Genome-wide Sequence Data Research Articles

Rapid diversification of the Variable Seedeater superspecies complex despite widespread gene flow

Disentangling the evolutionary relationships of rapidly radiating clades is often challenging because of low genetic differentiation and potentially high levels of gene flow among diverging taxa. The genus Sporophila consists of small Neotropical birds that show, in general, relatively low genetic divergence, but particularly high speciation rates and pronounced variation in secondary sexual traits (e.g., plumage color), which can be important in generating premating reproductive isolation. In cases like these, the use of genome-wide sequence data can increase the resolution to uncover a clade’s evolutionary history. Here, we used a phylogenomic approach to study the evolutionary history and genetic structure of the Variable Seedeater superspecies complex, which includes S. corvina, S. intermedia, and S. americana. Using ∼25,000 genome-wide single nucleotide polymorphisms (SNPs), we confirmed that the Variable Seedeater superspecies complex is monophyletic. However, a phylogenetic reconstruction based on a mitochondrial marker (ND2) resulted in a discordant tree topology, particularly in the position of Wing-barred Seedeater S. americana, which might be due to a mitochondrial capture event. Our results suggest historical gene flow among lineages, particularly between species with conflicting topologies. Among the four phenotypically variable S. corvina subspecies, our structure analyses identified three main distinct genetic groups (K = 3), and that the entirely black subspecies, S. c. corvina, is derived from within a pied-colored clade. Further, we inferred widespread gene flow across the whole species’ distribution, including between subspecies. However, gene flow was about 100 times lower at the geographic boundaries of the entirely black and the pied subspecies, suggesting an important role for plumage divergence in limiting gene flow. Overall, our findings suggest that the early diversification of the Sporophila genus occurred rapidly despite historical gene flow between lineages and that divergence in plumage color possibly influences the extent of gene flow among taxa.

Loss-of-function of KMT5B leads to neurodevelopmental disorder and impairs neuronal development and neurogenesis

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that cause severe social, communication, and behavioral problems. Recent studies show that the variants of a histone methyltransferase gene KMT5B cause neurodevelopmental disorders (NDDs), including ASD, and the knockout of Kmt5b in mice is embryonic lethal. However, the detailed genotype-phenotype correlations and functional effects of KMT5B in neurodevelopment are unclear. By targeted sequencing of a large Chinese ASD cohort, analyzing published genome-wide sequencing data, and mining literature, we curated 39 KMT5B variants identified from NDD individuals. A genotype-phenotype correlation analysis for 10 individuals with KMT5B pathogenic variants reveals common symptoms, including ASD, intellectual disability, languages problem, and macrocephaly. In vitro knockdown of the expression of Kmt5b in cultured mouse primary cortical neurons leads to a decrease in neuronal dendritic complexity and an increase in dendritic spine density, which can be rescued by expression of human KMT5B but not that of pathogenic de novo missense mutants. In vivo knockdown of the Kmt5b expression in the mouse embryonic cerebral cortex by in utero electroporation results in decreased proliferation and accelerated migration of neural progenitor cells. Our findings reveal essential roles of histone methyltransferase KMT5B in neuronal development, prenatal neurogenesis, and neuronal migration.

Adipose Triglyceride Lipase Deficiency Attenuates In Vitro Thrombus Formation without Affecting Platelet Activation and Bleeding In Vivo.

According to genome-wide RNA sequencing data from human and mouse platelets, adipose triglyceride lipase (ATGL), the main lipase catalyzing triglyceride (TG) hydrolysis in cytosolic lipid droplets (LD) at neutral pH, is expressed in platelets. Currently, it is elusive to whether common lipolytic enzymes are involved in the degradation of TG in platelets. Since the consequences of ATGL deficiency in platelets are unknown, we used whole-body and platelet-specific (plat)Atgl-deficient (−/−) mice to investigate the loss of ATGL on platelet function. Our results showed that platelets accumulate only a few LD due to lack of ATGL. Stimulation with platelet-activating agonists resulted in comparable platelet activation in Atgl−/−, platAtgl−/−, and wild-type mice. Measurement of mitochondrial respiration revealed a decreased oxygen consumption rate in platelets from Atgl−/− but not from platAtgl−/− mice. Of note, global loss of ATGL was associated with an anti-thrombogenic phenotype, which was evident by reduced thrombus formation in collagen-coated channels in vitro despite unchanged bleeding and occlusion times in vivo. We conclude that genetic deletion of ATGL affects collagen-induced thrombosis without pathological bleeding and platelet activation.

