Genetics

Many functionally connected loci foster adaptive diversification along a neotropical hybrid zone – Science Advances

Abstract

Characterizing the genetic complexity of adaptation and trait evolution is a major emphasis of evolutionary biology and genetics. Incongruent findings from genetic studies have resulted in conceptual models ranging from a few large-effect loci to massively polygenic architectures. Here, we combine chromatin immunoprecipitation sequencing, Hi-C, RNA sequencing, and 40 whole-genome sequences from Heliconius butterflies to show that red color pattern diversification occurred via many genomic loci. We find that the red wing pattern master regulatory transcription factor Optix binds dozens of loci also under selection, which frequently form three-dimensional adaptive hubs with selection acting on multiple physically interacting genes. Many Optix-bound genes under selection are tied to pigmentation and wing development, and these loci collectively maintain separation between adaptive red color pattern phenotypes in natural populations. We propose a model of trait evolution where functional connections between loci may resolve much of the disparity between large-effect and polygenic evolutionary models.

Identifying the genetic basis of both the origin and maintenance of adaptive traits is essential for the study of diversification. Recent studies disagree, however, on the complexity of adaptive trait architecture, largely because approaches used for genetic mapping are often inconsistent. Quantitative trait loci (QTL) studies investigating the genetic basis of adaptive traits have repeatedly mapped natural variation to a few Mendelian loci (1, 2). Similarly, studies of the loci differentiating adaptive phenotypes in hybrid zones frequently find a handful of genes that strongly segregate by phenotype (35). Yet, these observations are increasingly incongruent with genome-wide association studies (GWAS), selection associated with trait variation, and studies incorporating artificial selection, which all regularly find many natural genetic variants of differing effect sizes that associate with trait variation (68). This has led to several proposals that many traits may be highly or massively polygenic (9, 10). An oligogenic or polygenic architecture would, in turn, suggest that a larger subset of causal variants might also contribute to maintaining adaptive traits between hybridizing taxa. The discrepancy between QTL studies, known for bias toward a few loci of large effect, and the often multigenic composition of natural trait-associated variation is not new, yet reconciliation of these disparate findings has been a challenge (9).

Here, we study hybridizing populations of Heliconius erato butterflies as a natural model for resolving this conflict. In Ecuador and Peru, evolutionarily derived Radiate morphs of H. erato form hybrid zones along the Andes with several Postman morphs (Fig. 1A) (5). In this region, genome-wide divergence is low, effective population sizes are high (11), gene flow is frequent between hybridizing morphs (12), and populations are only strongly differentiated by three known color patternassociated loci around WntA, cortex, and optix (Fig. 1B). The master regulator gene optix acts as a classic Mendelian gene of large effect, and both QTL studies and scans for genomic differentiation in hybrid zones have mapped control of adaptive red mimicry color pattern variation to optix (3, 1316). Recent study of the Radiate phenotype in H. erato found that wing patterns evolved via selection on at least five pleiotropic cis-regulatory loci and that these elements were shared by all Radiate morphs through adaptive introgression (17). Yet, despite the singular importance of optix for red wing pattern evolution, studies in Heliconius have found that quantitative variation in red wing patterns maps to at least 15 of the 21 chromosomes in Heliconius (shown in Fig. 1C), indicating that many more loci may be important contributors to red color pattern adaptation in the genus (1821). In this study, we investigate the population genetic signatures of additional loci associated with adaptive diversification and assess the extent to which these may be functionally connected to optix.

(A) Postman (western) and Radiate (eastern) metapopulations show Andean hybrid zone between morphs. (B) Genomic differentiation between Radiate and Postman metapopulations with three major color pattern loci annotated. (C) Signatures of selective sweeps in the Radiate metapopulation shows many loci under selection. Bars mark chromosomes significantly associated with red pattern variation in H. melpomene (red) and H. erato (orange).

We predicted that additional loci in the optix gene network may have contributed to the adaptive diversification of the Radiate morphology. Because Optix is a transcription factor that binds cis-regulatory elements (CREs; fig. S1A), focusing on Optix-bound loci limited our analysis to genes directly regulated by the master regulator of red wing coloration in butterflies. To test for additional adaptive evolution causally linked to red color pattern variation in H. erato, we intersected a whole genome scan for selective sweeps using SweepFinder2 (22) in a metapopulation of Radiate morphs (Fig. 1C) with downstream targets of the Optix protein in midpupal wing tissue. Consistent with the hypothesis that much of the Optix-associated gene network may be under selection, Optix-bound CREs showed significantly greater evidence of selective sweeps than expected from CREs drawn randomly from wing assay for transposase-accessible chromatin sequencing (ATAC-seq) data at the same developmental stage (Fig. 2A). The composite likelihood ratio produced by SweepFinder2 is capable of detecting hard sweeps (22), introgressed sweeps (23), and, to a lesser extent, soft sweeps [e.g., (24)]. Thus, much of the enriched composite likelihood ratio (CLR) signal observed at Optix-bound CREs is likely due to selection on alleles with varying origins and evolutionary histories, and some additional soft sweeps may be identified in future studies.

(A) Optix binding sites show significantly greater signatures of selective sweeps than expected from annotated CREs chosen randomly from the same developmental stage. The 99.5th percentile line shows the cutoff threshold for strong signals of selection, and bracket highlights the number of Optix-bound and control loci above this threshold. (B) Optix-bound loci with strong signals of selection often form three-dimensional (3D) adaptive hubs. (C) Adaptive hub transcriptional start sites (TSSs) show elevated selection compared to other regulatory elements. (D) Functional characterization of known genes at loci with strong signals of selection and adaptive hubs are often pigment associated.

We next used physical, Hi-Cbased evidence of CRE-to-gene interactions to link Optix binding sites to gene promoters and selected CREs intersecting with selective sweep values (CLR) in the top 0.5% of all CLR scores as loci displaying strong signals of positive selection (fig. S1, B and C). Fifty-nine loci met the criteria of Optix binding and high CLR values and were designated as additional loci of putative adaptive evolution driven by changing optix expression domains (Fig. 2B). Targets of the Optix protein displaying a strong signal of selection were found on 15 of 21 chromosomes, including all but two chromosomes implicated in red color pattern variation (Fig. 1C and fig. S2A) (1821). Together, evidence of increased selection on Optix binding sites and numerous loci with strong signals of selection in the Radiate metapopulation provide compelling support for a multigenic adaptive process such as the two-step model proposed by Sheppard et al. (13) and Baxter et al. (20).

Our finding that Optix binding sites are generally under increased selection pressure led us to investigate the three-dimensional landscape of adaptation at loci with strong signatures of selection. To accomplish this, we compared our results to RNA sequencing (RNA-seq) assays of differential gene expression between wing tissue of Radiate and Postman butterflies at the same developmental stage (25). We found that 65% of Optix binding sites that display strong signals of selection formed cis-acting adaptive hubs, characterized by a single CRE in the top 0.5% of CLR values that physically connects with two or more genes that are differentially expressed between Radiate and Postman butterflies (Fig. 2C). Adaptive hubs are defined locally by the presence of an Optix binding site with a strong signal of selection in the Radiate metapopulation, with Hi-C evidence of physical loops to at least two additional transcriptional start sites (TSS) of genes differentially expressed between wing pattern morphs. Thus, adaptive hubs are cis-acting networks of genes in close physical proximity that are regulated by Optix and associated with color pattern variation between morphs. This differs from developmental hubs derived from statistical analysis of network connectivity that focus primarily on identifying large-scale genetic interaction networks with both cis and trans interactions [e.g., (26, 27)]. Adaptive hub genes, excluding the hub center with a strong signal of selection, displayed significantly greater signatures of selection than expected when compared to both all genomic loci tested (all CLR values) and selection at all annotated gene TSSs (Fig. 2D). The median CLR value of hub genes indicated a moderate degree of selection and was greater than the 95th percentile of either control dataset. Consistent with our previous results showing increased selection on Optix-bound loci, two-thirds of adaptive hub genes were also bound by Optix, suggesting that selection can favor specific three-dimensional Optix-associated landscapes in addition to individual gene alleles.

