Drosophila melanogaster spread from sub-Saharan Africa to the rest of the world colonizing new environments. Here, we modeled the joint demography of African (Zimbabwe), European (The Netherlands), and North American (North Carolina) populations using an approximate Bayesian computation (ABC) approach. By testing different models (including scenarios with continuous migration), we found that admixture between Africa and Europe most likely generated the North American population, with an estimated proportion of African ancestry of 15%. We also revisited the demography of the ancestral population (Africa) and found-in contrast to previous work-that a bottleneck fits the history of the population of Zimbabwe better than expansion. Finally, we compared the site-frequency spectrum of the ancestral population to analytical predictions under the estimated bottleneck model. TO date, several studies have confirmed that Drosophila melanogaster originated in sub-Saharan Africa and spread to the rest of the world (Lachaise et al. 1988;David and Capy 1988;Begun and Aquadro 1993; Andolfatto 2001;Stephan and Li 2007). With its cosmopolitan distribution we expect that different populations have evolved and adapted differently to distinct environments, making D. melanogaster a perfect study system for both adaptation and population history. Extensive research has been performed to detect signatures of adaptation at the genome level (Sabeti et al. 2006;Li and Stephan 2006;Zayed and Whitfield 2008). Such detection usually depends on the underlying demographic scenario, since demographic events can leave similar patterns on the genome as adaptive (selective) events (Kim and Stephan 2002;Glinka et al. 2003;Jensen et al. 2005;Nielsen et al. 2005;Pavlidis et al. 2008Pavlidis et al. , 2010a. Therefore, a better understanding of the demography of a population will not only allow us to estimate past and present population sizes and the times of the population size changes but will also decrease the rate of false positives of signatures of adaptation. Here we study the demography of African, European, and North American populations, with an emphasis on the North American population.There is evidence that D. melanogaster colonized North America ,200 years ago (Johnson 1913;Sturtevant 1920;Keller 2007). D. melanogaster (then known as D. ampelophila) was first reported in New York in 1875 by New York State entomologist Lintner (Lintner 1882;Keller 2007). In the year 1879 several articles were published indicating the appearance of D. melanogaster in several parts of eastern North America, including Connecticut and Massachusetts (Johnson 1913). At that time the dipteran fauna was very well described. It is therefore unlikely that entomologists would have overlooked D. melanogaster for long (Keller 2007). Less than 25 years after its introduction, D. melanogaster became the most common dipteran species in North America (Howard 1900). Johnson (1913) suggested that North America could have been colonized from the tropics, since the fir...

Over 90% of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) harbor somatic mutations in myeloid-related genes, but still, current diagnostic criteria do not include molecular data. We performed genome-wide sequencing techniques to characterize the mutational landscape of a large and clinically well-characterized cohort including 367 adult MDS/MPN: chronic myelomonocytic leukemia (CMML, n=119), atypical chronic myeloid leukemia (aCML, n=71), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T, n=71) and MDS/MPN unclassifiable (MDS/MPN-U, n=106). A total of 30 genes were recurrently mutated in ≥3% of the cohort. Distribution of recurrently mutated genes and clonal architecture differed among MDS/MPN subtypes. Statistical analysis revealed significant correlations between recurrently mutated genes, as well as genotype-phenotype associations. We identified specific gene combinations that associated with distinct MDS/MPN subtypes and that were mutually exclusive with most of the other MDS/MPN (e.g. TET2-SRSF2 in CMML, ASXL1-SETBP1 in aCML or SF3B1-JAK2 in MDS/MPN-RS-T). Patients with MDS/MPN-U were the most heterogeneous and displayed different molecular profiles that mimicked the ones observed in other MDS/MPN subtypes and that had an impact on the outcome of the patients. Specific gene mutations also had an impact on the outcome of the different MDS/MPN, which may be relevant for clinical decision-making. Overall, the results of this study help to elucidate the heterogeneity found in these neoplasms, which can be of use in the clinical setting of MDS/MPN.

