scholarly journals Dissecting the genetic basis of a complex cis-regulatory adaptation

2015 ◽  
Author(s):  
Santiago Naranjo ◽  
Justin Smith ◽  
Carlo Artieri ◽  
Mian Zhang ◽  
Yiqi Zhou ◽  
...  

Although single genes underlying several evolutionary adaptations have been identified, the genetic basis of complex, polygenic adaptations has been far more challenging to pinpoint. Here we report that the budding yeast Saccharomyces paradoxus has recently evolved resistance to citrinin, a naturally occurring mycotoxin. Applying a genome-wide test for selection on cis-regulation, we identified five genes involved in the citrinin response that are constitutively up-regulated in S. paradoxus. Four of these genes are necessary for resistance, and are also sufficient to increase the resistance of a sensitive strain when over-expressed. Moreover, cis-regulatory divergence in the promoters of these genes contributes to resistance, while exacting a cost in the absence of citrinin. Our results demonstrate how the subtle effects of individual regulatory elements can be combined, via natural selection, into a complex adaptation. Our approach can be applied to dissect the genetic basis of polygenic adaptations in a wide range of species.

Lab Animal ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 17-17
Author(s):  
Alexandra Le Bras

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1007
Author(s):  
Divya Kattupalli ◽  
Asha Sreenivasan ◽  
Eppurathu Vasudevan Soniya

Black pepper (Piper nigrum L.) is a prominent spice that is an indispensable ingredient in cuisine and traditional medicine. Phytophthora capsici, the causative agent of footrot disease, causes a drastic constraint in P. nigrum cultivation and productivity. To counterattack various biotic and abiotic stresses, plants employ a broad array of mechanisms that includes the accumulation of pathogenesis-related (PR) proteins. Through a genome-wide survey, eleven PR-1 genes that belong to a CAP superfamily protein with a caveolin-binding motif (CBM) and a CAP-derived peptide (CAPE) were identified from P. nigrum. Despite the critical functional domains, PnPR-1 homologs differ in their signal peptide motifs and core amino acid composition in the functional protein domains. The conserved motifs of PnPR-1 proteins were identified using MEME. Most of the PnPR-1 proteins were basic in nature. Secondary and 3D structure analyses of the PnPR-1 proteins were also predicted, which may be linked to a functional role in P. nigrum. The GO and KEGG functional annotations predicted their function in the defense responses of plant-pathogen interactions. Furthermore, a transcriptome-assisted FPKM analysis revealed PnPR-1 genes mapped to the P. nigrum-P. capsici interaction pathway. An altered expression pattern was detected for PnPR-1 transcripts among which a significant upregulation was noted for basic PnPR-1 genes such as CL10113.C1 and Unigene17664. The drastic variation in the transcript levels of CL10113.C1 was further validated through qRT-PCR and it showed a significant upregulation in infected leaf samples compared with the control. A subsequent analysis revealed the structural details, phylogenetic relationships, conserved sequence motifs and critical cis-regulatory elements of PnPR-1 genes. This is the first genome-wide study that identified the role of PR-1 genes during P. nigrum-P. capsici interactions. The detailed in silico experimental analysis revealed the vital role of PnPR-1 genes in regulating the first layer of defense towards a P. capsici infection in Panniyur-1 plants.


2012 ◽  
Vol 279 (1749) ◽  
pp. 5024-5028 ◽  
Author(s):  
Jacek Radwan ◽  
Wiesław Babik

The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far are beginning to challenge some widespread views of the way in which natural selection operates at the genomic level. Papers in this Special Feature of Proceedings of the Royal Society B illustrate various aspects of the broad field of adaptation genomics. This introductory article sets up a context and, on the basis of a few selected examples, discusses how genomic data can advance our understanding of the process of adaptation.


Genetics ◽  
2018 ◽  
Vol 210 (1) ◽  
pp. 203-218 ◽  
Author(s):  
Sultan Ciftci-Yilmaz ◽  
Wei-Chun Au ◽  
Prashant K. Mishra ◽  
Jessica R. Eisenstatt ◽  
Joy Chang ◽  
...  