We next annotated the function of known genes at adaptive hubs and loci with strong signatures of selection to determine the composition of putative adaptive loci. In total, 160 genes with known functions were linked to strong signals of selection on the Radiate optix expression domain, as determined by selection on Optix-bound TSSs or selection on distal CREs looping to the relevant TSS. Of these, 25% (39) had annotated pigmentation or wing patternassociated gene functions, including some well-characterized pigmentation genes, while an additional 8% (13) of genes performed a role in important signaling pathways such as the Toll or Dpp pathways (Fig. 2D and fig. S2B). Incorporation of pigmentation, patterning, and signaling genes with genes of other, less obvious functions points to a complex adaptive process targeting wing colorpatterning genes, biochemical processes, and potentially even compensatory mutations to account for maladaptive effects of the changing optix expression pattern.

Multiple lines of evidence implicate numerous loci in the adaptive diversification of the Radiate morph. However, the extent to which multiple loci also assist in maintaining adaptive divergence in the Radiate metapopulation remains unclear. Current models of diversification within H. erato suggest that the Radiate phenotype evolved in the western Amazon region about 300,000 years ago and became the model for several comimetic species in the Heliconius and Eueides genera (17, 28). Yet, despite strong ecological selection favoring the Radiate morphology, extensive hybridization with non-Radiate morphs of H. erato occurs along the Andes (3). The strongest signature of genomic differentiation between hybridizing red color pattern morphs occurs around optix, and this remains true with a fixation index (Fst) of 0.66 when comparing the Radiate metapopulation data to 22 whole-genome datasets from the Postman-like metapopulation along the western side of the Andes (Fig. 1B). Examination of loci with strong signals of selection also bound by Optix, however, makes it clear that many of these regions also act as a significant engine of genomic differentiation between metapopulations.

As a case study, we looked more closely at the Optix-bound promoter of the cotranscribed domeless/washout (dome/wash) genes, which is 500 kb away from the major color-patterning gene cortex and displays the strongest signature of selection within the Radiate metapopulation (Fig. 3A). The Optix-bound dome/wash promoter was not classified as an adaptive hub, indicating that while many loci associated with selection on Optix binding sites form adaptive hubs, strong candidate loci for color patternassociated divergence are not limited to hub loci. dome has been previously implicated in multiple butterfly wing patterning roles, including yellow mimicry patterns in Heliconius (29, 30). Specifically, the study of the presence or absence of a yellow hindwing bar phenotype in H. melpomene found a significant association between single-nucleotide polymorphisms (SNPs) at the dome/wash locus and the yellow bar pattern. In crosses of Peruvian H. melpomene Radiate and Postman morph butterflies, homozygotes for the yellow hindwing bar allele were dominant over the Radiate hindwing phenotype. In H. erato, this relationship was more complicated and dependent on alleles at multiple Mendelian loci (31). Evidence of Optix binding at the dome/wash promoter and prior association with mimicry phenotypes thus suggests that optix interacts epistatically with dome/wash, although additional study of this locus will be necessary to confirm this function.

The dome/wash color-patterning locus exemplifies a strong signal of selection (A) on an Optix binding site that displays elevated population differentiation (B) and population divergence (C). Loci with strong signals of selection (selected loci) and the pigment-associated subset show increasingly significant population differentiation (D) and divergence (E) between Radiate and Postman metapopulations relative to the genome-wide distributions.

A sliding window scan of Fst, which measures within- versus between-population differentiation, showed a high degree of differentiation at the cortex locus as expected, and that differentiation decreases with distance. Fst between the Radiate and Postman metapopulations elevates again around dome/wash, with differentiation well above the 99th percentile (Fig. 3B). While selection will often lower nucleotide diversity, which, in turn, reduces the average pairwise genomic divergence between neighboring populations [e.g., (32)], any accumulated SNPs should differ between metapopulations at loci that maintain genomic separation across hybrid zones (see Supplementary Text). Therefore, we next sought to determine the extent to which the available nucleotide polymorphisms drove divergence between the Radiate and Postman metapopulations independent of within-population diversity (33). To accomplish this, we measured the nucleotide divergence between the Radiate and Postman metapopulations, normalized to the available nucleotide diversity (dxy/pi; Fig. 3C). Confirming our Fst-derived observation implicating dome/wash as a locus separating metapopulations, dxy/pi was extremely elevated (99.99th percentile) with no evidence of haplotype exchange between the metapopulations.

To investigate the genome-wide significance of this observation, we extended our analysis of metapopulation differentiation to all Optix-bound loci with strong signals of selection. Fst values were significantly greater (P < 0.001) at putative adaptive loci compared to the genome-wide distribution, with the median value in the 93rd percentile and an upper bound of 0.083 (Fig. 3D and fig. S3). dxy/pi was also strongly elevated (P < 0.001) and showed an even greater increase over the genome-wide distribution (with a median in the 97th percentile) than the relative measure of genomic differentiation (Fig. 3E). Consistent with these loci separating metapopulations, rather than solely reflecting selection, neither Fst nor dxy/pi was strongly dependent on CLR at loci with strong signatures of selection (fig. S4). Together, our results clearly demonstrate that downstream targets of Optix regulation under recent positive selection also act as moderate to strong barriers to gene flow between hybridizing morphs.

Updating the previous hypothesis for red color pattern evolution in Heliconius (34), our results now suggest a two-component model of adaptive diversification that captures the distinct processes that underlie the evolution and maintenance of red mimicry color patterns in the Radiate H. erato metapopulation: First, multigenic adaptation occurs via selection on optix, a gene with complete developmental control of red pigmentation in butterflies, and many additional loci directly regulated by changing optix expression domains (Fig. 4A). The genes associated with adaptive evolution of the Radiate morphology indicate selection on pigment composition (e.g., black and UCH), wing morphology and patterning (nkd and osa), and apparent epistatic interactions with other color pattern networks (dome/wash and Wnt signaling). In the Radiate metapopulation, selection will be a product of the relative frequency of a variant (e.g., a novel mutation versus standing genetic variation), the effect size of selected variants, and the ecological significance of the resulting phenotype. Given the very large effective population size of most Heliconius species, selection can easily act on relatively weak-effect variants to optimize even seemingly minor aspects of the Radiate morphology. While our data-driven approach cannot identify all genes associated with red color pattern evolution, we nonetheless found considerable evidence that adaptation relies on many genes in the optix network.

(A) Model showing adaptation occurs at many loci, and selection is a product of population size, the effect of a mutation, and the significance of the trait. (B) Genomic differentiation in hybrid zones is determined by both selection and the probability that a conditionally dependent allele will be functional in backcrosses. (C and D) Cartoons show phenotypes and genotypes for hybrid and pure butterflies, and potential backcross offspring broods under two scenarios of differentiation. Direct differentiation (C) of a dominant allele occurs when a hybrid individual backcrosses into the source population. Any offspring with the maladaptive allele from the hybrid parent is less fit. In conditional differentiation (D), offspring with the maladaptive dependent allele are only less fit when that individual also has the maladapted optix allele.

The Radiate phenotype is then maintained by varying degrees of genomic isolation from the Postman metapopulation (Fig. 4B) at many loci through both direct and conditional (i.e., dependent on trans-allelic effects) differentiation at loci under selection (Fig. 4, C and D). Along the Andean hybrid zone between the Radiate and Postman metapopulations, genomic differentiation begins when a hybrid individual (F1 generation) backcrosses with one of the two source populations (F0 genotypes). The backcross produces maladapted offspring subject to selection in the Radiate metapopulation if the F1 Postman color pattern alleles are transferred to the F2 offspring. Allowing for recombination to narrow maladaptive haplotypes, this results in a relatively small region that fails to pass through the hybrid zone. Similar to selection on beneficial variants, the strength of differentiation is determined by the degree of selection on the resulting phenotype but also by the likelihood of a functional allele. In the case of optix, which is functionally independent of developmentally downstream variants, 50% of F2 offspring will have the maladaptive optix allele (18, 31, 35) and strong, direct differentiation occurs (Fig. 4C).