Generic boundaries in the Ophiostomatales reconsidered and revised.

The Ophiostomatales was erected in 1980. Since that time, several of the genera have been redefined and others have been described. There are currently 14 accepted genera in the Order. They include species that are the causal agents of plant and human diseases and common associates of insects such as bark beetles. Well known examples include the Dutch elm disease fungi and the causal agents of sporotrichosis in humans and animals. The taxonomy of the Ophiostomatales was confused for many years, mainly due to the convergent evolution of morphological characters used to delimit unrelated fungal taxa. The emergence of DNA-based methods has resolved much of this confusion. However, the delineation of some genera and the placement of various species and smaller lineages remains inconclusive. In this study we reconsidered the generic boundaries within the Ophiostomatales. A phylogenomic framework constructed from genome-wide sequence data for 31 species representing the major genera in the Order was used as a guide to delineate genera. This framework also informed our choice of the best markers from the currently most commonly used gene regions for taxonomic studies of these fungi. DNA was amplified and sequenced for more than 200 species, representing all lineages in the Order. We constructed phylogenetic trees based on the different gene regions and assembled a concatenated data set utilising a suite of phylogenetic analyses. The results supported and confirmed the delineation of nine of the 14 currently accepted genera, i.e.Aureovirgo, Ceratocystiopsis, Esteya, Fragosphaeria, Graphilbum, Hawksworthiomyces, Ophiostoma, Raffaelea and Sporothrix. The two most recently described genera, Chrysosphaeria and Intubia, were not included in the multi-locus analyses. This was due to their high sequence divergence, which was shown to result in ambiguous taxonomic placement, even though the results of phylogenomic analysis supported their inclusion in the Ophiostomatales. In addition to the currently accepted genera in the Ophiostomatales, well-supported lineages emerged that were distinct from those genera. These are described as novel genera. Two lineages included the type species ofGrosmannia andDryadomyces and these genera are thus reinstated and their circumscriptions redefined. The descriptions of all genera in the Ophiostomatales were standardised and refined where this was required and 39 new combinations have been provided for species in the newly emerging genera and one new combination has been provided for Sporothrix. The placement of Afroraffaelea could not be confirmed using the available data and the genus has been treated as incertae sedis in the Ophiostomatales. Paleoambrosia was not included in this study, due to the absence of living material available for this monotypic fossil genus. Overall, this study has provided the most comprehensive and robust phylogenies currently possible for the Ophiostomatales. It has also clarified several unresolved One Fungus-One Name nomenclatural issues relevant to the Order.

Estimating dispersal using close kin dyads: The kindisperse R package

Investigating dispersal in animal populations can be difficult, particularly for taxa that are hard to directly observe such as those that are small or rare. A promising solution may come from new approaches that use genome-wide sequence data to detect close kin dyads and estimate dispersal parameters from the distribution of these dyads. These methods have so far only been applied to mosquito populations. However, they should have broad applicability to a range of taxa, although no assessment has yet been made on their performance under different dispersal conditions and study designs. Here we develop an R package and shiny app, kindisperse, that can be used to estimate dispersal parameters from the spatial distribution of close kin. kindisperse can handle study designs that target different life stages and allows for a range of dispersal kernel shapes and organismal life histories; we provide implementation examples for a vertebrate (Antechinus) and an invertebrate (Aedes). We use simulations run in kindisperse to compare the performance of two published close kin methodologies, showing that one method produces unbiased estimates whereas the other produces downward-biased estimates. We also use kindisperse simulations to investigate how study design affects dispersal estimates, and we provide guidelines for the size and shape of sample sites as well as the number of close kin needed for accurate estimates. kindisperse is easily adaptable for application to a variety of research contexts ranging from invasive pests to threatened species where noninvasive DNA sampling can be used to detect close kin.

Phylogenomic Species Delimitation Dramatically Reduces Species Diversity in an Antarctic Adaptive Radiation.

