Gene Flow and Selection in a Natural Population of DROSOPHILA MELANOGASTER

A marked genetic differentiation to the presence of alcohol in the environment has been shown to occur between inside cellar and adjacent outside sections of a vineyard population of D. melanogaster ( McKenzie and Parsons 1974). Estimates of migration during the vintage period suggest considerable movement occurs from outside into the cellar and that the most tolerant genotypes are the most successful migrants. A quantitative model of this system suggests that the selection intensity may not be a limiting factor in maintaining the differentiation. It also suggests that gene flow must be restricted between sections of the population at all but vintage periods if this differentiation is to persist.     

Epigenetic Drugs Can Stimulate Metastasis through Enhanced Expression of the Pro-Metastatic Ezrin Gene

Ezrin has been reported to be upregulated in many tumors and to participate in metastatic progression. No study has addressed epigenetic modification in the regulation of Ezrin gene expression, the importance of which is unknown. Here, we report that highly metastatic rhabdomyosarcoma (RMS) cells with high levels of Ezrin have elevated acetyl-H3-K9 and tri-methyl-H3-K4 as well as reduced DNA methylation at the Ezrin gene promoter. Conversely, poorly metastatic RMS cells with low levels of Ezrin have reduced acetyl-H3-K9 and elevated methylation. Thus epigenetic covalent modifications to histones within nucleosomes of the Ezrin gene promoter are linked to Ezrin expression, which in fact can be regulated by epigenetic mechanisms. Notably, treatment with histone deacetylase (HDAC) inhibitors or DNA demethylating agents could restore Ezrin expression and stimulate the metastatic potential of poorly metastatic RMS cells characterized by low Ezrin levels. However, the ability of epigenetic drugs to stimulate metastasis in RMS cells was inhibited by expression of an Ezrin-specific shRNA. Our data demonstrate the potential risk associated with clinical application of broadly acting covalent epigenetic modifiers, and highlight the value of combination therapies that include agents specifically targeting potent pro-metastatic genes.     

Population Structure and Adaptive Divergence in a High Gene Flow Marine Fish: The Small Yellow Croaker (Larimichthys polyactis)

The spatial distribution of genetic diversity has been long considered as a key component of policy development for management and conservation of marine fishes. However, unraveling the population genetic structure of migratory fish species is challenging due to high potential for gene flow. Despite the shallow population differentiation revealed by putatively neutral loci, the higher genetic differentiation with panels of putatively adaptive loci could provide greater resolution for stock identification. Here, patterns of population differentiation of small yellow croaker (Larimichthys polyactis) were investigated by genotyping 15 highly polymorphic microsatellites in 337 individuals of 15 geographic populations collected from both spawning and overwintering grounds. Outlier analyses indicated that the locus Lpol03 might be under directional selection, which showed a strong homology with Grid2 gene encoding the glutamate receptor δ2 protein (GluRδ2). Based on Lpol03, two distinct clusters were identified by both STRUCTURE and PCoA analyses, suggesting that there were two overwintering aggregations of L. polyactis. A novel migration pattern was suggested for L. polyactis, which was inconsistent with results of previous studies based on historical fishing yield statistics. These results provided new perspectives on the population genetic structure and migratory routes of L. polyactis, which could have significant implications for sustainable management and utilization of this important fishery resource.     

Pangenome Analysis of Burkholderia pseudomallei: Genome Evolution Preserves Gene Order despite High Recombination Rates

The pangenomic diversity in Burkholderia pseudomallei is high, with approximately 5.8% of the genome consisting of genomic islands. Genomic islands are known hotspots for recombination driven primarily by site-specific recombination associated with tRNAs. However, recombination rates in other portions of the genome are also high, a feature we expected to disrupt gene order. We analyzed the pangenome of 37 isolates of B. pseudomallei and demonstrate that the pangenome is ‘open’, with approximately 136 new genes identified with each new genome sequenced, and that the global core genome consists of 4568±16 homologs. Genes associated with metabolism were statistically overrepresented in the core genome, and genes associated with mobile elements, disease, and motility were primarily associated with accessory portions of the pangenome. The frequency distribution of genes present in between 1 and 37 of the genomes analyzed matches well with a model of genome evolution in which 96% of the genome has very low recombination rates but 4% of the genome recombines readily. Using homologous genes among pairs of genomes, we found that gene order was highly conserved among strains, despite the high recombination rates previously observed. High rates of gene transfer and recombination are incompatible with retaining gene order unless these processes are either highly localized to specific sites within the genome, or are characterized by symmetrical gene gain and loss. Our results demonstrate that both processes occur: localized recombination introduces many new genes at relatively few sites, and recombination throughout the genome generates the novel multi-locus sequence types previously observed while preserving gene order.     