Our results suggest, however, that conditional differentiation is also prevalent in the Radiate metapopulation along the hybrid zone. Adaptive alleles that are regulated by and functionally dependent on optix will continue to segregate at a roughly 50:50 ratio. But because these loci mostly appear on other chromosomes, maladaptive Optix-dependent haplotypes will only appear (and be subject to selection) alongside a maladaptive optix allele in 25% of F2 offspring (Fig. 4D). Genomic differentiation at Optix-dependent loci is thus conditional on allelic variation at optix itself, when in the presence of a maladaptive optix haplotype, additional downstream genetic variants from the adjacent morph will also be maladaptive. For example, genetic variants relying on Optix activation in the hindwing will have no effect in individuals without the hindwing optix expression domain. The conditional effect on differentiation is compounded in cases where dependent variants may also interact, such as implied by the synergistic effect of HDAC4 and lesswright mutant alleles on Drosophila eye pigmentation (36). Since the degree of genomic differentiation at a locus is a function of the strength of selection and likelihood of a functional allele, the combination of selection and independent segregation of alleles can produce a wide range of differentiation at adaptive loci causally linked to optix expression. This can nonetheless be a strong force for maintaining genomic separation between phenotypes.

Our current data provide some additional findings consistent with the expectations of our adaptive diversification model. Consistent with our proposal of selection on loci of varying effect size and ecological significance, selection coefficients for Optix-bound loci with strong signals of selection were generally 4- to 10-fold lower than observed at the optix locus (Fig. 5A). Similarly, our data support the view that adaptive loci that separate morphs through the process of conditional differentiation will display signatures of genomic differentiation significantly elevated above background. In our analysis, we found that Fst at 17 of 59 Optix-bound loci with strong signals of selection was at or above the 97.5th percentile (the third SD) and often much greater (Fig. 5B). Ultimately, however, additional studies of developmental function and gene flow will be necessary to rigorously test our model of adaptive diversification of the Radiate morphology.

(A) Plot shows the estimated selection coefficients derived from alpha produced by SweepFinder2; outlier from the dome/wash locus is not shown (s = 0.082). Red bar indicates the largest selection coefficient in the optix locus. (B) Evidence of moderately strong genomic differentiation at Optix-bound loci provides support for a model incorporating conditional differentiation. Orange arrowheads highlight Optix-bound loci with Fst greater than 0.04.

In this study, we show how signatures of adaptation can manifest across a gene network. To what extent might future studies expect to uncover additional genetic variation underlying trait adaptation? The mode of multigenic evolution will partly determine the propensity for both additional genetic variation and conditional differentiation. Models of classic polygenic adaptation suggest that evolution from standing genetic variation at many independent loci is a common feature of multigenic adaptive processes (37). Adaptive alleles will often be difficult to detect for classic polygenic adaptation, but none are likely to be hidden from genetic studies of trait architecture. Multiple-step adaptation, such as the proposed two-step model for Heliconius wing pattern evolution (13, 20) supported here, diverges from classic polygenic models by implicating sequential selection at multiple loci over time and is thus less limited to only ancestral variants. That is, in multistep processes, novel variants that further modify a trait might undergo a classic hard sweep, and the multigenic trait architecture would consist of both novel and ancestral alleles. In either scenario, dependency of some alleles on another locus of large effect will likely produce an effect similar to our findings here.

The ability to detect multiple loci of adaptation will also depend on the biological context of a study system. Hard sweeps are often detected by CLR methods, while soft sweeps and minor frequency shifts proposed in some polygenic models can be more difficult to detect (38, 39). Soft sweeps on rare variants, such as deleterious alleles or variants that arose just preceding the adaptive event, will often appear similar to hard sweeps (40) and can be detected with CLR methods. Multistep adaptation along a hybrid zone, as proposed here, will likely favor soft sweeps on rare variants if the subsequent selection occurs early in the diversification process. In this scenario, the initial adaptation will create a founder-like effect as the populations split and neutral variants are slowly reintroduced by gene flow. Population size variation, such as seasonal fluctuation in population size, will also increase the hardness of a sweep (39). Where adaptation occurs from older, neutral polymorphisms in response to an environmental shift, alternative methods of detecting selective sweeps may be necessary (38). Subtle shifts in allele frequencies at multiple loci is the most problematic scenario for detecting multigenic adaptation, although this is only expected when mutation rates are extremely high or the loci under selection are highly redundant with one another (41). For taxa where adaptive introgression is likely, the ability to detect introgressed sweeps will generally fall somewhere between hard and soft selective sweeps, depending on the age of the adaptive allele in the source population, the migration rate, and the origin of the new allele. In sum, tests for selection more suited to partial sweeps from neutral variation may identify additional loci associated with diversification in Heliconius butterflies and other taxa.

Ultimately, our multigenic model of adaptive diversification in Heliconius butterflies provides some resolution to the disparity between a few QTLs of large effect and the multigenic trait architecture often seen in GWAS. QTL studies from a few source individuals and scans for genomic outliers separating phenotypes will favor a few loci of large effect when additional trait-associated variants are functionally dependent on a single gene. Understanding the molecular and developmental mechanisms of adaptation can, however, bring hidden, conditional loci of adaptation to light. Thus, more detailed analysis of the mechanisms of large-effect loci will be necessary to develop a complete theory for the processes of adaptation and diversification. Future studies incorporating many more individuals will be important for understanding the complex genetic architecture of wing polymorphisms in Heliconius. Our findings, however, show that a few functional assays can substitute for hundreds or thousands of genomic samples to identify adaptive network components (42).

Genome-wide targets of Optix binding were determined using chromatin immunoprecipitation sequencing (ChIP-seq) for the Optix protein, as previously described (17). Forewing and hindwing tissue from four to six Radiate H. erato individuals of mixed sex at 3 days after pupation were used to perform the ChIP assay. Samples were taken from a laboratory colony of H. erato derived from Ecuadorian stock and kept pure for the Radiate phenotype. Samples were dissected in phosphate-buffered saline, fixed for 7 min with fresh formaldehyde, and flash-frozen on dry ice. Samples were then combined by tissue for two replicates of both forewing and hindwing assays. Chromatin from dounced and lysed samples was sheared to approximately 250 base pairs (bp) using a Bioruptor, and IP was performed overnight with a homemade Heliconius-derived Optix antibody. Input samples were taken before adding the antibody as a control. Library preparation was performed using the NEBNext Ultra II DNA library preparation kit, and both input and control libraries were sequenced on a NextSeq 500.

ChIP-seq and input control libraries were aligned to the Radiate H. erato lativitta genome assembly (43) using Bowtie 2 (44). Nonuniquely aligning reads were removed using a custom script, and data were deduplicated using picard tools. Peak calling was performed with MACS2 (45) on the paired BAM file using default settings, a genome size estimate of 3.6 108, and the input sequencing data as a control. Peak calls from forewing and hindwing samples showed a fivefold median increase over input, and 95% of ChIP peaks overlapped previously annotated sites of accessible chromatin from ATAC-seq assays of the same developmental stage (25). Comparison of forewing and hindwing samples found that, as expected, 95.4% of peaks overlapped between wing tissues, so we generated a single, high-quality ChIP peak set of 5051 Optix binding sites that were used in subsequent analyses.

Hi-C libraries used to detect Optix binding site interactions were generated using the in situ Hi-C protocol from Rao et al. (46) with minor modifications as previously described (17). Wing tissues from forewing and hindwing Radiate H. erato butterflies were prepared as described for the ChIP-seq assays. Four to five mixed-sex individuals were combined for library preparation, wing tissue was briefly dounced, and nuclei were permeabilized using 0.1% SDS. Samples were centrifuged after ligation to remove any fragments not contained within permeabilized nuclei before reverse cross-linking, and an additional step was included to reduce fragments with unligated biotin in the final libraries. Samples were sheared on a Covaris S2 sonicator, and size was selected with 1.2 AMPure beads before library preparation. Sequencing libraries were prepared with the NEBNext Ultra II DNA library preparation kit. Samples were sequenced on a NextSeq 500.

