scholarly journals Parallel and Population-specific Gene Regulatory Evolution in Cold-Adapted Fly Populations

Genetics ◽  
2021 ◽  
Author(s):  
Yuheng Huang ◽  
Justin B Lack ◽  
Grant T Hoppel ◽  
John E Pool
Keyword(s):  
Adaptive Evolution ◽  
Parallel Evolution ◽  
Natural Populations ◽  
Population Variation ◽  
Specific Gene ◽  
Regulatory Evolution ◽  
Cold Adapted ◽  
Thermal Environments ◽  
Gene Regulatory ◽  
Trans Regulation

Abstract Changes in gene regulation at multiple levels may comprise an important share of the molecular changes underlying adaptive evolution in nature. However, few studies have assayed within- and between-population variation in gene regulatory traits at a transcriptomic scale, and therefore inferences about the characteristics of adaptive regulatory changes have been elusive. Here, we assess quantitative trait differentiation in gene expression levels and alternative splicing (intron usage) between three closely-related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. The cold-adapted populations were known to show population genetic evidence for parallel evolution at the SNP level, and here we find evidence for parallel expression evolution between them, with stronger parallelism at larval and adult stages than for pupae. We also implement a flexible method to estimate cis- versus trans-encoded contributions to expression or splicing differences at the adult stage. The apparent contributions of cis- versus trans-regulation to adaptive evolution vary substantially among population pairs. While two of three population pairs show a greater enrichment of cis-regulatory differences among adaptation candidates, trans-regulatory differences are more likely to be implicated in parallel expression changes between population pairs. Genes with significant cis-effects are enriched for signals of elevated genetic differentiation between cold- and warm-adapted populations, suggesting that they are potential targets of local adaptation. These findings expand our knowledge of adaptive gene regulatory evolution and our ability to make inferences about this important and widespread process.

scholarly journals Evolution of Gene Expression and Splicing in Parallel Cold-Adapted Fly Populations

2019 ◽  
Author(s):  
Yuheng Huang ◽  
Justin B. Lack ◽  
Grant T. Hoppel ◽  
John E. Pool
Keyword(s):  
Gene Expression ◽  
Adaptive Evolution ◽  
Parallel Evolution ◽  
Population Variation ◽  
Regulatory Evolution ◽  
Cold Adapted ◽  
Mitochondrial Functions ◽  
Expression Evolution ◽  
Gene Regulatory ◽  
Trans Regulation

AbstractChanges in gene regulation at multiple levels may comprise an important share of the molecular changes underlying adaptive evolution in nature. However, few studies have assayed within- and between-population variation in gene regulatory traits at a transcriptomic scale, and therefore inferences about the characteristics of adaptive regulatory changes have been elusive. Here, we assess quantitative trait differentiation in gene expression levels and alternative splicing (intron usage) between three closely-related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. The cold-adapted populations were known to show population genetic evidence for parallel evolution at the SNP level, and here we find significant although somewhat limited evidence for parallel expression evolution between them, and less evidence for parallel splicing evolution. We find that genes with mitochondrial functions are particularly enriched among candidates for adaptive expression evolution. We also develop a method to estimate cis-versus trans-encoded contributions to expression or splicing differences that does not rely on the presence of fixed differences between parental strains. Applying this method, we infer important roles of both cis-and trans-regulation among our putatively adaptive expression and splicing differences. The apparent contributions of cis-versus trans-regulation to adaptive evolution vary substantially among population pairs, with an Ethiopian pair showing pervasive trans-effects, suggesting that basic characteristics of regulatory evolution may depend on biological context. These findings expand our knowledge of adaptive gene regulatory evolution and our ability to make inferences about this important and widespread process.

scholarly journals Gene regulatory evolution in cold-adapted fly populations neutralizes plasticity and may undermine genetic canalization

2022 ◽  
Author(s):  
Yuheng Huang ◽  
Justin Lack ◽  
Grant Hoppel ◽  
John E Pool
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Adaptive Evolution ◽  
Empirical Studies ◽  
Natural Populations ◽  
Plastic Response ◽  
Cold Adapted ◽  
Thermal Environments ◽  
Gene Regulatory ◽  
Transcriptomic Level

The relationships between adaptive evolution, phenotypic plasticity, and canalization remain incompletely understood. Theoretical and empirical studies have made conflicting arguments on whether adaptive evolution may enhance or oppose the plastic response. Gene regulatory traits offer excellent potential to study the relationship between plasticity and adaptation, and they can now be studied at the transcriptomic level. Here we take advantage of three closely-related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. We measure the transcriptome-wide plasticity in gene expression levels and alternative splicing (intron usage) between warm and cold laboratory environments. We find that suspected adaptive changes in both gene expression and alternative splicing tend to neutralize the ancestral plastic response. Further, we investigate the hypothesis that adaptive evolution can lead to decanalization of selected gene regulatory traits. We find strong evidence that suspected adaptive gene expression (but not splicing) changes in cold-adapted populations are more vulnerable to the genetic perturbation of inbreeding than putatively neutral changes. We find some evidence that these patterns may reflect a loss of genetic canalization accompanying adaptation, although other processes including hitchhiking recessive deleterious variants may contribute as well. Our findings augment our understanding of genetic and environmental effects on gene regulation in the context of adaptive evolution.