Measuring Gene Flow among Populations Having High Levels of Genetic Fragmentation

We present an analysis of the genetic structures of 22 species of salamanders, with regard to levels of gene flow among populations. We estimate the gene flow parameter, Nm (the product of the effective population number and rate of migration among populations) using two alternative methods described by Wright and Slatkin. For most species, these two methods give approximately congruent estimates of Nm; when estimates differ, the method of Wright produces values slightly larger than those derived by the method of Slatkin. We analyze these results in light of independently derived historical inferences of the fragmentation of populations. This analysis suggests that the Nm values calculated from protein polymorphisms may contain information more relevant to historical patterns of gene exchange than to the current population dynamics; moderately large values of Nm may be calculated for species containing populations known to be no longer exchanging genes. Application of a method for estimating the maximum possible rate of gene exchange among populations indicates that, for most species studied here, gene flow among populations probably is no greater than the mutation rate. We suggest that most plethodontid species cannot be viewed as units whose cohesion is maintained by continuing gene exchange. Furthermore, we suggest that phenotypic uniformity among populations is not easily explained by hypotheses of continual stabilizing selection and propose that future work concentrate upon clarification of the genetic and epigenetic factors conferring self-maintenance or autopoietic properties on living systems.     

Hidden Historical Habitat-Linked Population Divergence and Contemporary Gene Flow of a Deep-Sea Patellogastropod Limpet

Hydrothermal vents and hydrocarbon seeps in the deep ocean are rare oases fueled by chemosynthesis. Biological communities inhabiting these ecosystems are often distributed in widely separated habitats, raising intriguing questions on how these organisms achieve connectivity and whether habitat types facilitate intraspecific divergence. The deep-sea patellogastropod limpet Bathyacmaea nipponica that colonizes both vents and seeps across ∼2,400 km in the Northwest Pacific is a feasible model to answer these questions. We analyzed 123 individuals from four vents and three seeps using a comprehensive method incorporating population genomics and physical ocean modeling. Genome survey sequencing and genotyping-by-sequencing resulted in 9,838 single-nucleotide polymorphisms for population genomic analyses. Genetic divergence and demographic analyses revealed four habitat-linked (i.e., three seep and one vent) genetic groups, with the vent genetic group established via the opportunistic invasion of a few limpet larvae from a nearby seep genetic group. TreeMix analysis uncovered three historical seep-to-vent migration events. ADMIXTURE and divMigrate analyses elucidated weak contemporary gene flow from a seep genetic group to the vent genetic group. Physical ocean modeling underlined the potential roles of seafloor topography and ocean currents in shaping the genetic connectivity, contemporary migration, and local hybridization of these deep-sea limpets. Our study highlighted the power of integrating genomic and oceanographic approaches in deciphering the demography and diversification of deep-sea organisms. Given the increasing anthropogenic activities (e.g., mining and gas hydrate extraction) affecting the deep ocean, our results have implications for the conservation of deep-sea biodiversity and establishment of marine protected areas.     

Relating Diseases by Integrating Gene Associations and Information Flow through Protein Interaction Network

Identifying similar diseases could potentially provide deeper understanding of their underlying causes, and may even hint at possible treatments. For this purpose, it is necessary to have a similarity measure that reflects the underpinning molecular interactions and biological pathways. We have thus devised a network-based measure that can partially fulfill this goal. Our method assigns weights to all proteins (and consequently their encoding genes) by using information flow from a disease to the protein interaction network and back. Similarity between two diseases is then defined as the cosine of the angle between their corresponding weight vectors. The proposed method also provides a way to suggest disease-pathway associations by using the weights assigned to the genes to perform enrichment analysis for each disease. By calculating pairwise similarities between 2534 diseases, we show that our disease similarity measure is strongly correlated with the probability of finding the diseases in the same disease family and, more importantly, sharing biological pathways. We have also compared our results to those of MimMiner, a text-mining method that assigns pairwise similarity scores to diseases. We find the results of the two methods to be complementary. It is also shown that clustering diseases based on their similarities and performing enrichment analysis for the cluster centers significantly increases the term association rate, suggesting that the cluster centers are better representatives for biological pathways than the diseases themselves. This lends support to the view that our similarity measure is a good indicator of relatedness of biological processes involved in causing the diseases. Although not needed for understanding this paper, the raw results are available for download for further study at ftp://ftp.ncbi.nlm.nih.gov/pub/qmbpmn/DiseaseRelations/.     