Hi-C data alignment and analysis were performed as previously described: Hi-C libraries were aligned to the H. erato lativitta genome assembly using Juicer (47). Matching our ChIP-seq analysis, alignments from all replicates were then merged to produce a final merged_nodups.txt file containing all Hi-C fragments for subsequent analyses.

To link Optix binding sites to gene TSSs, we used a two-component pipeline. All TSS-proximal ChIP-seq peaks of less than 3 kb from a potential target (generally promoter peaks) were assigned to the proximal gene TSS. We then used the hicContactCaller pipeline from Ray et al. (48) to determine the loci that interact significantly at distances greater than 3 kb compared to an empirical background model. This method calculates the observed number of reads connecting 3-kb windows around an Optix binding site (bait) to TSSs within a predesignated distance (300 kb, prey window). An empirical expected value is determined from the local Hi-C alignments, and a Fishers exact test is calculated using observed and expected read counts connecting the bait and prey loci. Interaction between the bait and prey loci were considered significant for P values of less than 0.05, as this threshold was found to be well below the 10% false discovery rate threshold in the previous study (48).

SNP calling for H. erato samples was performed as follows: Eighteen whole genome resequencing samples from three geographically adjacent H. erato Radiate populations (Radiate metapopulation: H. erato lativitta, H. erato etylus, and H. erato emma) and 22 samples from three geographically adjacent H. erato Postman populations (Postman metapopulation: H. erato favorinus, H. erato cyrbia, and H. erato notabilis) (3) were realigned to the Radiate H. erato lativitta genome assembly (43) to produce gVCF (genomic variant call format) files using GATK HaplotypeCaller with default settings (49). Populations were categorized as either Radiate or Postman, consistent with previous analyses (3). Samples included all Radiate and Postman individuals collected along the Andean hybrid zone region; Radiate and Postman individuals from geographically distant populations, such as H. erato demophoon in Panama, were excluded. SNPs were filtered using VariantFiltration with the filter MQRankSum < -12.5 || FS > 60.0 || MQ < 20.0 and called using GenotypeGVCFs. The VCF file was then additionally filtered to include only biallelic SNPs using VCFtools (50).

SweepFinder2 (51) was used to detect signatures of selective sweeps in the Radiate H. erato metapopulation. Allele counts for all biallelic Radiate sample SNPs were generated using VCFtools. SNPs were polarized using H. erato phyllis [outgroup for East Andean Radiate and Postman metapopulations (3)] whole-genome sequencing data aligned to the H. erato lativitta genome assembly (3). The ancestral allele was marked using the VCFtools fill-aa script. A custom script was then used to convert VCFtools allele counts output to the SweepFinder2 input format. SweepFinder2 was run using default settings and set to test SNPs every 2000 bp (-sg 2000).

To test for the increased selection on all Optix binding sites, the highest CLR values from the SweepFinder2 output within 2000 bp of Optix ChIP peaks were determined using bedtools (52). To prepare a control dataset, we randomly selected the same number of unbound peaks from H. erato lativitta ATAC-seq data using shuf and determined the highest CLR value within 2000 bp. This random sample was performed 10 times, then all samples were ranked from lowest to highest, and the values were averaged for each rank position to estimate the random expected value of the same number of CREs sampled from the CRE distribution in the genome. A Kolmogorov-Smirnov test was used to test for the significant difference between the expected and Optix-bound CRE distributions. The top 500 data points for each category were plotted to increase figure resolution.

To identify putatively adaptive Optix-bound loci, we designated the top 0.5% of all CLR values, equal to or greater than 63, as sites under with a strong signal of selection. We then selected all Optix-bound loci with a CLR value at or above 63 as our initial dataset. These were predominantly CRE loci but did include one gene that showed a significant selection in the gene body and was bound by Optix at the promoter. Because some highly repetitive regions show very high CLR values and were likely regions of new repeats found only in the Radiate clade, we manually curated selected loci to discard any sites where a CLR window overlapped repetitive sequences. The three major color pattern loci identified in scans of genomic differentiation were excluded from all tests for the selection on Optix-bound loci to preclude evidence of selection on the optix locus and other known loci of large effect.

To test for evidence of three-dimensional evolution associated with selection on Optix binding sites, we combined our Hi-C data with 12 RNA-seq datasets from wing tissue at 3 days after pupation (25). RNA-seq samples were collected from laboratory colonies of a Radiate morph (H. erato lativitta) and a Postman morph (H. erato petiverana). To reduce the impact of nonadaptive evolution and nonevolving loci on our results, we limited our analysis to the loci with evidence of strong selection and differentially expressed genes between Radiate and Postman phenotypes. Thus, adaptive hubs were characterized by two requirements: (i) an Optix-bound hub center meeting our definition of a strong signal of selection and (ii) Hi-Cbased evidence of physical interaction with two or more hub gene TSSs that were differentially expressed between Radiate and Postman samples. All CLR values were used to determine the genome-wide distribution of CLR values, while all TSS and adaptive hub gene loci were characterized by the highest CLR value within 2 kb, as described above. Hub centers with strong signals of selection were excluded from our analysis of selection at hub gene loci except for the few cases where two loci displaying strong signatures of selection interacted, in which case, the hub center was excluded but the interacting locus was included. Tests for significance between adaptive hub gene CLR values and control datasets were performed with a Mann-Whitney U test.

Adaptive hub genes and genes at loci with strong signals of selection were annotated using Lepbase and FlyBase. For all genes with characterized proteins or which showed some similarity to characterized proteins, gene function was manually curated. Gene annotations were categorized as pigmentation associated given (i) evidence of a known effect on pigmentation or color patterning, (ii) the gene was annotated as a regulator of known color-patterning genes in Lepidoptera (e.g., regulation of Wnt signaling), or (iii) the gene had known effects on wing morphology in Drosophila. Gene annotations were categorized as signaling, given evidence of an important role in major signaling pathways and lacking evidence of a functional role in pigmentation. All other genes were categorized as other. Detailed gene annotations are available in the Supplementary Materials.

We calculated Fst and dxy/pi to determine the extent to which loci with strong signals of selection may associate with differentiation between the Radiate and Postman metapopulations. Sliding window Fst analysis between the Radiate and Postman metapopulation samples was calculated for 20-kb intervals with 10-kb steps using VCFtools. dxy and pi were calculated for the same intervals and step size using the Genomics-General Python library (53). Statistical tests for significant deviation from the genome-wide distribution of both statistics were performed using Mann-Whitney U tests.

In addition to detecting selective sweeps, SweepFinder2 can be used to estimate selection coefficients (23, 54). To do this, we used the formula s = (r*ln(2N)) / a to estimate selection coefficients for loci with strong signals of selection. We used the previously calculated average recombination rate (r) of 1.343 107 and estimated the Radiate metapopulation size (N) at 10M or roughly twice the size of the metapopulation effective population size (23). Alpha was taken for each locus from the SweepFinder2 output. We verified our parameters by comparing our resulting selection coefficient at optix (0.0605) with a previously calculated coefficient using the same method (0.0595).

All animals were reared in accordance with institutional guidelines.

L. Livraghi, J. J. Hanly, L. S. Loh, A. Ren, I. A. Warren, C. Concha, C. Wright, J. M. Walker, J. Foley, H. Arenas-Castro, L. R. Brenes, A. Martin, W. O. McMillan, C. D. Jiggins, The gene cortex controls scale colour identity in Heliconius. bioRxiv:2020.05.26.116533 (2020).