Application of genetic data to species delimitation often builds confidence in delimitations previously hypothesized using morphological, ecological, and geographic data and frequently yields recognition of previously undescribed cryptic diversity. However, a recent critique of genomic data-based species delimitation approaches is that they have the potential to conflate population structure with species diversity, resulting in taxonomic oversplitting. The need for an integrative approach to species delimitation, in which molecular, morphological, ecological, and geographic lines of evidence are evaluated together, is becoming increasingly apparent. Here, we integrate phylogenetic, population genetic, and coalescent analyses of genome-wide sequence data with investigation of variation in multiple morphological traits to delimit species within the Antarctic barbeled plunderfishes (Artedidraconidae: Pogonophryne). Pogonophryne currently comprises 29 valid species, most of which are distinguished solely by variation in the ornamentation of the mental barbel that projects from the lower jaw, a structure previously shown to vary widely within a single species. However, our genomic and phenotypic analyses result in a dramatic reduction in the number of distinct species recognized within the clade, providing evidence to support the recognition of no more than six species. We propose to synonymize 24 of the currently recognized species with five species of Pogonophryne. We find genomic and phenotypic evidence for a new species of Pogonophryne from specimens collected in the Ross Sea. Our findings represent a rare example in which the application of molecular data provides evidence of taxonomic oversplitting on the basis of morphology, clearly demonstrating the utility of an integrative species delimitation framework.[ddRADseq; multispecies coalescent; Notothenioidei; SNPs; Southern Ocean.].

Genomic Landscapes of Noncoding RNAs Regulating VEGFA and VEGFC Expression in Endothelial Cells.

ABSTRACTVascular endothelial growth factors (VEGFs) are best known as key regulators of angiogenesis and lymphangiogenesis. Although VEGFs have been promising therapeutic targets for various cardiovascular diseases, their regulatory landscape in endothelial cells remains elusive. Several studies have highlighted the involvement of noncoding RNAs (ncRNAs) in the modulation of VEGF expression. In this study, we investigated the role of two classes of ncRNAs, long ncRNAs (lncRNAs) and enhancer RNAs (eRNAs), in the transcriptional regulation of VEGFA and VEGFC. By integrating genome-wide global run-on sequencing (GRO-Seq) and chromosome conformation capture (Hi-C) data, we identified putative lncRNAs and eRNAs associated with VEGFA and VEGFC genes in endothelial cells. A subset of the identified putative enhancers demonstrated regulatory activity in a reporter assay. Importantly, we demonstrate that deletion of enhancers and lncRNAs by CRISPR/Cas9 promoted significant changes in VEGFA and VEGFC expression. Transcriptome sequencing (RNA-Seq) data from lncRNA deletions showed downstream factors implicated in VEGFA- and VEGFC-linked pathways, such as angiogenesis and lymphangiogenesis, suggesting functional roles for these lncRNAs. Our study uncovers novel lncRNAs and eRNAs regulating VEGFA and VEGFC that can be targeted to modulate the expression of these important molecules in endothelial cells.

Biological properties and genetic characteristics of experimental diagnostic Vibrio cholerae bacteriophages

Background. Currently, the researches focused on the design of new diagnostic and preventive preparations based on bacteriophages are underway, so it is importatnt to study the biological properties of cholera phages along with their genetic structure. This information is necessary to predict the phage life cycle and assess the prospects of its practical use in experiments, phagodiagnostics and phagoprophylaxis.Materials and methods. The presence or absence of genes characteristic of temperate bacteriophages was tested using a database created by the authors and developed software "PhageAnalyzer", which allows for rapid analysis of bacteriophage genome-wide sequencing data and prediction of their life cycle.Results and discussion. The morphological structure of experimental diagnostic cholera phages is represented by head bacteriophages of various morphogroups. Negative colonies phage differed in diameter, shape and degree of transparency. No genetic determinants of resistance factors and toxins have been found in the genomes of bacteriophages Rostov-1, Rostov-6, Rostov 7, and Rostov M3. Results of phylogenetic analysis demonstrated that the studied experimental cholera bacteriophages resemble headphages from the genus Vibrio, but are unique, since they lie outside “cluster groups”. Vibrio phages Rostov-1 and Rostov M3 are appeared to be lytic. Genes characteristic of moderate bacteriophages were found in cholera phages Rostov-6 and Rostov 7.Conclusion. The experimental cholera bacteriophage Rostov-1 can be used to differentiate cholera vibrion O1 the serogroup of the El Tor biovar, and Vibrio phage Rostov M3 can be used to differentiate the Classical biovar. Both bacteriophages are lytic and promising components for creating prophylactic drugs against cholera. Vibrio phages Rostov-6 and Rostov 7 can be successfully used only in experimental activities, as well as for monitoring cholera vibrions in the environment. Complete genomic sequences are deposited and available in the international database Genbank (NCBI).