High Rates of Gene Flow by Pollen and Seed in Oak Populations across Europe

Gene flow is a key factor in the evolution of species, influencing effective population size, hybridisation and local adaptation. We analysed local gene flow in eight stands of white oak (mostly Quercus petraea and Q. robur, but also Q. pubescens and Q. faginea) distributed across Europe.Adult trees within a given area in each stand were exhaustively sampled (range [239, 754], mean 423), mapped, and acorns were collected ([17,147], 51) from several mother trees ([3], [47], 23). Seedlings ([65,387], 178) were harvested and geo-referenced in six of the eight stands. Genetic information was obtained from screening distinct molecular markers spread across the genome, genotyping each tree, acorn or seedling. All samples were thus genotyped at 5–8 nuclear microsatellite loci. Fathers/parents were assigned to acorns and seedlings using likelihood methods. Mating success of male and female parents, pollen and seed dispersal curves, and also hybridisation rates were estimated in each stand and compared on a continental scale.On average, the percentage of the wind-borne pollen from outside the stand was 60%, with large variation among stands (21–88%). Mean seed immigration into the stand was 40%, a high value for oaks that are generally considered to have limited seed dispersal. However, this estimate varied greatly among stands (20–66%). Gene flow was mostly intraspecific, with large variation, as some trees and stands showed particularly high rates of hybridisation.Our results show that mating success was unevenly distributed among trees. The high levels of gene flow suggest that geographically remote oak stands are unlikely to be genetically isolated, questioning the static definition of gene reserves and seed stands.     

Dihydroactinidiolide,a High Light-Induced 13-Carotene Derivative that Can Regulate Gene Expression and Photoacclimation in Arabidopsis

Dear Editor,
The physiological functions of carotenoids in plants go beyond their traditional roles as accessory light-har- vesting pigments, natural colorants, and quenchers of tri- plet chlorophyll and singlet oxygen （102）. Recent studies have indeed emphasized the functional role of molecules derived from carotenoids as phytohormones （Ruyter-Spira et al., 20β） or messengers in stress signaling pathways （Havaux, 2014）. In particular, chemical quenching of 102 by carotenoids within the photosystems involves oxidation of the carotenoid molecules, generating a variety of oxi- dized products （Ramel et al., 2012）. β-Cyclocitral, a volatile C7 derivative of β-carotene, is one such molecule produced during high light stress, which was found to induce changes in the expression of 102-responsive genes （Ramel et al., 2012）. Moreover, the β-cyclocitral-dependent gene repro- gramming was associated with an increased tolerance of the plants to photooxidative stress. These effects appeared to be specific to β-cyclocitral since they were not observed with β-ionone, a C9-oxidized derivative of ~-carotene, which was not able to induce or repress the expression of 1O2 gene markers. Based on those results, it was pro- posed that β-cyclocitral is a plastid messenger involved in the chloroplast-to-nucleus 1O2 signaling pathway lead- ing to acclimation to high light stress （Ramel et al., 2012）. However, in vitro 102 oxidation of β-carotene is known to produce other volatile compounds besides β-cyclocitral and IB-ionone, such as dihydroactinidiolide （dhA, Figure 1A） and a-ionene （Ramel et al., 2012）. The dhA molecule is a lac- tone （cyclic ester） resulting from the secondary oxidation of β-ionone through the intermediate 5,6-epoxy-β-ionone （Havaux, 2014）. Both dhA and o-ionene were detected in plant leaves and fruits （e.g. Del Mar Caja et al., 2009; Ramel et al., 2012）. Interestingly, dhA, but not o-ionene, was reported to accumulate in Arabidopsis leaves under hiclh liclht str     

Contemporary Gene Flow is a Major Force Shaping the Aspergillus fumigatus Population in Auckland,New Zealand

Mycopathologia - Aspergillus fumigatus is a globally distributed opportunistic fungal pathogen capable of causing highly lethal invasive aspergillosis in immunocompromised individuals. Recent...     