Acknowledgments: We thank the Cornell University Insect Collection for use of the specimens to produce butterfly images. We thank K. van der Burg, L. Campagna, V. Lewis, and two anonymous reviewers for helpful comments on the manuscript. Funding: J.J.L. was supported by NASA 17-EXO-17-2-0112, NSF DEB-1546049, and NSF IOS-1656514. S.M.V.B. was supported by NSF EPSCoR RII Track-2 FEC (OIA 1736026) and, in part, by the National Institutes of Health, NIGMS COBRE Phase 2 Award, Center for Neuroplasticity at the University of Puerto Rico (grant no. 1P20GM103642). S.M.V.B. and R.P. acknowledge support from the Puerto Rico Science, Technology & Research Trust catalyzer award (grant no. 2020-00142) and NSF IOS-1656389. C.G.D. acknowledges support from the National Institutes of Health Common Fund 4D Nucleome Program (grant U01HL129958). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Author contributions: J.J.L. conceived and designed the study. J.J.L. and S.M.V.B. produced and analyzed data. C.G.D., R.D.R., and R.P. provided materials and resources. J.J.L. and S.M.V.B. interpreted the data, and all authors wrote the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: ChIP-seq, Hi-C, ATAC-seq, and RNA-seq data used in this study are available at NCBI-GEO GSE123700, GSE123701, GSE123703, GSE109889, and GSE111022. Whole-genome resequencing data are available at SRA SAMN05224096-SAMN05224211. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

See the rest here:
Many functionally connected loci foster adaptive diversification along a neotropical hybrid zone - Science Advances

Genetics

Predictive Genetic Testing and Consumer/Wellness Genomics Market set to record exponential growth by 2025-end – The Daily Chronicle

Predictive Genetic Testing and Consumer/Wellness Genomics Market: Snapshot

Genetic testing comprises examination of ones DNA. The term DNA refers to the chemical database that is responsible for conveying the instructions for functions that need to be performed by the body. Genetic testing is capable of revealing changes or mutations in the genes of living beings, which might result in any kind of disease or illness in the body.

Get Exclusive PDF Sample Copy Of This Report:https://www.tmrresearch.com/sample/sample?flag=B&rep_id=1274

Predictive genetic testingrefers to the utilization of genetic testing methods in an asymptomatic individual to make a prediction about risk of contacting particular disease in future. These tests are regarded as representation of emerging class of medical tests, which differ in fundamental ways from the usual diagnostic tests.

The global predictive genetic testing and consumer/wellness genomics marketis likely to gather momentum owing to the benefits offered by predictive genetic testing.

The benefits of predictive genetic testing are

The global predictive genetic testing and consumer/wellness genomics marketis influenced by reducing cost of genetic sequencing and technological advancement in the field of genetics. North America is expected to emerge as a prominent region for the global predictive genetic testing and consumer/wellness genomics market in years to come due to high adoption rates of latest technologies in all fields.

Over centauries human DNA has undergone tremendous alteration due to evolutionary and lifestyle changes. They have led to both, advantages and disadvantages over the years. Some have given the mankind a deserving edge over other creatures while the others have led to disorders and diseases. Predictive genetic testing and consumer/wellness genomics market thrives on the growing demand for understanding the lineage of a certain gene pool to identify disorders that could manifest in the later or early stage of a human life. The surging demand for understanding the family history or studying the nature of certain diseases has given the global market for predictive genetic testing and consumer/wellness genomics market adequate fodder for growth in the past few years.

This new class of medical tests are aimed at reducing the risk of morbidity and mortality amongst consumers. The thorough surveillance and screening of a certain gene pool can allow an individual to avoid conditions that disrupt normal existence through preventive measures. The clinical utility of these tests remains unassessed. Therefore, increasing research and development by pharmaceutical companies to develop new drugs by understanding diseases and disorders is expected to favor market growth.

Unlike conventional diagnostic testing, predictive genetic testing identifies the risk associated with potential conditions. In certain cases it is also capable of stating when the disease may appear and the how severe will it be. Thus, this form of testing is expected to allow consumers to take up wellness measurements well in time to lead a life of normalcy, characterized by good health.

Buy This Report @https://www.tmrresearch.com/checkout?rep_id=1274<ype=S

Global Predictive Genetic Testing and Consumer/Wellness Genomics Market: Overview

Predictive genetic testing are used to identify gene mutations pertaining to the disorders that surface at a considerably later stage in life after birth. These tests are particularly beneficial for people from a family with a history of genetic disorder, although they themselves show no symptoms of the disorder at the time of testing. Genetic testing promises to revolutionize the healthcare sector, providing crucial diagnostic details related to diverse verticals such as heart disease, autism, and cancer. As the healthcare sector touches new peaks, the global predictive genetic testing and consumer/wellness genomics market is projected to expand at a healthy growth rate during the forecast period of 2017 to 2025.

This report on the global market for predictive genetic testing and consumer/wellness genomics analyzes all the important factors that may influence the demand in the near future and forecasts the condition of the market until 2025. It has been created using proven research methodologies such as SWOT analysis and Porters five forces. One of the key aspect of the report is the section on company profiles, wherein several leading players have been estimated for their market share and analyzed for their geographical presence, product portfolio, and recent strategic developments such as mergers, acquisitions, and collaborations.

The global predictive genetic testing and consumer/wellness genomics market, on the basis of test type, can be segmented into predictive testing, consumer genomics, and wellness genetics. The segment of predictive testing can be sub-segmented into genetic susceptibility test, predictive diagnostics, and population screening programs, whereas the segment of wellness genetics can be further divided into nutria genetics, skin and metabolism genetics, and others.

By application, the market can be segmented into breast and ovarian cancer screening, cardiovascular screening, diabetic screening and monitoring, colon cancer screening, Parkinsons or Alzheimers disease, urologic screening or prostate cancer screening, orthopedic and musculoskeletal screening, and other cancer screening. Geographically, the report studies the opportunities available in regions such as Asia Pacific, Europe, North America, and the Middle East and Africa.

Global Predictive Genetic Testing and Consumer/Wellness Genomics Market: Trends and Opportunities

Increasing number of novel partnership models, rapidly decreasing cost of genetic sequencing, and introduction of fragmented point-solutions across the genomics value chain as well as technological advancements in cloud computing and data integration are some of the key factors driving the market. On the other hand, the absence of well-defined regulatory framework, low adoption rate, and ethical concerns regarding the implementation, are expected to hinder the growth rate during the forecast period. Each of these factors have been analyzed in the report and their respective impacts have been anticipated.

Currently, the segment of predictive genetic cardiovascular screening accounts for the maximum demand, and increased investments in the field is expected to maintain it as most lucrative segment. On the other hand, more than 70 companies are currently engaged in nutrigenomics, which is expected to further expand the market.

Global Predictive Genetic Testing and Consumer/Wellness Genomics Market: Regional Outlook

Owing to robust healthcare infrastructure, prevalence of cardiovascular diseases, and high adoptability rate of new technology makes North America the most lucrative region, with most of the demand coming from the country of the U.S. and Canada. Several U.S. companies hold patents, which further extends the outreach of the market in the region of North America.

Companies mentioned in the research report

23andMe, Inc, BGI, Genesis Genetics, Illumina, Inc, Myriad Genetics, Inc, Pathway Genomics, Color Genomics Inc., and ARUP Laboratories are some of the key companies currently operating in global predictive genetic testing and consumer/wellness genomics market. Various forms of strategic partnerships with operating company and smaller vendors with novel ideas helps these leading players maintain their position in the market.

To know more about the table of contents, you can click @https://www.tmrresearch.com/sample/sample?flag=T&rep_id=1274

About TMR Research

TMR Research is a premier provider of customized market research and consulting services to busi-ness entities keen on succeeding in todays supercharged economic climate. Armed with an experi-enced, dedicated, and dynamic team of analysts, we are redefining the way our clients conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends.

Read this article:
Predictive Genetic Testing and Consumer/Wellness Genomics Market set to record exponential growth by 2025-end - The Daily Chronicle

Anatomy

Not even Fall Guys devs can agree on the anatomy of the titular beans – Polygon

Fall Guys has been a smash success, and absolutely everyone loves the silly beans and the way they swarm across ridiculous stages in pursuit of a goal. Theres just enough in each level, like cotton candy landscapes and giant, silly billboards, to ignite fans imagination about the world. And they want answers to the difficult questions. Specifically, how do these Fall Guys live, and what, exactly, do they look like?

Well, it turns out that not even the developers at Mediatronic are sure, especially in light of several recent tweets.

Senior concept artist Tudor Morris provided a sketch on Twitter, which suggests that every single Fall Guy is stuffed with a giant, spooky skeleton. I dont like this very much! Morris wrote the following explanation on his Instagram, which may either soothe or further unsettle players.