Adaptive NetworkProfiler for Identifying Cancer Characteristic-Specific Gene Regulatory Networks

2018 ◽  
Vol 25 (2) ◽  
pp. 130-145 ◽  
Author(s):  
Heewon Park ◽  
Teppei Shimamura ◽  
Seiya Imoto ◽  
Satoru Miyano
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Specific Gene ◽  
Gene Regulatory

Adaptive evolution of MRGX2, a human sensory neuron specific gene involved in nociception

Gene ◽  
2005 ◽  
Vol 352 ◽  
pp. 30-35 ◽  
Author(s):  
Su Yang ◽  
Ying Liu ◽  
Alice A. Lin ◽  
L. Luca Cavalli-Sforza ◽  
Zhongming Zhao ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Adaptive Evolution ◽  
Specific Gene

scholarly journals Deciphering the genetic links between NAFLD and co-occurring conditions using a liver gene regulatory network

2021 ◽  
Author(s):  
Sreemol Gokuladhas ◽  
William Schierding ◽  
Roan Eltigani Zaied ◽  
Tayaza Fadason ◽  
Murim Choi ◽  
...  
Keyword(s):  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Complex Traits ◽  
Target Genes ◽  
Specific Gene ◽  
Fat Percentage ◽  
Alcoholic Fatty Liver ◽  
Regulatory Interactions ◽  
Hepatic Diseases ◽  
Gene Regulatory

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a multi-system metabolic disease that co-occurs with various hepatic and extra-hepatic diseases. The phenotypic manifestation of NAFLD is primarily observed in the liver. Therefore, identifying liver-specific gene regulatory interactions between variants associated with NAFLD and multimorbid conditions may help to improve our understanding of underlying shared aetiology. Methods: Here, we constructed a liver-specific gene regulatory network (LGRN) consisting of genome-wide spatially constrained expression quantitative trait loci (eQTLs) and their target genes. The LGRN was used to identify regulatory interactions involving NAFLD-associated genetic modifiers and their inter-relationships to other complex traits. Results and Conclusions: We demonstrate that MBOAT7 and IL32, which are associated with NAFLD progression, are regulated by spatially constrained eQTLs that are enriched for an association with liver enzyme levels. MBOAT7 transcript levels are also linked to eQTLs associated with cirrhosis, and other traits that commonly co-occur with NAFLD. In addition, genes that encode interacting partners of NAFLD-candidate genes within the liver-specific protein-protein interaction network were affected by eQTLs enriched for phenotypes relevant to NAFLD (e.g. IgG glycosylation patterns, OSA). Furthermore, we identified distinct gene regulatory networks formed by the NAFLD-associated eQTLs in normal versus diseased liver, consistent with the context-specificity of the eQTLs effects. Interestingly, genes targeted by NAFLD-associated eQTLs within the LGRN were also affected by eQTLs associated with NAFLD-related traits (e.g. obesity and body fat percentage). Overall, the genetic links identified between these traits expand our understanding of shared regulatory mechanisms underlying NAFLD multimorbidities.

scholarly journals Cardiac Cell Type-Specific Gene Regulatory Programs and Disease Risk Association

2020 ◽  
Author(s):  
James D. Hocker ◽  
Olivier B. Poirion ◽  
Fugui Zhu ◽  
Justin Buchanan ◽  
Kai Zhang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cell Types ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Dependent Manner ◽  
Cardiac Cell ◽  
Risk Variants ◽  
Gene Regulatory