It has been hypothesized that the ratio of X-linked to autosomal sequence diversity is influenced by unequal sex ratios in Drosophila melanogaster populations. We conducted a genome scan of single nucleotide polymorphism (SNP) of 378 autosomal loci in a derived European population and of a subset of 53 loci in an ancestral African population. On the basis of these data and our already available X-linked data, we used a coalescent-based maximum-likelihood method to estimate sex ratios and demographic histories simultaneously for both populations. We confirm our previous findings that the African population experienced a population size expansion while the European population suffered a population size bottleneck. Our analysis also indicates that the female population size in Africa is larger than or equal to the male population size. In contrast, the European population shows a huge excess of males. This unequal sex ratio and the bottleneck alone, however, cannot account for the overly strong decrease of X-linked diversity in the European population (compared to the reduction on the autosome). The patterns of the frequency spectrum and the levels of linkage disequilibrium observed in Europe suggest that, in addition, positive selection must have acted in the derived population. I N recent years genomic scans of DNA sequence variation using single nucleotide polymorphisms (SNPs) have been performed for multiple species. These studies became possible by the availability of full genome sequences, and data are now available from a variety of organisms such as Drosophila melanogaster (Glinka et al. 2003;Orengo and Aguadé 2004;Ometto et al. 2005), humans (Akey et al. 2004), and Arabidopsis thaliana (Schmid et al. 2005). These data sets provide useful tools to address questions such as estimating population sizes and demographic histories of a species. One of the main conclusions of the work performed on D. melanogaster was that demographic events are major factors in shaping the patterns of DNA polymorphism (e.g., Andolfatto 2001; Glinka et al. 2003;Haddrill et al. 2005b). D. melanogaster is thought to have originated in sub-Saharan Africa and to have only relatively recently (10,000-15,000 years ago) colonized the rest of the world (David and Capy 1988;Lachaise et al. 1988). Populations that reside in the ancestral species range show signatures of population size expansion (Glinka et al. 2003;Pool and Aquadro 2006), while derived populations have polymorphism patterns compatible with population size bottlenecks (e.g., Andolfatto 2001;Glinka et al. 2003). Theoretical studies have since utilized the data obtained from genome scans to estimate the parameters of these demographic events (Haddrill et al. 2005b;Li and Stephan 2006).The aforementioned SNP-based genome scans in D. melanogaster were performed solely for noncoding regions on the X chromosome. This leaves us virtually ignorant about noncoding autosomal variation on a chromosomal scale. In general, data quantifying the amount of autosomal variation based ...

Background: Differences in levels of gene expression among individuals are an important source of phenotypic variation within populations. Recent microarray studies have revealed that expression variation is abundant in many species, including Drosophila melanogaster. However, previous expression surveys in this species generally focused on a small number of laboratory strains established from derived populations. Thus, these studies were not ideal for population genetic analyses.

BackgroundChanges in gene regulation are thought to be crucial for the adaptation of organisms to their environment. Transcriptome analyses can be used to identify candidate genes for ecological adaptation, but can be complicated by variation in gene expression between tissues, sexes, or individuals. Here we use high-throughput RNA sequencing of a single Drosophila melanogaster tissue to detect brain-specific differences in gene expression between the sexes and between two populations, one from the ancestral species range in sub-Saharan Africa and one from the recently colonized species range in Europe.ResultsRelatively few genes (<100) displayed sexually dimorphic expression in the brain, but there was an enrichment of sex-biased genes, especially male-biased genes, on the X chromosome. Over 340 genes differed in brain expression between flies from the African and European populations, with the inter-population divergence being highly correlated between males and females. The differentially expressed genes included those involved in stress response, olfaction, and detoxification. Expression differences were associated with transposable element insertions at two genes implicated in insecticide resistance (Cyp6g1 and CHKov1).ConclusionsAnalysis of the brain transcriptome revealed many genes differing in expression between populations that were not detected in previous studies using whole flies. There was little evidence for sex-specific regulatory adaptation in the brain, as most expression differences between populations were observed in both males and females. The enrichment of genes with sexually dimorphic expression on the X chromosome is consistent with dosage compensation mechanisms affecting sex-biased expression in somatic tissues.