You have have options for how you interpret this, but I refuse to comment to elaborate:

1) This was a lunchtime sketch that has no meaning and was done as a joke

2) This is a canonical representation of whats inside a fall guy, we knew from the start that they werent as marketable like this so we gave them nice little cuddly suits.

The important thing to bear in mind is that, whatever the interpretation you take away, they are very happy little beans.

Well! Its good to know that these beans are happy, because it simply wouldnt do if they were miserable while they chased eggs and jumped on brightly colored hexagons. Meanwhile, principal concept artist Ash Kerins has a much sunnier view on the anatomy of each little bean, which also showed up on Twitter.

The developers arent the only one who have speculated about the origin and creation of the Fall Guys. Fan artists online are also up to the task, coming up with many ways that these beans are assembled and prepared for a life of eternal platforming combat. What if theyre not born... but created?

Another Tweet suggests that the Fall Guys could be like towering mechas, ready for combat.

Even the games publisher, Devolver Digital, got in on the wild speculation train by quote-tweeting a piece of art back in August. Devolver quote tweeted a gif of the Fall Guys being ground into the goo that shows up on maps like Slime Climb.

This is canon, they wrote, with an air of finality that they have not earned. Please respect our decision.

We may never know the truth behind these mysterious beans or why theyre so hungry for crowns. Even Mediatronic and Devolver seem to disagree with several key points of this games mythos. Perhaps the upcoming season 2 will answer some questions, but it might just increase the mystery.

Here is the original post:
Not even Fall Guys devs can agree on the anatomy of the titular beans - Polygon

Anatomy

The Anatomy of Arabesque: Why Placement and Turnout Are Key to Achieving This Crucial Position – pointemagazine.com

Training Grounds

Melendez was born and raised in Tampa, Florida, where she danced from age 4 at a small recreational studio. "I did everything from ballet to contemporary, jazz to acro," says Melendez. At 8, she switched to All American Dance Factory and Classical Ballet School, studying and competing in the standard comp-kid fare of jazz, acro, contemporary and hip hop. Yet Melendez found herself drawn to ballet's clear structure. "My first ballet competition was Youth America Grand Prix in 2011," she remembers. "I did it on flat because that was my first year on pointe." Before long, she became a regular in the top five at ADC|IBC, World Ballet Competition, YAGP and New York City Dance Alliance.

Melendez says there wasn't any one lightbulb moment that made her realize ballet was her dream. But that doesn't mean the ballet world wasn't taking notice of her. In 2015, the Ballet West Academy had already offered 15-year-old Tatiana admission to their year-round program when she was spotted at ADC|IBC by Houston Ballet II's ballet master Claudio Muoz, who was judging. "My eyes went right to Tatiana, because her jumps and turns had phenomenal energy," Muoz recalls. That "raw, incredible talent" netted Melendez a full scholarship to the Professional Program at Houston Ballet Academy. After taking time to consider Houston Ballet's rep (contemporary-leaning), her connection with Muoz (strong and encouraging), and friends' testimonials about the year-round program (glowing), Melendez moved into student housing.

In Houston, Melendez saw no shortage of stage time. She was cast in The Nutcracker and Stanton Welch's Cinderella, on top of all her academy performances. She was also one of a few academy dancers picked by company member Oliver Halkowich for his contemporary piece Full Circle.

Between shows, she worked hard. "At my competition studio, we never had pas de deux or full pointe classes," Melendez says. "The grueling academy schedule really polished my technique." Muoz says that in just two years Melendez transformed her own dancing: "Tatiana is the most incredible hard worker I ever saw. She became a beautiful swan, with a classical heart and contemporary soul."

Going Pro, With Cons

After graduation, Melendez headed to Fort Worth, where she'd landed a trainee contract with Texas Ballet Theater. It was a tough transition. "I went from training all day every day, to one morning class followed by standing on the side during hours of rehearsal," she says. Melendez's gifts were far from ignored, though. As a trainee, she danced in the corps of productions like Swan Lake and Beauty and the Beast, was one of six lead women in Ben Stevenson's world premiere Martinu Pieces, and led multiple performances of The Nutcracker as Clara.

At the end of the season, however, Melendez's worst nightmare came true. Her contract was not renewed because, at 5' 1", she was considered too short for the company. "My height had always been an insecurity," Melendez says. "Once, at a ballet competition, someone told me as I came offstage that I would never make it because I'm 'not built for dance.' "

From left: Candy Tong, Melendez and Eriko Sugimura in Dwight Rhoden's Love Rocks

Justin Chao, Courtesy Complexions Contemporary ballet

Disappointed, Melendez threw herself into auditioning for classically based companiesonly to be told over and over that, while her technique was great, her size was a nonstarter. "Being told 'no' so many times was really discouraging, because my height is something I can't change," she says. Melendez had even started talking herself into taking a year off from dance when she decided at the last minute to attend Complexions' open call in New York City. "Complexions was always a dream in the back of my head, but I never thought it'd be attainableit wasn't even on my list of places to audition," she remembers.

Taking Flight

Thus began what Melendez calls the hardest, happiest two days of her life. More than 400 dancers showed up to the Complexions' open call in April 2018, but after technique classes and "the fastest I've had to learn choreography, ever," Melendez made it all the way through the final cut. By the end of the two nonstop days, she felt sure that Rhoden's daring, athletic contemporary movement was her true callingbut still assumed she wouldn't get the job.

She needn't have worried. As Desmond Richardson, Complexions' co-founder and co-artistic director says, "Tatiana clearly made her presence known from the moment she walked through the door. I remember Dwight and I saying, 'Wow, she's really something.' Her professionalism, her innate sense of musicality and the sheer force of her were quite nostalgic to me." Rhoden adds, "What made Tatiana stand out was her fearlessness. She applied corrections, dynamics and ideas immediately in the audition. She knows how to cross the t's and dot the i's."

Simon Plant and Melendez performing Dwight Rhoden's WOKE

Stephen Pisano, Courtesy Complexions Contemporary Ballet

Melendez says that joining Complexions was a complete 180, in the best way possible. Because the company is made up of just 17 dancers, she and other new members were immediately thrown into learning repertoire, performing across the country and internationally, and collaborating with Rhoden in the studio. "Working with Dwight one-on-one is incredible," she says. "Performing choreography actually made on you, using your strengths, is so satisfying. Especially in this work called WOKE that's about issues of social justice, I've really had to dig deep and bring a different dancer out from within myself."

Though she's occasionally felt homesick for the classics, Melendez believes that dancing with Complexions allows her to dance as the fully mature version of herself. "As much as Clara was a fun role, and as much as I love watching classical ballet, I don't want to always be typecast as a little girl," she explains.

After a season and a half of whirlwind touring (so far to New Zealand, Europe and throughout the U.S.) and intense creative process, Melendez's newfound routine with Complexions has sadly been put on pause in the age of the coronavirus. At home in Tampa with family, she has used the hiatus to pursue her other creative passions of drawing and photography, and to teach Complexions rep as part of the company's virtual offerings. Melendez is looking forward to getting back to work with Complexions, and to continued guest appearances with classical companies, like Italy's Roma City Ballet. "Growing up, I thought I had to focus on just ballet or just contemporary if I wanted to be good," she says. "Now I see that having kept my feet in both worlds will help me dance as many roles as I can for as many choreographers as I can to the fullest capacity I canwhich is all I've ever wanted to do." We'd like to see someone try to stop her.

See the rest here:
The Anatomy of Arabesque: Why Placement and Turnout Are Key to Achieving This Crucial Position - pointemagazine.com

Anatomy

Long Trends and Disruption: The Anatomy of the ‘Post World’ of the Covid-19 Crisis – Valdai Discussion Club

What will be the economic architecture of the world after the Covid-19 crisis? This question involves understanding the major trends at work for twenty years now.

The world that will emerge from this crisis will be marked by these major trends, which, for some, will be reinforced by this crisis. However, this crisis has created too specific disruptions, in particular in the field of transport and energy. It has also provoked an awareness of the centrality of sovereignty, and in particular of economic sovereignty. Finally, the economic and monetary policies that have been put in place to combat the economic effects of the epidemic and of containment will have long-term consequences on international financial balances.