Integrated Molecular Profiling of Juvenile Myelomonocytic Leukemia

Introduction: Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm that occurs in infancy and early childhood, characterized by excessive myelomonocytic cell proliferation and granulocyte-macrophage colony-stimulating factor hypersensitivity. Over 80% of JMML patients have been reported to harbor mutually exclusive somatic and/or germline mutations in canonical RAS pathway genes (e.g., PTPN11, NF1, NRAS, KRAS, and CBL), and previous studies have identified several poor prognostic factors, including the presence of two or more mutations, acute myeloid leukemia-like (AML-like) gene expression profiles, and selected gene promoter methylation profiles. However, the molecular pathogenesis in 10%-20% of patients and the relationships among biomarkers have not been well defined. This study aimed to assess the molecular pathogenesis in patients and the relationships among several biomarkers and outcomes.Patients and Methods: We performed comprehensive genetic analyses in 150 JMML patients, including 15 with Noonan syndrome-associated myeloproliferative disorder (NS/MPD), using whole-exome sequencing (n = 69, 46%), targeted deep sequencing (n = 92, 61%), RNA sequencing (n = 129, 86%), and genome-wide methylation analysis (n = 106, 71%).Results: We identified ALK/ROS1 tyrosine kinase fusions (DCTN1-ALK, RANBP2-ALK, and TBL1XR1-ROS1) in three of 16 patients (18%) who lacked canonical RAS pathway mutations. Crizotinib, an ALK/ROS1 inhibitor, markedly suppressed ALK/ROS1 fusion-positive JMML cell proliferation in vitro . Therefore, we administered crizotinib to a patient with the RANBP2-ALK fusion gene. This patient achieved complete molecular remission after the administration of crizotinib for 51 days and successfully bridged to allogeneic stem cell transplantation. This patient survived without disease recurrence for 15 months after transplantation.We performed a genome-wide methylation analysis in 106 patients and combined the data with repository data from normal CD34+ samples (n = 5) and AML CD34+CD38− samples (n = 14) for an unsupervised consensus clustering of CpG methylation profiles, which yielded two distinct subgroups, hypermethylation profile (n = 45, 42%) and hypomethylation profile (n = 61, 58%). All AML samples had a hypermethylation profile, whereas all normal CD34+ and NS/MPD samples had a hypomethylation profile. A gene set enrichment analysis revealed marked enrichment of AML-associated genes in the hypermethylation cluster. The 5-year OS rate was 46.0% [95% confidence interval (CI), 31.0%-59.8%] among patients with a hypermethylation profile and 73.4% (95% CI, 57.6%-84.1%) among those with a hypomethylation profile (p = 0.0028). The 5-year TFS was significantly poorer in the hypermethylation group than in the hypomethylation group [2.2% (95% CI, 0.2%-10.1%) vs. 41.2% (95% CI, 27.1%-54.8%), p = 3.1 × 10−10]. Differential gene expression analysis for the hypermethylation and hypomethylation profiles revealed overexpression of LIN28B and its downstream target HMGA2 in the hypermethylation profile.Lastly, we integrated the molecular analyses of JMML, including genome-wide methylation profiling, RNA sequencing, and resequencing data and found that the hypermethylation profile was highly correlated with the most established risk factors for JMML, including older age, higher HbF level, lower platelet count, PTPN11/NF1 mutations, presence of two or more mutations, LIN28B overexpression, and AML-like expression profiles, as well as poor survival.Discussion: We identified recurrent activated ALK/ROS1 fusions in JMML patients without canonical RAS pathway gene mutations. Crizotinib represents a promising candidate drug for treating JMML in patients with ALK/ROS1 fusions. In addition, we established a risk profiling system based on genome-wide methylation analysis and showed that the hypermethylation profile is highly associated with poor survival and most established poor prognostic biomarkers for JMML. These finding will contribute to the development of precision treatments for JMML patients. DisclosuresNo relevant conflicts of interest to declare.

A method for the temperature-controlled extraction of DNA from ancient bones.

