scholarly journals The analysis of epigenomic evolution

2021 ◽  
Author(s):  
Arne Sahm ◽  
Philipp Koch ◽  
Steve Horvath ◽  
Steve Hoffmann
Keyword(s):  
Binding Sites ◽  
Phylogenetic Trees ◽  
Phylogenetic Reconstruction ◽  
Systematic Investigation ◽  
Data Set ◽  
Evolutionarily Conserved ◽  
Immune Related Genes ◽  
Genomic Regions ◽  
Blood Data

While the investigation of the epigenome becomes increasingly important, still little is known about the long-term evolution of epigenetic marks and systematic investigation strategies are still withstanding. Here, we systematically demonstrate the transfer of classic phylogenetic methods such as maximum likelihood based on substitution models, parsimony, and distance-based to interval-scaled epigenetic data (available at Github). Using a great apes blood data set, we demonstrate that DNA methylation is evolutionarily conserved at the level of individual CpGs in promotors, enhancers and genic regions. Our analysis also reveals that this epigenomic conservation is significantly correlated with its transcription factor binding density. Binding sites for transcription factors involved in neuron differentiation and components of AP-1 evolve at a significantly higher rate at methylation than at nucleotide level. Moreover, our models suggest an accelerated epigenomic evolution at binding sites of BRCA1, CBX2, and factors of the polycomb repressor 2 complex in humans. For most genomic regions, the methylation-based reconstruction of phylogenetic trees is at par with sequence-based reconstruction. Most strikingly, phylogenetic reconstruction using methylation rates in enhancer regions was ineffective independently of the chosen model. We identify a set of phylogenetically uninformative CpG sites enriching in enhancers controlling immune-related genes.

Can the Cambrian explosion be inferred through molecular phylogeny?

Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 15-25
Author(s):  
Hervé Philippe ◽  
Anne Chenuil ◽  
André Adoutte
Keyword(s):  
Phylogenetic Trees ◽  
18S Rrna ◽  
Phylogenetic Reconstruction ◽  
Cambrian Explosion ◽  
Bootstrap Support ◽  
Time Interval ◽  
Short Time Interval ◽  
Data Set ◽  
Molecular Phylogenetic ◽  
Animal Phyla

Most of the major invertebrate phyla appear in the fossil record during a relatively short time interval, not exceeding 20 million years (Myr), 540-520 Myr ago. This rapid diversification is known as the `Cambrian explosion'. In the present paper, we ask whether molecular phylogenetic reconstruction provides confirmation for such an evolutionary burst. The expectation is that the molecular phylogenetic trees should take the form of a large unresolved multifurcation of the various animal lineages. Complete 18S rRNA sequences of 69 extant representatives of 15 animal phyla were obtained from data banks. After eliminating a major source of artefact leading to lack of resolution in phylogenetic trees (mutational saturation of sequences), we indeed observe that the major lines of triploblast coelomates (arthropods, molluscs, echinoderms, chordates...) are very poorly resolved i.e. the nodes defining the various clades are not supported by high bootstrap values. Using a previously developed procedure consisting of calculating bootstrap proportions of each node of the tree as a function of increasing amount of nucleotides (Lecointre, G., Philippe, H. Le, H. L. V. and Le Guyader, H. (1994) Mol. Phyl. Evol., in press) we obtain a more informative indication of the robustness of each node. In addition, this procedure allows us to estimate the number of additional nucleotides that would be required to resolve confidently the currently uncertain nodes; this number turns out to be extremely high and experimentally unfeasible. We then take this approach one step further: using parameters derived from the above analysis, assuming a molecular clock and using palaeontological dates for calibration, we establish a relationship between the number of sites contained in a given data set and the time interval that this data set can confidently resolve (with 95% bootstrap support). Under these assumptions, the presently available 18S rRNA database cannot confidently resolve cladogenetic events separated by less than about 40 Myr. Thus, at the present time, the potential resolution by the palaeontological approach is higher than that by the molecular one.

scholarly journals Flexible Mixture Model Approaches That Accommodate Footprint Size Variability for Robust Detection of Balancing Selection

2020 ◽  
Vol 37 (11) ◽  
pp. 3267-3291 ◽  
Author(s):  
Xiaoheng Cheng ◽  
Michael DeGiorgio
Keyword(s):  
Pain Perception ◽  
Balancing Selection ◽  
Genomic Data ◽  
Composite Likelihood ◽  
Ratio Test ◽  
Data Set ◽  
Robust Detection ◽  
Population Genomic ◽  
Genomic Regions

