured and unstructured populations increases as the adaptive mutation rate increases. Furthermore, the substitution rate decreases as the number of neighbors for local competition is reduced. We have also studied the impact of structure on the distribution of adaptive mutations that fix during adaptation.
In standard interval mapping (IM) of quantitative trait loci (QTL), the QTL effect is described by a normal mixture
model. When this assumption of normality is violated, the most commonly adopted strategy is to use the previous model after data
transformation. However, an appropriate transformation may not exist or may be difficult to find. Also this approach can raise
interpretation issues. An interesting alternative is to consider a skew-normal mixture model in standard IM, and the resulting
method is here denoted as skew-normal IM. This flexible model that includes the usual symmetric normal distribution as a special
case is important, allowing continuous variation from normality to non-normality. In this paper we briefly introduce the main
peculiarities of the skew-normal distribution. The maximum likelihood estimates of para...
The double helix of DNA, when composed of dinucleotide purine - pyrimidine repeats, can adopt a left-handed helical structure called Z-DNA. For reasons not entirely understood, such dinucleotide repeats in genomic sequences have been associated with genomic instability leading to cancer. Adoption of the left handed conformation results in the formation of conformational junctions: a B to Z junction is formed at the boundaries of the helix, while a Z to Z junction is commonly formed in sequences where the dinucleotide repeat is interrupted by single base insertions or deletions that bring neighbouring helixes out of phase. B-Z junctions are shown to result in exposed nucleotides vulnerable to chemical or enzymatic modification.
Here we describe the 3-dimensional structure of a Z-Z junction stabilized by Zα, the Z-DNA binding domain of ...
High-throughput sequencing has opened up exciting possibilities in population and conservation genetics by enabling the assessment of genetic variation at genome-wide scales. One approach to reduce genome complexity, i.e. investigating only parts of the genome, is reduced-representation library (RRL) sequencing. Like similar approaches, RRL sequencing reduces ascertainment bias due to simultaneous discovery and genotyping of single-nucleotide polymorphisms (SNPs) and does not require reference genomes. Yet, generating such datasets remains challenging due to laboratory and bioinformatical issues. In the laboratory, current protocols require improvements with regards to sequencing homologous fragments to reduce the number of missing genotypes. From the bioinformatical perspective, the reliance of most studies on a single SNP caller disr...
Coquerel’s sifaka Propithecus coquereli has a large but highly fragmented distribution. Despite its Endangered (EN) IUCN conservation status, uncertainties persist regarding its actual distribution and its presence in forests that are thought to be part of its distribution range. We provide here the first extensive population surveys of Coquerel’s sifaka across a large number of forest fragments neighboring 27 sites of its known and expected distribution range in northwestern Madagascar, including 12 previously visited sites. During our diurnal surveys carried out in the dry seasons from 2009 to 2011 we observed the species in 26 of the 27 visited sites. Combining our results with previously published data, we propose a refined update of the species’ distribution range and identify areas to be surveyed. We also recorded the support tre...
Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E-04 < P < 7.57E-04). In contrast, three SNP alleles within the NOS2 cistroni...
Although endocrine changes are known to modulate the timing of major developmental transitions, the genetic mechanisms underlying these changes remain poorly understood. In insects, two developmental hormones, juvenile hormone (JH) and ecdysteroids, are coordinated with each other to induce developmental changes associated with metamorphosis. However, the regulation underlying the coordination of JH and ecdysteroid synthesis remains elusive. Here, we examined the function of a homolog of the vertebrate POU domain protein, Ventral veins lacking (Vvl)/Drifter, in regulating both of these hormonal pathways in the red flour beetle, Tribolium castaneum (Tenebrionidae). RNA interference-mediated silencing of vvl expression led to both precocious metamorphosis and inhibition of molting in the larva. Ectopic application of a JH analog on vvl k...