2022 ◽  
Vol 12 ◽  
Author(s):  
Inge Holm ◽  
Luisa Nardini ◽  
Adrien Pain ◽  
Emmanuel Bischoff ◽  
Cameron E. Anderson ◽  
...  

Almost all regulation of gene expression in eukaryotic genomes is mediated by the action of distant non-coding transcriptional enhancers upon proximal gene promoters. Enhancer locations cannot be accurately predicted bioinformatically because of the absence of a defined sequence code, and thus functional assays are required for their direct detection. Here we used a massively parallel reporter assay, Self-Transcribing Active Regulatory Region sequencing (STARR-seq), to generate the first comprehensive genome-wide map of enhancers in Anopheles coluzzii, a major African malaria vector in the Gambiae species complex. The screen was carried out by transfecting reporter libraries created from the genomic DNA of 60 wild A. coluzzii from Burkina Faso into A. coluzzii 4a3A cells, in order to functionally query enhancer activity of the natural population within the homologous cellular context. We report a catalog of 3,288 active genomic enhancers that were significant across three biological replicates, 74% of them located in intergenic and intronic regions. The STARR-seq enhancer screen is chromatin-free and thus detects inherent activity of a comprehensive catalog of enhancers that may be restricted in vivo to specific cell types or developmental stages. Testing of a validation panel of enhancer candidates using manual luciferase assays confirmed enhancer function in 26 of 28 (93%) of the candidates over a wide dynamic range of activity from two to at least 16-fold activity above baseline. The enhancers occupy only 0.7% of the genome, and display distinct composition features. The enhancer compartment is significantly enriched for 15 transcription factor binding site signatures, and displays divergence for specific dinucleotide repeats, as compared to matched non-enhancer genomic controls. The genome-wide catalog of A. coluzzii enhancers is publicly available in a simple searchable graphic format. This enhancer catalogue will be valuable in linking genetic and phenotypic variation, in identifying regulatory elements that could be employed in vector manipulation, and in better targeting of chromosome editing to minimize extraneous regulation influences on the introduced sequences.Importance: Understanding the role of the non-coding regulatory genome in complex disease phenotypes is essential, but even in well-characterized model organisms, identification of regulatory regions within the vast non-coding genome remains a challenge. We used a large-scale assay to generate a genome wide map of transcriptional enhancers. Such a catalogue for the important malaria vector, Anopheles coluzzii, will be an important research tool as the role of non-coding regulatory variation in differential susceptibility to malaria infection is explored and as a public resource for research on this important insect vector of disease.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258657
Author(s):  
Abhirup Paul ◽  
Anurag P. Srivastava ◽  
Shreya Subrahmanya ◽  
Guoxin Shen ◽  
Neelam Mishra

Mitogen activated protein kinase kinase kinase (MAPKKK) form the upstream component of MAPK cascade. It is well characterized in several plants such as Arabidopsis and rice however the knowledge about MAPKKKs in tea plant is largely unknown. In the present study, MAPKKK genes of tea were obtained through a genome wide search using Arabidopsis thaliana as the reference genome. Among 59 candidate MAPKKK genes in tea, 17 genes were MEKK-like, 31 genes were Raf-like and 11 genes were ZIK- like. Additionally, phylogenetic relationships were established along with structural analysis, which includes gene structure, its location as well as conserved motifs, cis-acting regulatory elements and functional domain signatures that were systematically examined. Also, on the basis of one orthologous gene found between tea and Arabidopsis, functional interaction was carried out in C. sinensis based on an Arabidopsis association model. The expressional profiles indicated major involvement of MAPKKK genes from tea in response to various abiotic stress factors. Taken together, this study provides the targets for additional inclusive identification, functional study, and provides comprehensive knowledge for a better understanding of the MAPKKK cascade regulatory network in C. sinensis.


2020 ◽  
Author(s):  
SK Reilly ◽  
SJ Gosai ◽  
A Gutierrez ◽  
JC Ulirsch ◽  
M Kanai ◽  
...  

