The evolution of prezygotic reproductive isolation in the Drosophila pseudoobscura subgroup

Newly forming species that have differentiated in allopatry may evolve numerous barriers that prevent the interbreeding when they come back into contact with each other. The objective of this dissertation is to evaluate some mechanisms of prezygotic reproductive isolation in the D. pseudoobscura subgroup. I begin by evaluating how the evolution of female preferences and male sexual characters lead to reinforcement between Drosophila pseudoobscura and its congener D. persimils. In particular, I will evaluate two alternative hypotheses; Preference Evolution and Discrimination Enhancement, to determine how selection reduces hybridization between these sister species. Both hypotheses predict a reduction in the overlap of male traits and female preferences in hybridizing populations; however, the target of selection differs between the two. Next, I will discuss reproductive isolation as a result of competiton between gametes, in particular conspecific sperm precedence. Until this study, patterns of sperm precedence had rarely been examined between divergent populations or subspecies within a species. I will evaluate conspecific sperm precedence and its role in reproductive isolation between two subspecies: Drosophila pseudoobscura pseudoobscura and D. p. bogotana. The final portion of this dissertation examines the rapid evolution of some proteins potentially tied to the evolution of reproductive isolation. I focus on some seminal fluid proteins that may play a role in the reproductive isolation of Drsosphila species. In particular, I examine the rapid evolution of accessory gland proteins in the D. pseudoobscura subgroup by looking for the signature of positive selection in the genes that encode them. I will also evaluate the roles of insertion / deletion mutations in the evolution of these proteins. Together, the chapters of this dissertation contribute to the understanding of three forms of prezygotic reproductive isolation and their roles in speciation

Positive selection on nucleotide substitutions and indels in accessory gland proteins of the Drosophila pseudoobscura subgroup

Genes encoding reproductive proteins often diverge rapidly due to positive selection on nucleotide substitutions. While this general pattern is well established, the extent to which specific reproductive genes experience similar selection in different clades has been little explored, nor have possible targets of positive selection other than nucleotide substitutions, such as indels, received much attention. Here, we inspect for the signature of positive selection in the genes encoding five accessory gland proteins (Acps) (Acp26Aa, Acp32CD, Acp53Ea, Acp62F, and Acp70A) originally described from Drosophila melanogaster but with recognizable orthologues in the D. pseudoobscura subgroup. We compare patterns of selection within the D. psuedoobscura subgroup to those in the D. melanogaster subgroup. Similar patterns of positive selection were found in Acp26Aa and Acp62F in the two subgroups, while Acp53Ea and Acp70A experienced purifying selection in both subgroups. These proteins have thus remained targets for similar types of selection over long (\u3e21-MY) periods of time. We also found several indel substitutions and polymorphisms in Acp26Aa and Acp32CD. These indels occur in the same regions as positively selected nucleotide substitutions for Acp26Aa in the D. pseudoobscura subgroup but not in the D. melanogaster subgroup. Rates of indel substitution within Acp26Aa in the D. pseudoobscura subgroup were up to several times those in noncoding regions of the Drosophila genome. This suggests that indel substitutions may be under positive selection and may play a key role in the divergence of some Acps. © Springer Science+Business Media, Inc. 2006

A microsatellite linkage map of Drosophila mojavensis

BACKGROUND: Drosophila mojavensis has been a model system for genetic studies of ecological adaptation and speciation. However, despite its use for over half a century, no linkage map has been produced for this species or its close relatives. RESULTS: We have developed and mapped 90 microsatellites in D. mojavensis, and we present a detailed recombinational linkage map of 34 of these microsatellites. A slight excess of repetitive sequence was observed on the X-chromosome relative to the autosomes, and the linkage groups have a greater recombinational length than the homologous D. melanogaster chromosome arms. We also confirmed the conservation of Muller's elements in 23 sequences between D. melanogaster and D. mojavensis. CONCLUSIONS: The microsatellite primer sequences and localizations are presented here and made available to the public. This map will facilitate future quantitative trait locus mapping studies of phenotypes involved in adaptation or reproductive isolation using this species

Media Effects on Students during SARS Outbreak

A few months after the 2003 severe acute respiratory syndrome (SARS) outbreak, a sample of Canadian undergraduate university students completed a questionnaire that showed that, despite believing media coverage of the outbreak was excessive, they had little anxiety about acquiring SARS. Additionally, 69% of participants failed a SARS-specific knowledge section of the questionnaire

Impact of HIV-related stigma on treatment adherence: systematic review and meta-synthesis