Contamination with microbial and other exogenous DNA poses a significantchallenge in the generation of genome-wide sequence data from ancient skeletal remains. Here we describe a method for separating ancient DNA into multiple fractions during DNA extraction by sequential temperature-controlled release of DNA into sodium phosphate buffer. An evaluation of the effectiveness of the method using a set of three ancient bones resulted in between 1.6- and 32-fold enrichment of endogenous DNA compared with regular DNA extraction. For two bones, the method outperformed previous methods of decontaminating ancient bones, including hypochlorite treatment, which resulted in near-complete destruction of DNA in the worst-preserved sample. This extractionmethod expands the spectrum of methods available for depleting contaminant DNA from ancient skeletal remains.

An Integrative Transcriptomic and Methylation Approach for Identifying Differentially Expressed Circular RNAs Associated with DNA Methylation Change.

Recently, accumulating evidence has supported that circular RNA (circRNA) plays important roles in tumorigenesis by regulating gene expression at transcriptional and post-transcriptional levels. Expression of circRNAs can be epigenetically silenced by DNA methylation; however, the underlying regulatory mechanisms of circRNAs by DNA methylation remains largely unknown. We explored this regulation in hepatocellular carcinoma (HCC) using genome-wide DNA methylation and RNA sequencing data of the primary tumor and matched adjacent normal tissues from 20 HCC patients. Our pipeline identified 1012 upregulated and 747 downregulated circRNAs (collectively referred to as differentially expressed circRNAs, or DE circRNAs) from HCC RNA-seq data. Among them, 329 DE circRNAs covered differentially methylated sites (adjusted p-value < 0.05, |ΔM| > 0.5) in circRNAs’ interior and/or flanking regions. Interestingly, the corresponding parental genes of 46 upregulated and 31 downregulated circRNAs did not show significant expression change in the HCC tumor versus normal samples. Importantly, 34 of the 77 DE circRNAs (44.2%) had significant correlation with DNA methylation change in HCC (Spearman’s rank-order correlation, p-value < 0.05), suggesting that aberrant DNA methylation might regulate circular RNA expression in HCC. Our study revealed genome-wide differential circRNA expression in HCC. The significant correlation with DNA methylation change suggested that epigenetic regulation might act on both mRNA and circRNA expression. The specific regulation in HCC and general view in other cancer or disease requires further investigation.

Computational systems-biology approaches for modeling gene networks driving epithelial-mesenchymal transitions.

Epithelial–mesenchymal transition (EMT) is an important biological process through which epithelial cells undergo phenotypic transitions to mesenchymal cells by losing cell–cell adhesion and gaining migratory properties that cells use in embryogenesis, wound healing, and cancer metastasis. An important research topic is to identify the underlying gene regulatory networks (GRNs) governing the decision making of EMT and develop predictive models based on the GRNs. The advent of recent genomic technology, such as single-cell RNA sequencing, has opened new opportunities to improve our understanding about the dynamical controls of EMT. In this article, we review three major types of computational and mathematical approaches and methods for inferring and modeling GRNs driving EMT. We emphasize (1) the bottom-up approaches, where GRNs are constructed through literature search; (2) the top-down approaches, where GRNs are derived from genome-wide sequencing data; (3) the combined top-down and bottom-up approaches, where EMT GRNs are constructed and simulated by integrating bioinformatics and mathematical modeling. We discuss the methodologies and applications of each approach and the available resources for these studies.

Automated improvement of stickleback reference genome assemblies with Lep-Anchor software.

We describe an integrative approach to improve contiguity and haploidy of a reference genome assembly and demonstrate its impact with practical examples. With two novel features of Lep-Anchor software and a combination of dense linkage maps, overlap detection and bridging long reads, we generated an improved assembly of the nine-spined stickleback (Pungitius pungitius) reference genome. We were able to remove a significant number of haplotypic contigs, detect more genetic variation and improve the contiguity of the genome, especially that of X chromosome. However, improved scaffolding cannot correct for mosaicism of erroneously assembled contigs, demonstrated by a de novo assembly of a 1.6-Mbp inversion. Qualitatively similar gains were obtained with the genome of three-spined stickleback (Gasterosteus aculeatus). Since the utility of genome-wide sequencing data in biological research depends heavily on the quality of the reference genome, the improved and fully automated approach described here should be helpful in refining reference genome assemblies.

Most Genomic Loci Misrepresent the Phylogeny of an Avian Radiation Because of Ancient Gene Flow.