AbstractCRISPR screens for cis-regulatory elements (CREs) have shown unprecedented power to endogenously characterize the non-coding genome. To characterize CREs we developed HCR-FlowFISH (Hybridization Chain Reaction Fluorescent In-Situ Hybridization coupled with Flow Cytometry), which directly quantifies native transcripts within their endogenous loci following CRISPR perturbations of regulatory elements, eliminating the need for restrictive phenotypic assays such as growth or transcript-tagging. HCR-FlowFISH accurately quantifies gene expression across a wide range of transcript levels and cell types. We also developed CASA (CRISPR Activity Screen Analysis), a hierarchical Bayesian model to identify and quantify CRE activity. Using >270,000 perturbations, we identified CREs for GATA1, HDAC6, ERP29, LMO2, MEF2C, CD164, NMU, FEN1 and the FADS gene cluster. Our methods detect subtle gene expression changes and identify CREs regulating multiple genes, sometimes at different magnitudes and directions. We demonstrate the power of HCR-FlowFISH to parse genome-wide association signals by nominating causal variants and target genes.


2021 ◽  
Author(s):  
◽  
Noémie Valenza-Troubat

<p><b>Understanding the relationship between DNA sequence variation and the diversity of observable traits across the tree of life is a central research theme in biology. In all organisms, most traits vary continuously between individuals. Explaining the genetic basis of this quantitative variation requires disentangling genetic from non-genetic factors, as well as their interactions. The identification of causal genetic variants yields fundamental insights into how evolution creates diversity across the tree of life. Ultimately, this information can be used for medical, environmental and agricultural applications. Aquaculture is an industry that is experiencing significant global growth and is benefiting from the advances of genomic research. Genomic information helps to improve complex commercial phenotypes such as growth traits, which are easily quantified visually, but influenced by polygenes and multiple environmental factors, such as temperature. In the context of a global food crisis and environmental change, there is an urgent need not only to understand which genetic variants are potential candidates for selection gains, but also how the architecture of these traits are composed (e.g. monogenes, polygenes) and how they are influenced by and interact with the environment. The overall goal of this thesis research was to generate a genome-wide multi-omics dataset matched with exhaustive phenotypic information derived from a F0-F1 pedigree to investigate the quantitative genetic basis of growth in the New Zealand silver trevally (Pseudocaranx georgianus). These data were used to identify genomic regions that co-segregate with growth traits, and to describe the regulation of the genes involved in response to temperature fluctuations. The findings of this research helped gain fundamental insights into the genotype–phenotype map in an important teleost species and understand its ability to dynamically respond to temperature variations. This will ultimately support the establishment of a genomics-informed New Zealand aquaculture breeding programme. </b></p> <p>Chapter 1 of this thesis provides an overview of how genes interact with the environment to produce various growth phenotypes and how an understanding of this is important in aquaculture. This first chapter provides the deeper context for the research in subsequent data chapters. </p> <p>Chapter 2 describes the study population, the collection of phenotypic and genotypic data, and a first description of the genetic parameters of growth traits in trevally. A combination of Whole Genome Sequencing (WGS) and Genotyping-By-Sequencing (GBS) techniques were used to generate 60 thousand Single Nucleotide Polymorphism (SNP) markers for individuals in a two-generation pedigree. Together with phenotypic data, the genotyping data were used to reconstruct the pedigree, measure inbreeding levels, and estimate heritability for 10 growth traits. Parents were identified for 63% of the offspring and successful pedigree reconstruction indicated highly uneven contributions of each parent, and between the sexes, to the subsequent generation. The average inbreeding levels did not change between generations, but were significantly different between families. Growth patterns were found to be similar to that of other carangids and subject to seasonal variations. Heritability as well as genetic and phenotypic correlations were estimated using both a pedigree and a genomic relatedness matrix. All growth trait heritability estimates and correlations were found to be consistently high and positively correlated to each other. </p> <p>In Chapter 3, genotypic and phenotypic data were used to carry out linkage mapping and a genome-wide association study (GWAS) to map quantitative trait loci (QTLs) associated with growth differences in the F1 population. A linkage map was generated using the largest family, which allowed to scan for rare variants associated with the traits. The linkage map reported in this thesis is the first one for the Pseudocaranx genus and one of the densest for the carangid family. It included 19,861 SNPs contained in 24 linkage groups, which correspond to the 24 trevally chromosomes. Eight significant QTLs associated with height, length and weight were discovered on three linkage groups. Using GWAS, 113 SNPs associated with nine traits were identified and 29 genetic growth hot spots were uncovered. Two of the GWAS markers co-located with the QTLs discovered with the linkage mapping analysis. This demonstrates that combining QTL mapping and GWAS represents a powerful approach for the identification and validation of loci controlling complex phenotypes, such as growth, and provides important insights into the genetic architecture of these traits. </p> <p>Chapter 4, the last data chapter, investigates plasticity in gene expression patterns and growth of juvenile trevally, in response to different temperatures. Temperature conditions were experimentally manipulated for 1 month to mimic seasonal extremes. Phenotypic differences in growth were measured in 400 individuals, and the gene expression patterns of the pituitary gland and the liver were compared across treatments in a subset of 100 individuals, using RNA sequencing. Results showed that growth increased 50% more in the warmer compared with the colder condition, suggesting that temperature has a large impact on the metabolic activity associated with growth. We were able to annotate 27,887 gene models and found 39 differentially expressed genes (DEGs) in the pituitary, and 238 in the liver. Of these, 6 DEGs showed a common expression pattern between the tissues. Annotated blast matches of all DEGs revealed genes linked to major pathways affecting metabolism and reproduction. Our results indicate that native New Zealand trevally exhibit predictable plastic regulatory responses to temperature stress and the genes identified provide excellent for selective breeding objectives and studied how populations may adapt to increasing temperatures.</p> <p>Finally, Chapter 5 discusses the implications, future directions, and application of this research for trevally and other breeding programmes. It more broadly highlights the insights that were gained on the genetic architecture of growth, and the role of temperature in interacting and modulating genes involved in plastic growth responses.</p>