Genetic Barriers to Historical Gene Flow between Cryptic Species of Alpine Bumblebees Revealed by Comparative Population Genomics

Evidence is accumulating that gene flow commonly occurs between recently diverged species, despite the existence of barriers to gene flow in their genomes. However, we still know little about what regions of the genome become barriers to gene flow and how such barriers form. Here, we compare genetic differentiation across the genomes of bumblebee species living in sympatry and allopatry to reveal the potential impact of gene flow during species divergence and uncover genetic barrier loci. We first compared the genomes of the alpine bumblebee Bombus sylvicola and a previously unidentified sister species living in sympatry in the Rocky Mountains, revealing prominent islands of elevated genetic divergence in the genome that colocalize with centromeres and regions of low recombination. This same pattern is observed between the genomes of another pair of closely related species living in allopatry (B. bifarius and B. vancouverensis). Strikingly however, the genomic islands exhibit significantly elevated absolute divergence (d_XY) in the sympatric, but not the allopatric, comparison indicating that they contain loci that have acted as barriers to historical gene flow in sympatry. Our results suggest that intrinsic barriers to gene flow between species may often accumulate in regions of low recombination and near centromeres through processes such as genetic hitchhiking, and that divergence in these regions is accentuated in the presence of gene flow.     

Spread of a New Parasitic B Chromosome Variant Is Facilitated by High Gene Flow

The B₂₄ chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B₂₄ frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise N_em estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B₂₄ diffusion both eastward and westward, with minor role for B₂₄ drive due to the arrival of drive suppressor genes which are also frequent in the donor population.     

Gene Flow,Recombination, and Selection in Cyanobacteria: Population Structure of Geographically Related Planktothrix Freshwater Strains

Several Planktothrix strains, each producing a distinct oligopeptide profile, have been shown to coexist within Lake Steinsfjorden (Norway). Using nonribosomal peptide synthetase (NRPS) genes as markers, it has been shown that the Planktothrix community comprises distinct genetic variants displaying differences in bloom dynamics, suggesting a Planktothrix subpopulation structure. Here, we investigate the Planktothrix variants inhabiting four lakes in southeast of Norway utilizing both NRPS and non-NRPS genes. Phylogenetic analyses showed similar topologies for both NRPS and non-NRPS genes, and the lakes appear to have similar structuring of Planktothrix genetic variants. The structure of distinct variants was also supported by very low genetic diversity within variants compared to the between-variant diversity. Incongruent topologies and split decomposition revealed recombination events between Planktothrix variants. In several strains the gene variants seem to be a result of recombination. Both NRPS and non-NRPS genes are dominated by purifying selection; however, sites subjected to positive selection were also detected. The presence of similar and well-separated Planktothrix variants with low internal genetic diversity indicates gene flow within Planktothrix populations. Further, the low genetic diversity found between lakes (similar range as within lakes) indicates gene flow also between Planktothrix populations and suggests recent, or recurrent, dispersals. Our data also indicate that recombination has resulted in new genetic variants. Stability within variants and the development of new variants are likely to be influenced by selection patterns and within-variant homologous recombination.     

Inferred vs Realized Patterns of Gene Flow: An Analysis of Population Structure in the Andros Island Rock Iguana

Ecological data, the primary source of information on patterns and rates of migration, can be integrated with genetic data to more accurately describe the realized connectivity between geographically isolated demes. In this paper we implement this approach and discuss its implications for managing populations of the endangered Andros Island Rock Iguana, Cyclura cychlura cychlura. This iguana is endemic to Andros, a highly fragmented landmass of large islands and smaller cays. Field observations suggest that geographically isolated demes were panmictic due to high, inferred rates of gene flow. We expand on these observations using 16 polymorphic microsatellites to investigate the genetic structure and rates of gene flow from 188 Andros Iguanas collected across 23 island sites. Bayesian clustering of specimens assigned individuals to three distinct genotypic clusters. An analysis of molecular variance (AMOVA) indicates that allele frequency differences are responsible for a significant portion of the genetic variance across the three defined clusters (F_st =  0.117, p0.01). These clusters are associated with larger islands and satellite cays isolated by broad water channels with strong currents. These findings imply that broad water channels present greater obstacles to gene flow than was inferred from field observation alone. Additionally, rates of gene flow were indirectly estimated using BAYESASS 3.0. The proportion of individuals originating from within each identified cluster varied from 94.5 to 98.7%, providing further support for local isolation. Our assessment reveals a major disparity between inferred and realized gene flow. We discuss our results in a conservation perspective for species inhabiting highly fragmented landscapes.     

Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population

Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The −13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (LCT) in the MCM6 gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The −13779*C,−13910*T, −13937*A, −14010*C, −14011*T LP alleles previously described in the MCM6 gene region that acts as an enhancer for the LCT gene were identified in Brazilians. The most common LP allele was −13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The −13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. LCT haplotypes were derived from the 10 LCT SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of LCT haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the −13910*T allele is an oversimplification.