ABSTRACTBackgroundCis-regulatory elements such as enhancers and promoters are crucial for directing gene expression in the human heart. Dysregulation of these elements can result in many cardiovascular diseases that are major leading causes of morbidity and mortality worldwide. In addition, genetic variants associated with cardiovascular disease risk are enriched within cis-regulatory elements. However, the location and activity of these cis-regulatory elements in individual cardiac cell types remains to be fully defined.MethodsWe performed single nucleus ATAC-seq and single nucleus RNA-seq to define a comprehensive catalogue of candidate cis-regulatory elements (cCREs) and gene expression patterns for the distinct cell types comprising each chamber of four non-failing human hearts. We used this catalogue to computationally deconvolute dynamic enhancers in failing hearts and to assign cardiovascular disease risk variants to cCREs in individual cardiac cell types. Finally, we applied reporter assays, genome editing and electrophysiogical measurements in in vitro differentiated human cardiomyocytes to validate the molecular mechanisms of cardiovascular disease risk variants.ResultsWe defined >287,000 candidate cis-regulatory elements (cCREs) in human hearts at single-cell resolution, which notably revealed gene regulatory programs controlling specific cell types in a cardiac region/structure-dependent manner and during heart failure. We further report enrichment of cardiovascular disease risk variants in cCREs of distinct cardiac cell types, including a strong enrichment of atrial fibrillation variants in cardiomyocyte cCREs, and reveal 38 candidate causal atrial fibrillation variants localized to cardiomyocyte cCREs. Two such risk variants residing within a cardiomyocyte-specific cCRE at the KCNH2/HERG locus resulted in reduced enhancer activity compared to the non-risk allele. Finally, we found that deletion of the cCRE containing these variants decreased KCNH2 expression and prolonged action potential repolarization in an enhancer dosage-dependent manner.ConclusionsThis comprehensive atlas of human cardiac cCREs provides the foundation for not only illuminating cell type-specific gene regulatory programs controlling human hearts during health and disease, but also interpreting genetic risk loci for a wide spectrum of cardiovascular diseases.

scholarly journals What else is in an evolved name? Exploring evolvable specificity with SignalGP

2018 ◽  
Author(s):  
Alexander Lalejini ◽  
Charles Ofria
Keyword(s):  
Adaptive Evolution ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
De Novo ◽  
Direct Access ◽  
Evolutionary Transitions ◽  
Fine Grained ◽  
Flexible Mechanism ◽  
Gene Regulatory ◽  
Program Modules

Tags are evolvable labels that provide genetic programs a flexible mechanism for specification. Tags are used to label and refer to programmatic elements, such as functions or jump targets. However, tags differ from traditional, more rigid methods for handling labeling because they allow for inexact references; that is, a referring tag need not exactly match its referent. Here, we explore how adjusting the threshold for how what qualifies as a match affects adaptive evolution. Further, we propose broadened applications of tags in the context of a genetic programming (GP) technique called SignalGP. SignalGP gives evolution direct access to the event-driven paradigm. Program modules in SignalGP are tagged and can be triggered by signals (with matching tags) from the environment, from other agents, or due to internal regulation. Specifically, we propose to extend this tag based system to: (1) provide more fine-grained control over module execution and regulation (e.g., promotion and repression) akin to natural gene regulatory networks, (2) employ a mosaic of GP representations within a single program, and (3) facilitate major evolutionary transitions in individuality (i.e., allow hierarchical program organization to evolve de novo).

scholarly journals Inference of differential gene regulatory networks based on gene expression and genetic perturbation data

2019 ◽  
Vol 36 (1) ◽  
pp. 197-204 ◽  
Author(s):  
Xin Zhou ◽  
Xiaodong Cai
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Structural Equation ◽  
Regulatory Networks ◽  
Supplementary Information ◽  
Specific Gene ◽  
Joint Inference ◽  
Perturbation Data ◽  
Gene Regulatory ◽  
The Difference

Abstract Motivation Gene regulatory networks (GRNs) of the same organism can be different under different conditions, although the overall network structure may be similar. Understanding the difference in GRNs under different conditions is important to understand condition-specific gene regulation. When gene expression and other relevant data under two different conditions are available, they can be used by an existing network inference algorithm to estimate two GRNs separately, and then to identify the difference between the two GRNs. However, such an approach does not exploit the similarity in two GRNs, and may sacrifice inference accuracy. Results In this paper, we model GRNs with the structural equation model (SEM) that can integrate gene expression and genetic perturbation data, and develop an algorithm named fused sparse SEM (FSSEM), to jointly infer GRNs under two conditions, and then to identify difference of the two GRNs. Computer simulations demonstrate that the FSSEM algorithm outperforms the approaches that estimate two GRNs separately. Analysis of a dataset of lung cancer and another dataset of gastric cancer with FSSEM inferred differential GRNs in cancer versus normal tissues, whose genes with largest network degrees have been reported to be implicated in tumorigenesis. The FSSEM algorithm provides a valuable tool for joint inference of two GRNs and identification of the differential GRN under two conditions. Availability and implementation The R package fssemR implementing the FSSEM algorithm is available at https://github.com/Ivis4ml/fssemR.git. It is also available on CRAN. Supplementary information Supplementary data are available at Bioinformatics online.

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