Introduction: Adherence to HIV antiretroviral therapy (ART) is a critical determinant of HIV-1 RNA viral suppression and health outcomes. It is generally accepted that HIV-related stigma is correlated with factors that may undermine ART adherence, but its relationship with ART adherence itself is not well established. We therefore undertook this review to systematically assess the relationship between HIV-related stigma and ART adherence. Methods: We searched nine electronic databases for published and unpublished literature, with no language restrictions. First we screened the titles and abstracts for studies that potentially contained data on ART adherence. Then we reviewed the full text of these studies to identify articles that reported data on the relationship between ART adherence and either HIV-related stigma or serostatus disclosure. We used the method of meta-synthesis to summarize the findings from the qualitative studies. Results: Our search protocol yielded 14,854 initial records. After eliminating duplicates and screening the titles and abstracts, we retrieved the full text of 960 journal articles, dissertations and unpublished conference abstracts for review. We included 75 studies conducted among 26,715 HIV-positive persons living in 32 countries worldwide, with less representation of work from Eastern Europe and Central Asia. Among the 34 qualitative studies, our meta-synthesis identified five distinct third-order labels through an inductive process that we categorized as themes and organized in a conceptual model spanning intrapersonal, interpersonal and structural levels. HIV-related stigma undermined ART adherence by compromising general psychological processes, such as adaptive coping and social support. We also identified psychological processes specific to HIV-positive persons driven by predominant stigmatizing attitudes and which undermined adherence, such as internalized stigma and concealment. Adaptive coping and social support were critical determinants of participants’ ability to overcome the structural and economic barriers associated with poverty in order to successfully adhere to ART. Among the 41 quantitative studies, 24 of 33 cross-sectional studies (71%) reported a positive finding between HIV stigma and ART non-adherence, while 6 of 7 longitudinal studies (86%) reported a null finding (Pearson's χ 2=7.7; p=0.005). Conclusions: We found that HIV-related stigma compromised participants’ abilities to successfully adhere to ART. Interventions to reduce stigma should target multiple levels of influence (intrapersonal, interpersonal and structural) in order to have maximum effectiveness on improving ART adherence

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Classic and Overlap Chronic Graft-versus-Host Disease (cGVHD) Is Associated with Superior Outcome after Extracorporeal Photopheresis (ECP)

The National Institutes of Health (NIH) classification of graft-versus-host disease (GVHD) is a significant improvement over prior classifications, and has prognostic implications. We hypothesized that the NIH classification of GVHD would predict the survival of patients with GVHD treated with extracorporeal photopheresis (ECP). Sixty-four patients with steroid refractory/dependent GVHD treated with ECP were studied. The 3-year overall survival (OS) was 36% (95% confidence interval [CI] 13-59). Progressive GVHD was seen in 39% of patients with any acute GVHD (aGVHD) (classic acute, recurrent acute, overlap) compared to 3% of patients with classic chronic GVHD (cGVHD) (P=.002). OS was superior for patients with classic cGVHD (median survival, not reached) compared to overlap GVHD (median survival, 395 days, 95% CI 101 to not reached) and aGVHD (delayed, recurrent or persistent) (median survival, 72 days, 95% CI 39-152). In univariate analyses, significant predictors of survival after ECP included GVHD subtype, bilirubin, platelet count, and steroid dose. In multivariate analyses overlap plus classic cGVHD was an independent prognostic feature predictive of superior survival (hazard ratio [HR] 0.34, 95% CI 0.14-0.8, p=.014). This study suggests that NIH classification can predict outcome after ECP for steroid refractory/dependent GVHD

Incidence and outcome of chronic graft-versus-host disease using National Institutes of Health consensus criteria

Chronic graft-versus-host disease (cGVHD), a common complication after stem cell transplant (SCT), has an impact on morbidity and survival. Previous classification of cGVHD has not been reproducible or prognostic for nonrelapse mortality (NRM). Recently the National Institutes of Health (NIH) consensus criteria were proposed, but the ability of this classification to predict outcome of various subtypes of cGVHD is unknown. Patients (N = 110) undergoing an SCT for a hematologic malignancy and surviving until day 100 posttransplant from 2001 to 2003 were studied. The overall survival (OS) using a landmark analysis at day 100 was 44% versus 66% (no GVHD vs. GVHD, P = .026). The OS of patients with various types of GVHD as proposed by the NIH criteria were significantly different (P < .0001). In a univariate analyses, this was more apparent when patients with any acute features of GVHD were compared to classic cGVHD (3-year OS 46% vs. 68%, P = .033). The 3-year NRM for the entire cohort was 21%, and was not affected by presence or absence of GVHD or subtypes of GVHD. In a multivariable analysis, extensive cGVHD (hazard ratio [HR] 0.35, P = .015) and having any acute feature of GVHD after day 100 (HR 3.36, P = .0144) were significant independent predictors of survival. The OS with different NIH subtypes of GVHD after day 100 from SCT varies, and is superior for patients with classic cGVHD