2018 ◽  
Vol 19 (1) ◽  
pp. 223-246 ◽  
Author(s):  
Saffron A.G. Willis-Owen ◽  
William O.C. Cookson ◽  
Miriam F. Moffatt

Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis—assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale—have substantially altered this landscape. Applications of such approaches are consistent with heterogeneity at the level of causation and specify patterns of commonality with a wide range of alternative disease traits. Looking beyond the individual as the unit of study, advances in technology have also fostered comprehensive analysis of the human microbiome and its varied roles in health and disease. In this article, we consider the implications of these technological advances for our current understanding of the genetics and genomics of asthma.


2018 ◽  
Vol 5 (1) ◽  
pp. 170925 ◽  
Author(s):  
Catherine R. M. Attard ◽  
Luciano B. Beheregaray ◽  
Jonathan Sandoval-Castillo ◽  
K. Curt S. Jenner ◽  
Peter C. Gill ◽  
...  

Genetic datasets of tens of markers have been superseded through next-generation sequencing technology with genome-wide datasets of thousands of markers. Genomic datasets improve our power to detect low population structure and identify adaptive divergence. The increased population-level knowledge can inform the conservation management of endangered species, such as the blue whale ( Balaenoptera musculus ). In Australia, there are two known feeding aggregations of the pygmy blue whale ( B. m. brevicauda ) which have shown no evidence of genetic structure based on a small dataset of 10 microsatellites and mtDNA. Here, we develop and implement a high-resolution dataset of 8294 genome-wide filtered single nucleotide polymorphisms, the first of its kind for blue whales. We use these data to assess whether the Australian feeding aggregations constitute one population and to test for the first time whether there is adaptive divergence between the feeding aggregations. We found no evidence of neutral population structure and negligible evidence of adaptive divergence. We propose that individuals likely travel widely between feeding areas and to breeding areas, which would require them to be adapted to a wide range of environmental conditions. This has important implications for their conservation as this blue whale population is likely vulnerable to a range of anthropogenic threats both off Australia and elsewhere.


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