Abstract Long-term balancing selection typically leaves narrow footprints of increased genetic diversity, and therefore most detection approaches only achieve optimal performances when sufficiently small genomic regions (i.e., windows) are examined. Such methods are sensitive to window sizes and suffer substantial losses in power when windows are large. Here, we employ mixture models to construct a set of five composite likelihood ratio test statistics, which we collectively term B statistics. These statistics are agnostic to window sizes and can operate on diverse forms of input data. Through simulations, we show that they exhibit comparable power to the best-performing current methods, and retain substantially high power regardless of window sizes. They also display considerable robustness to high mutation rates and uneven recombination landscapes, as well as an array of other common confounding scenarios. Moreover, we applied a specific version of the B statistics, termed B2, to a human population-genomic data set and recovered many top candidates from prior studies, including the then-uncharacterized STPG2 and CCDC169–SOHLH2, both of which are related to gamete functions. We further applied B2 on a bonobo population-genomic data set. In addition to the MHC-DQ genes, we uncovered several novel candidate genes, such as KLRD1, involved in viral defense, and SCN9A, associated with pain perception. Finally, we show that our methods can be extended to account for multiallelic balancing selection and integrated the set of statistics into open-source software named BalLeRMix for future applications by the scientific community.

scholarly journals Genome-wide reconstruction of rediploidization following autopolyploidization across one hundred million years of salmonid evolution

2021 ◽  
Author(s):  
Manu Kumar Gundappa ◽  
Thu-Hien To ◽  
Lars Grønvold ◽  
Samuel A M Martin ◽  
Sigbjørn Lien ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Sequence Divergence ◽  
Meiotic Pairing ◽  
Genome Wide ◽  
A Genome ◽  
Clock Analysis ◽  
Multiple Species ◽  
Genomic Regions ◽  
Genome Assemblies

The long-term evolutionary impacts of whole genome duplication (WGD) are strongly influenced by the ensuing rediploidization process. Following autopolyploidization, rediploidization involves a transition from tetraploid to diploid meiotic pairing, allowing duplicated genes (ohnologues) to diverge genetically and functionally. Our understanding of autopolyploid rediploidization has been informed by a WGD event ancestral to salmonid fishes, where large genomic regions are characterized by temporally delayed rediploidization, allowing lineage-specific ohnologue sequence divergence in the major salmonid clades. Here, we investigate the long-term outcomes of autopolyploid rediploidization at genome-wide resolution, exploiting a recent 'explosion' of salmonid genome assemblies, including a new genome sequence for the huchen (Hucho hucho). We developed a genome alignment approach to capture duplicated regions across multiple species, allowing us to create 121,864 phylogenetic trees describing ohnologue divergence across salmonid evolution. Using molecular clock analysis, we show that 61% of the ancestral salmonid genome experienced an initial 'wave' of rediploidization in the late Cretaceous (85-106 Mya). This was followed by a period of relative genomic stasis lasting 17-39 My, where much of the genome remained in a tetraploid state. A second rediploidization wave began in the early Eocene and proceeded alongside species diversification, generating predictable patterns of lineage-specific ohnologue divergence, scaling in complexity with the number of speciation events. Finally, using gene set enrichment, gene expression, and codon-based selection analyses, we provide insights into potential functional outcomes of delayed rediploidization. Overall, this study enhances our understanding of delayed autopolyploid rediploidization and has broad implications for future studies of WGD events.

Configurations to Superior Environmental Innovation Strategy: A Both–And Approach

2021 ◽  
pp. 108602662110316
Author(s):  
Tiziana Russo-Spena ◽  
Nadia Di Paola ◽  
Aidan O’Driscoll
Keyword(s):  
Climate Change ◽  
Value Chain ◽  
Critical Role ◽  
Well Being ◽  
Point Of View ◽  
Future Generations ◽  
Innovation Strategy ◽  
Environmental Innovation ◽  
Data Set

An effective climate change action involves the critical role that companies must play in assuring the long-term human and social well-being of future generations. In our study, we offer a more holistic, inclusive, both–and approach to the challenge of environmental innovation (EI) that uses a novel methodology to identify relevant configurations for firms engaging in a superior EI strategy. A conceptual framework is proposed that identifies six sets of driving characteristics of EI and two sets of beneficial outcomes, all inherently tensional. Our analysis utilizes a complementary rather than an oppositional point of view. A data set of 65 companies in the ICT value chain is analyzed via fuzzy-set comparative analysis (fsQCA) and a post-QCA procedure. The results reveal that achieving a superior EI strategy is possible in several scenarios. Specifically, after close examination, two main configuration groups emerge, referred to as technological environmental innovators and organizational environmental innovators.