Phylogenetic trees based on genome-wide sequence data may not always represent the true evolutionary history for a variety of reasons. One process that can lead to incorrect reconstruction of species phylogenies is gene flow, especially if interspecific gene flow has affected large parts of the genome. We investigated phylogenetic relationships within a clade comprising eight species of passerine birds (Phylloscopidae, Phylloscopus, leaf warblers) using one de novo genome assembly and 78 resequenced genomes. On the basis of hypothesis-exclusion trials based on D-statistics, phylogenetic network analysis, and demographic inference analysis, we identified ancient gene flow affecting large parts of the genome between one species and the ancestral lineage of a sister species pair. This ancient gene flow consistently caused erroneous reconstruction of the phylogeny when using large amounts of genome-wide sequence data. In contrast, the true relationships were captured when smaller parts of the genome were analyzed, showing that the “winner-takes-all democratic majority tree” is not necessarily the true species tree. Under this condition, smaller amounts of data may sometimes avoid the effects of gene flow due to stochastic sampling, as hidden reticulation histories are more likely to emerge from the use of larger data sets, especially whole-genome data sets. In addition, we also found that genomic regions affected by ancient gene flow generally exhibited higher genomic differentiation but a lower recombination rate and nucleotide diversity. Our study highlights the importance of considering reticulation in phylogenetic reconstructions in the genomic era.[Bifurcation; introgression; recombination; reticulation; Phylloscopus.]

Resolving phylogeny and polyploid parentage using genus-wide genome-wide sequence data from birch trees

Numerous plant genera have a history including frequent hybridisation and polyploidisation (allopolyploidisation), which means that their phylogeny is a network of reticulate evolution that cannot be accurately depicted as a bifurcating tree with a single tip per species. The genus Betula, which contains many ecologically important tree species, is a case in point. We generated genome-wide sequence reads for 27 diploid and 36 polyploid Betula species or subspecies using restriction site associated DNA (RAD) sequences. These reads were assembled into contigs with a mean length of 675 bp. We reconstructed the evolutionary relationships among diploid Betula species using both supermatrix (concatenation) and species tree methods. We identified the closest diploid relatives of the polyploids according to the relative rates at which reads from polyploids mapped to contigs from different diploid species within a concatenated reference sequence. By mapping reads from allopolyploids to their different putative diploid relatives we assembled contigs from the putative sub-genomes of allopolyploid taxa. We used these to build new phylogenies that included allopolyploid sub-genomes as separate tips. This approach yielded a highly evidenced phylogenetic hypothesis for the genus Betula, including the complex reticulate origins of the majority of its polyploid taxa. Our phylogeny divides the genus into two well supported clades, which, interestingly, differ in their seed-wing morphology. We therefore propose to split Betula into two subgenera.

Genome-wide supermatrix analyses of maples (Acer, Sapindaceae) reveal recurring inter-continental migration, mass extinction, and rapid lineage divergence

Acer (Sapindaceae) is an exceptional study system for understanding the evolutionary history, divergence, and assembly of broad-leaved deciduous forests at higher latitudes. Maples stand out due to their high diversity, disjunct distribution pattern across the northern continents, and rich fossil record dating back to the Paleocene. Using a genome-wide supermatrix combining plastomes and nuclear sequences (~585 kb) for 110 Acer taxa, we built a robust time-calibrated hypothesis investigating the evolution of maples, inferring ancestral ranges, reconstructing diversification rates over time, and exploring the impact of mass-extinction on lineage accumulation. Contrary to fossil evidence, our results indicate Acer first originated in the (north)eastern Palearctic region, which acted as a source for recurring outward migration. Warm conditions favored rapid Eocene-onward divergence, but ranges and diversity declined extensively as a result of the Plio-Pleistocene glacial cycles. These signals in genome-wide sequence data corroborate paleobotanical evidence for other major woody north-temperate groups, highlighting the significant (disparate) impact of climatic changes on the evolution, composition, and distribution of the vegetation in the northern hemisphere.

Genetic ancestry changes in Stone to Bronze Age transition in the East European plain.