An acceleration of the change of the world?

Since 2000, we have witnessed the rise of an Asian bloc to the detriment of what we might call the Western bloc, that is to say the United States, the European Union and the United States. Japan. This Asian bloc is heterogeneous, as is the Western bloc. In each of these bloc politics is the main factor of homogeneity. But, these blocs also correspond to an economic reality: that of the countries of old industrialization against the countries, which it is better to call new industrialization than emerging ones.

Graph 1

Source: IMF, World Economic Outlook database

During his long tenure as Prime Minister of Japan, Abe managed to formulate his own foreign policy strategy and take measures to implement it. In addition, the Abe administration was characterised by an unprecedented concentration of power in the hands of the prime minister, his advisers and the administration. The high stability of power and great foreign policy activity made Abe one of the most recognisable and respected politicians in the international arena.

In 2000, the China-India-Russia combined represented only 15% of world GDP, while the United States, the European Union and Japan combined weighed more than 47%, or three times as much. In 2020, the two blocks are tied at around 31.5%. If we take into account the immediate effects of the Covid-19 crisis, this movement is even expected to grow. The IMF has made forecasts which indicate that China and emerging countries should recover much faster from the shock of this crisis than the so-called "advanced" countries, ie countries of former industrialization. The world should see the shift to Asia amplify in the coming years.

Graph 2

Source: IMF staff estimates

The death of oil has been greatly exaggerated (bcc, Mark Twain)

The Covid-19 pandemic has had a profound influence on the energy market and on oil production. The persistence of the pandemic means that air transport, among other things, will not return to its 2019 level before, no doubt, 2024. This implies a weak demand for kerosene as estimated by the International Energy Agency Forecasts of global oil demand and post-crisis economic growth are determined by different assumptions. In the optimistic scenario, there is a rapid economic recovery in a more or less flattened "V" shape in the first half of 2021, but the demand for oil does not fully return to the pre-pandemic trend. In the more pessimistic scenario, oil demand will not reach 2019 levels until 2023, and its growth will remain well below the pre-pandemic trend. The current evolution of the pandemic suggests that we are closer to this pessimistic scenario. These two scenarios also assume that zero-emission vehicles will represent 60% of new vehicle sales by 2040, because investments are high in these technologies. Therefore, they both forecast a slowdown in demand for oil to peak in the mid-2030s at around 105-108 Mb/d. What will be the consequence?

In the medium term, OPEC will have to manage the probable return of part of the 5.7 Mb / d of unused production in OPEC countries (Venezuela, Iran and Libya) and non-OPEC countries (Syria and Yemen). ). OPEC will also have to deal with the resumption of US hydrocarbon production (particularly shale oil), a recovery that may be slow due to falling investment, as demand and the price of oil rise. US production of hydrocarbons has fallen by more than 2 billion barrels / days, due to the closure of existing wells, reduced storage capacity and reduced demand.

The impact of Covid-19 on oil demand will therefore be profound, particularly in the event of a deep and long recession associated with a protracted pandemic. Without aggressive intervention by OPEC, the average crude oil price could thus remain below $ 50 / barrel until mid-2022. During the second half of this decade, supply and demand are expected to move closely towards equilibrium as non-OPEC production, especially from Russia, begins to decline and US hydrocarbon production reaches a low. tray. The price of oil is expected to rise to around $ 80-90 / barrel (optimistic scenario) or $ 70-80 / barrel (pessimistic scenario), even without OPEC intervention.

As we can see, however, despite all voluntarist proclamations one can hear here and there, oil will remain a major source of energy for at least the next thirty years.

The return of economic sovereignty

A more direct change brought about by the Covid-19 pandemic is the realization of the importance of economic sovereignty. Of course, a number of countries, China, Russia, but also the United States and India, were acutely aware of the importance of this sovereignty. The European Union, for its part, had adopted a very negligent attitude on this subject. The strong disruption of international trade caused by the pandemic caused a real shock on this point. Of course, there is no question of returning to more or less self-sufficient economies. But, the economic, social, and even strategic damage caused by free trade policies are globally more taken into account today.

This will accelerate the return of nations and the crisis of multilateralism that we could already observe. The economy is once again becoming a breeding ground for strategy. Through the policy of economic sanctions, which the United States has used and abused since well before the election of Donald Trump, we are witnessing an acceleration of the fragmentation of the world economic space. American pressure on Huawei, or on the Chinese social network "TikTok" is an example. De-globalization had passed from the stage of possibility to that of concrete fact; with the effects of the pandemic it will pass from that of fact to that of major fact.

This return to economic sovereignty induces the great revenge of politics over "technology", the triumph of decisions over the automaticity of standards. However, " technology" is embodied today mainly in economics and finance. The pandemic heralds the return of sovereignty, and being sovereign is above all having the ability to decide. The countries will then be referred to logic of bilateral relations, or even to regional logic. It will then be necessary to seek allies.

The questioning of the "global" character of the companies linked to the INTERNET, the desire of several countries to build their "digital sovereignty" is an example of the struggle that is looming for economic sovereignty. This resurgence of politics does not mean that, in our societies, certain spaces are not governed by the technical order, and that there are spaces dominated by technical legitimacy. But, these dimensions will now become second in relation to the political, which will recover its rights.

Originally posted here:
Long Trends and Disruption: The Anatomy of the 'Post World' of the Covid-19 Crisis - Valdai Discussion Club

Anatomy

Anatomy Of A Scandal is being adapted into a Netflix TV show – Cosmopolitan UK

If there's one thing Netflix is good at (er, they're good at lots of things actually), it's adapting best selling books in TV shows. They did it with Mindhunter; they did it with You, and now they're doing it with Anatomy Of A Scandal.

The book by Sarah Vaughan, which came out in January 2018, tells the story of a high profile couple, whose marriage begins to unravel when he's accused of a heinous crime. Barrister Kate is prosecuting the case, and is not only convinced James is guilty, but also determined he'll go down. It's SUCH a good thriller. Here's everything you need to know about the Netflix adaptation, from release date to cast:

In September 2020, Deadline first announced an adaptation was in the works. Their report revealed Big Little Lies creator David E. Kelley and former House Of Cards showrunner Melissa James Gibson were collaborating to create the series, which will be directed by S.J. Clarkson of Succession and Jessica Jones fame.

The series will be six episodes, each lasting one hour.

Anatomy of a Scandal

6.55

Now this is mainly why we're so excited. The cast is STELLAR.

Sienna Miller will play Sophie, the Oxford graduate and mother of two who has her seemingly perfect life turned upside down by the scandal surrounding her husband, James.

Rupert Friend from Homeland and The Boy In The Striped Pyjamas will play James, the handsome, privileged and charismatic man, who works as a Westminster politician.

As for 'steely' Kate? Downtown Abbey's Lady Mary Crawley aka Michelle Dockery will take on the role of the barrister, who is experienced in sexual assault cases and sees this as the career move of a lifetime.

Getty Images

Hard to know. Filming in London hasn't yet begun, given the filming restrictions caused by coronavirus lockdown, so we could have a while to wait. But worth it!

Like this article? Sign up to our newsletter to get more articles like this delivered straight to your inbox.

SIGN UP

This content is created and maintained by a third party, and imported onto this page to help users provide their email addresses. You may be able to find more information about this and similar content at piano.io

Read more here:
Anatomy Of A Scandal is being adapted into a Netflix TV show - Cosmopolitan UK

Anatomy

10 Pop Hits That Could Be ‘Grey’s Anatomy’ Episode Titles – TV Insider

Every single Greys Anatomy episode shares its name with a song titleeven 1-800-799-7233, the episode named after the National Domestic Violence Hotline.

So with that in mind, weve combed the current Billboard Hot 100 for pop hits that could be the namesakes for Season 17 episodes, and weve even dreamt up loglines for these imagined episodes. (Dont worrywere not going anywhere near WAP.)

In the (imagined) series premiere, Grey Sloan is overloaded by coronavirus patients and victims of one of the many wildfires impacting the Pacific Northwest.