EXPRESS: How Does Bonus Payment Affect the Demand for Auto Loans and Their Delinquency?

2021 ◽  
pp. 002224372110092
Author(s):  
Zhenling Jiang ◽  
Dennis J. Zhang ◽  
Tat Chan
Keyword(s):  
Consumer Products ◽  
Data Set ◽  
Financial Decisions ◽  
Consumer Panel ◽  
Loan Demand ◽  
Bonus Payments ◽  
Base Salary ◽  
Long Term Impact ◽  
Shed Light

This paper studies how receiving a bonus changes the consumers’ demand for auto loans and the risk of future delinquency. Unlike traditional consumer products, auto loans have a long-term impact on consumers’ financial state because of the monthly payment obligation. Using a large consumer panel data set of credit and employment information, the authors find that receiving a bonus increases auto loan demand by 21 percent. These loans, however, are associated with higher risk, as the delinquency rate increases by 18.5 −31.4 percent depending on different measures. In contrast, an increase in consumers’ base salary will increase the demand for auto loans but not the delinquency. By comparing consumers with bonuses with those without bonuses, the authors find that bonus payments lead to both demand expansion and demand shifting on auto loans. The empirical findings help shed light on how consumers make financial decisions and have important implications for financial institutions on when demand for auto loans and the associated risk arise.

scholarly journals A machine learning case–control classifier for schizophrenia based on DNA methylation in blood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chathura J. Gunasekara ◽  
Eilis Hannon ◽  
Harry MacKay ◽  
Cristian Coarfa ◽  
Andrew McQuillin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Population Based ◽  
Case Control ◽  
Training Data ◽  
Polygenic Risk Score ◽  
Reverse Causality ◽  
Cell Type Specificity ◽  
Data Set ◽  
Human Genomic ◽  
Genomic Regions

AbstractEpigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case–control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported. Using the first two SPLS-DA dimensions we calculated a “risk distance” to identify individuals with the highest probability of SZ. The model was then evaluated on an independent HM450 data set on 353 SZ cases and 322 non-psychiatric controls. Our CoRSIV-based model classified 303 individuals as cases with a positive predictive value (PPV) of 80%, far surpassing the performance of a model based on polygenic risk score (PRS). Importantly, risk distance (based on CoRSIV methylation) was not associated with medication use, arguing against reverse causality. Risk distance and PRS were positively correlated (Pearson r = 0.28, P = 1.28 × 10−12), and mediational analysis suggested that genetic effects on SZ are partially mediated by altered methylation at CoRSIVs. Our results indicate two innate dimensions of SZ risk: one based on genetic, and the other on systemic epigenetic variants.

scholarly journals Principals between exploitation and exploration: Results of a nationwide study on ambidexterity of school leaders

2020 ◽  
pp. 174114322094570
Author(s):  
Marcus Pietsch ◽  
Pierre Tulowitzki ◽  
Colin Cramer
Keyword(s):  
Dynamic Environments ◽  
Management Research ◽  
Data Set ◽  
Term Survival ◽  
Leadership And Management ◽  
Nationwide Study ◽  
Efficiency Control ◽  
Exploitation And Exploration ◽  
Discontinuous Innovation

Both organizational and management research suggest that schools and their leaders need to be ambidextrous to secure prosperity and long-term survival in dynamic environments characterized by competition and innovation. In this context, ambidexterity refers to the ability to simultaneously pursue exploitation and exploration and thus to deliver efficiency, control and incremental improvements while embracing flexibility, autonomy and discontinuous innovation. Using a unique, randomized and representative data set of N = 405 principals, we present findings on principals’ exploitation and exploration. The results indicate: (a) that principals engage far more often in exploitative than in explorative activities; (b) that exploitative activities in schools are executed at the expense of explorative activities; and (c) that explorative and ambidextrous activities of principals are positively associated with the (perceived) competition between schools. The study brings a novel perspective to educational research and demonstrates that applying the concept of ambidexterity has the potential to further our understanding of effective educational leadership and management.

Sign in / Sign up

Export Citation Format

Share Document