The transition from Stone to Bronze Age in Central and Western Europe was a period of major population movements originating from the Ponto-Caspian Steppe. Here, we report new genome-wide sequence data from 30 individuals north of this area, from the understudied western part of present-day Russia, including 3 Stone Age hunter-gatherers (10,800 to 4250 cal BCE) and 26 Bronze Age farmers from the Corded Ware complex Fatyanovo Culture (2900 to 2050 cal BCE). We show that Eastern hunter-gatherer ancestry was present in northwestern Russia already from around 10,000 BCE. Furthermore, we see a change in ancestry with the arrival of farming-Fatyanovo Culture individuals were genetically similar to other Corded Ware cultures, carrying a mixture of Steppe and European early farmer ancestry. Thus, they likely originate from a fast migration toward the northeast from somewhere near modern-day Ukraine-the closest area where these ancestries coexisted from around 3000 BCE.

The use of genomic data and imputation methods in dairy cattle breeding

The inclusion of animal genotype data has contributed to the development of genomic selection. Animals are selected not only based on pedigree and phenotypic data but also on the basis of information about their genotypes. Genomic information helps to increase the accuracy of selection of young animals and thus enables a reduction of the generation interval. Obtaining information about genotypes in the form of SNPs (single nucleotide polymorphisms) has led to the development of new chips for genotyping. Several methods of genomic comparison have been developed as a result. One of the methods is data imputation, which allows the missing SNPs to be calculated using low-density chips to high-density chips. Through imputations, it is possible to combine information from diverse sets of chips and thus obtain more information about genotypes at a lower cost. Increasing the amount of data helps increase the reliability of predicting genomic breeding values. Imputation methods are increasingly used in genome-wide association studies. When classical genotyping and genome-wide sequencing data are combined, this option helps to increase the chances of identifying loci that are associated with economically significant traits.

Individualistic evolutionary responses of Central African rain forest plants to Pleistocene climatic fluctuations

Understanding the evolutionary dynamics of genetic diversity is fundamental for species conservation in the face of climate change, particularly in hyper-diverse biomes. Species in a region may respond similarly to climate change, leading to comparable evolutionary dynamics, or individualistically, resulting in dissimilar patterns. The second-largest expanse of continuous tropical rain forest (TRF) in the world is found in Central Africa. Here, present-day patterns of genetic structure are thought to be dictated by repeated expansion and contraction of TRFs into and out of refugia during Pleistocene climatic fluctuations. This refugia model implies a common response to past climate change. However, given the unrivalled diversity of TRFs, species could respond differently because of distinct environmental requirements or ecological characteristics. To test this, we generated genome-wide sequence data for >700 individuals of seven codistributed plants from Lower Guinea in Central Africa. We inferred species' evolutionary and demographic histories within a comparative phylogeographic framework. Levels of genetic structure varied among species and emerged primarily during the Pleistocene, but divergence events were rarely concordant. Demographic trends ranged from repeated contraction and expansion to continuous growth. Furthermore, patterns in genetic variation were linked to disparate environmental factors, including climate, soil, and habitat stability. Using a strict refugia model to explain past TRF dynamics is too simplistic. Instead, individualistic evolutionary responses to Pleistocene climatic fluctuations have shaped patterns in genetic diversity. Predicting the future dynamics of TRFs under climate change will be challenging, and more emphasis is needed on species ecology to better conserve TRFs worldwide.

Population genetic analysis of the Plasmodium falciparum circumsporozoite protein in two distinct ecological regions in Ghana

BackgroundExtensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. The transmission intensity and rates of recombination within and between populations influence the extent of its genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria-endemic areas such as Ghana.MethodsPfcsp sequences were retrieved from the Illumina-generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6–59 months presenting with clinical malaria at health facilities in Cape Coast (in the coastal belt) and Navrongo (Guinea savannah region), respectively, in Ghana. The sequences were mapped onto the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analysed for the allele frequency spectrum, genetic diversity both within the host and between populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana.ResultsPfcsp showed extensive diversity at the two sites, with the higher transmission site, Navrongo, exhibiting higher within-host and population-level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences, respectively. Between 1 and 6 amino acid variations were observed in the TH2R and TH3R epitope regions of PfCSP. Tajima’s D was negatively skewed, especially for the population from Cape Coast, given the expected historical population expansion. In contrast, a positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes.ConclusionThe low frequencies of the Pfcsp vaccine haplotype in the analysed populations indicate a need for additional molecular and immuno-epidemiological studies with broader temporal and geographic sampling in endemic populations targeted for RTS,S application. These results have implications for the efficacy of the vaccine in Ghana and will inform the choice of alleles to be included in future multivalent or chimeric vaccines.