Owen (Kevin McKidd) and Teddy (Kim Raver) finally have it out over her pre-wedding hookup with Koracick (Greg Germann), and in so doing, they reopen old wounds from their years of romantic strife.

Richard (James Pickens Jr.) and Catherine (Debbie Allen) are exposed to COVID-19 at one of his physical therapy sessions, and as they quarantine together for two weeks, they reach a verdict about their relationship.

Jessica Brooks/ABC

When they scrub in on a marathon operation, Meredith (Ellen Pompeo) helps Jo (Camilla Luddington) process Alexs abrupt departure, sharing from personal experience that there is love after The One.

Link (Chris Carmack) realizes hes out of his depth with a complicated orthopedic case, so sends Catherines private jet to NYC to pick up Grey Sloans original ortho god: one Calliope Iphegenia Torres (Sara Ramirez).

This years batch of Catherine Fox Award nominees include multiple Grey Sloan docs as well as Arizona Robbins (Jessica Capshaw) and Nicole Herman (Geena Davis).

Sparks flyliterally and figurativelywhen Schmitt (Jake Borelli) tags along on an all-night rescue mention with strapping Station 19 firefighter Travis Montgomery (Jay Hayden).

Kelsey McNeal/ABC

Maggie (Kelly McCreary) and Hayes (Richard Flood) embark on a rare heterotopic heart transplant on a toddler, piggybacking a donor heart onto their young patients original heart.

Meredith, preoccupied with the prospect of developing Alzheimers like her mother did, teams up with Amelia (Caterina Scorsone) to test an experimental preventative treatment involving flickering light.

A cabin depressurization aboard a jetliner sends scores of passengers with ruptured eardrums to Grey Sloan. (Sorry! We had to!)

Greys Anatomy, Season 17 Premiere, Thursday, November 12, 9/8c, ABC

Read the rest here:
10 Pop Hits That Could Be 'Grey's Anatomy' Episode Titles - TV Insider

Anatomy

Scarlet Witch: The Mystical Avenger Has Marvel’s Wildest Powers and History – CBR – Comic Book Resources

The Scarlet Witch has gone through a litany of changes throughout both her comic book and MCU career that showcase how unique and boundless she is.

Elizabeth Olsen's portrayalof Wanda Maximoff in the Marvel Cinematic Universe has seen Scarlet Witch's popularity skyrocket. Like other heroes in the Marvel Universe, she has particularly unique skills and anatomy, all of which have factored into her progression as a character.

Scarlet Witch was created by Stan Lee and Jack Kirby and first appeared in 1964'sX-Men #4. Wanda has always been an incredibly complex character full of rich storylines that delve deep into her personal relationships with her twin brother,husband and children, buther notable appearances in Avengers:Infinity War and Endgame didn't have nearly enough time to do anything but paraphrase her odd family bonds.

However, her MCU appearances did showcase Wanda's supreme ability and outright power on a battlefield. Still, her scenes didn't scratch the surface of her real power. Scarlet Witch has gone through a litany of changes throughout both her comic book and MCU career that showcase how unique and boundless this protagonist truly is.

RELATED: Captain America: Sharon Carter Realizes What Her Greatest Strength Is

Wanda and her twin brother Pietroare commonly referred to asmutants, but their powers and abilities have a much more complicated origin. Their powers come from the demon Chthon and were manipulated by the High Evolutionary.

The High Evolutionary played an instrumental role in Wanda's path to becoming the Scarlet Witch. High Evolutionary's claim to fame is the serum that allows him to manipulate and unlock the human genetic code. He decided to build a futuristic citadel in Transia on the Wundagore Mountain to conduct his experiments. While he was trying to cure his lycanthropy with dark magic, he summoned an ancient demon known as Chthon.

Herbery banished the demon but he found traces of its power remaining in a pair of twin infants that were born on themountain --Wanda and Pietro.The High Evolutionary experimented on the twins. Their Chthon influence offered him a window into its world and he wanted to tap into its raw power. However, his experiments were unsuccessful and he left the children with a Romanicouple who had lost their own children.

Related:SWORD: Marvel Ties X of Swords to Empyre with a New Series

Wanda eventually fell in love with Vision in the seminal storyVision and the Scarlet Witch by Bill Mantlo, Rick Leonardi, Ian Akin, Brian Garvey, George Roussos and Janice Chiang. Billy and Tommy are referred to as Vision and Scarlet Witch's children, but theywere in no way conceived in a conventional way.

Tommy and Billy are missing shards of a demon brought to life with Wanda's magic. At one point, the children are reabsorbed by the demon they come from, but are reincarnated into their current forms of Wiccan and Speed. Wiccan shares his mother's powers, while Speed has identical powers to his uncle Quicksilver.

Wanda unleashed the full of extent of her chaos magic and it created a reality-altering event known as the House of M, byBrian Michael Bendis, Olivier Coipel, Tim Townsend, and Frank D'Armata.Wanda has a mental breakdown and uses her massive power to change reality so she can get her children back.

This alternate reality sees Magneto and the mutants rise to take control of the world. The X-Men and Avengers join forces to reverse the reality-altering Chaos magic. These events were incredibly impactful and led directly into the Secret Wars events.

RELATED: Thanos vs. Scarlet Witch: Who Would Win?

Chthon actually came back and possessed Wanda a couple of times. The most recent possession happened during Secret Empire,by Nick Spencer, Rod Reis, Joshua Cassara, Leinil Francis Yu, Gerry Alanguilan, Rachelle Rosenberg, Sunny Gho and Travis Lanham. Hydra uses Chthon to possess Wanda and turn her against the Avengers. It's actually Wanda's former fianc, Doctor Doom, who frees her from Chthon's grip so she canrejoin the Avengers.

Wanda Maximoff's MCU origin shares important similarities to her comic book beginnings, but it hasone major difference. Both versions of Wanda's character were heavily influenced and involved in the political turmoil sweeping her country. After her parents were killed by Stark weapons, she and her twin brother swore to get their revenge, which eventually led to her involvement with the Avengers.

However, Wanda's powers in the MCU weren't created by a demon's magic but an Infinity Stone:The Space Stonem,aka the Tesseract. Wanda and her brother signed up for radical experimentation to end the war in her country of Sokovia. These experiments led to the birth of their extreme powers. While Pietro doesn't make it out of Avengers: Age of Ultron,the Scarlet Witch becomes a staple member of the franchise.

KEEP READING: WandaVision: Reality Comes Apart in Disney+ Series' First Trailer

Hellboy and the BPRD Is the Perfect Blueprint for Prequels

Jonathan Olsen-Koziol has been training for this his entire life. Since he was a young child he's been consuming and studying comic books, movies, video games, heroes, villains, story arcs, and pop-culture. Now he gets to relay a lifetime of passion and knowledge to the people! If his writings find you; hopefully you leave entertained. Jon graduated from Central Washington University with a Bachelor's in journalism and concurrently works as a head editor and digital content specialist for RespectMyRegion.com.

Here is the original post:
Scarlet Witch: The Mystical Avenger Has Marvel's Wildest Powers and History - CBR - Comic Book Resources

Genetics

Genetic analysis finds link between obesity-related genes and rheumatoid arthritis – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Sep 23 2020

An analysis of genetic data collected from more than 850,000 individuals of European ancestry has found a link between obesity-related genes and rheumatoid arthritis.

In the Arthritis & Rheumatology analysis, investigators found an increased risk of rheumatoid arthritis when body mass index was predicted to be high based on an individual's genetics. This was observed for both men and women.

These results highlight an important role of obesity in the pathological development of rheumatoid arthritis, as well as provide a potential actionable preventive strategy. Future studies are needed to understand the biological mechanisms underlying such a link, and to understand how obesity may causally influence rheumatoid arthritis prognosis."

Xia Jiang, PhD, Senior Author, Karolinska Institute, Sweden

Source:

Journal reference:

Tang, B., et al. (2020) Obesityrelated traits and the development of rheumatoid arthritis evidence from genetic data. Arthritis & Rheumatology. doi.org/10.1002/art.41517.

Visit link:
Genetic analysis finds link between obesity-related genes and rheumatoid arthritis - News-Medical.Net