Gene copy number is associated with phytochemistry in Cannabis sativa

Abstract Gene copy number (CN) variation is known to be important in nearly every species where it has been examined. Alterations in gene CN may provide a fast way of acquiring diversity, allowing rapid adaptation under strong selective pressures, and may also be a key component of standing genetic variation within species. Cannabis sativa plants produce a distinguishing set of secondary metabolites, the cannabinoids, many of which have medicinal utility. Two major cannabinoids—THCA (delta-9-tetrahydrocannabinolic acid) and CBDA (cannabidiolic acid)—are products of a three-step biochemical pathway. Using whole-genome shotgun sequence data for 69 Cannabis cultivars from diverse lineages within the species, we found that genes encoding the synthases in this pathway vary in CN. Transcriptome sequence data show that the cannabinoid paralogs are differentially expressed among lineages within the species. We also found that CN partially explains variation in cannabinoid content levels among Cannabis plants. Our results demonstrate that biosynthetic genes found at multiple points in the pathway could be useful for breeding purposes, and suggest that natural and artificial selection have shaped CN variation. Truncations in specific paralogs are associated with lack of production of particular cannabinoids, showing how phytochemical diversity can evolve through a complex combination of processes.

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Gene copy number is associated with phytochemistry in Cannabis sativa

10.1101/736181 ◽

2019 ◽

Cited By ~ 1

Author(s):

Daniela Vergara ◽

Ezra L. Huscher ◽

Kyle G. Keepers ◽

Robert M. Givens ◽

Christian G. Cizek ◽

...

Keyword(s):

Copy Number ◽

Cannabis Sativa ◽

Gene Copy Number ◽

Gene Copy ◽

Biochemical Pathway ◽

Rapid Adaptation ◽

Selective Pressures ◽

Gene Copy Number Variation ◽

Genes Encoding ◽

Number Variation

AbstractGene copy number variation is known to be important in nearly every species where it has been examined. Alterations in gene copy number may provide a fast way of acquiring diversity, allowing rapid adaptation under strong selective pressures, and may also be a key component of standing genetic variation within species. Cannabis sativa plants produce a distinguishing set of secondary metabolites, the cannabinoids, many having medicinal utility. Two major cannabinoids -- THCA and CBDA -- are products of a three-step biochemical pathway. Using genomic data for 69 Cannabis cultivars from diverse lineages within the species, we found that genes encoding the synthases in this pathway vary in copy number, and that the cannabinoid paralogs may be differentially expressed. We also found that copy number partially explains variation in cannabinoid content levels among Cannabis plants.

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Investigations on Gene Copy Number, Introns and Chromosomal Arrangement of Genes Encoding the Fucoxanthin Chlorophyll a/c-Binding Proteins of the Centric Diatom Cyclotella cryptica

Protist ◽

10.1078/1434-4610-00005 ◽

2000 ◽

Vol 151 (1) ◽

pp. 27-39 ◽

Cited By ~ 18

Author(s):

Martin Eppard ◽

Erhard Rhiel

Keyword(s):

Chlorophyll A ◽

Copy Number ◽

Binding Proteins ◽

Gene Copy Number ◽

Gene Copy ◽

Centric Diatom ◽

Chromosomal Arrangement ◽

Genes Encoding ◽

Cyclotella Cryptica

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Assessment of HER-2/neu, с-MYC and CCNE1 gene copy number variations and protein expression in endometrial carcinomas

Experimental Oncology ◽

10.32471/exp-oncology.2312-8852.vol-41-no-2.12973 ◽

2019 ◽

Vol 41 (2) ◽

Author(s):

L.G. Buchynska ◽

◽

O.V. Brieieva* ◽

N.P. Iurchenko ◽

◽

...

Keyword(s):

Protein Expression ◽

Copy Number ◽

Gene Copy Number ◽

Copy Number Variations ◽

Gene Copy ◽

Her 2 ◽

Endometrial Carcinomas

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Faculty Opinions recommendation of Diet and the evolution of human amylase gene copy number variation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1092307.546722 ◽

2007 ◽

Author(s):

Magnus Ingelman-Sundberg

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Amylase Gene ◽

Gene Copy Number Variation ◽

Number Variation

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Faculty Opinions recommendation of RNA polymerase I activators count and adjust ribosomal RNA gene copy number.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734776122.793556076 ◽

2019 ◽

Author(s):

Angela Taddei

Keyword(s):

Rna Polymerase ◽

Ribosomal Rna ◽

Copy Number ◽

Gene Copy Number ◽

Rna Polymerase I ◽

Gene Copy ◽

Ribosomal Rna Gene ◽

Polymerase I

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Estimating Copy-Number Proportions: The Comeback of Sanger Sequencing

Genes ◽

10.3390/genes12020283 ◽

2021 ◽

Vol 12 (2) ◽

pp. 283

Author(s):

Eyal Seroussi

Keyword(s):

Copy Number ◽

Sanger Sequencing ◽

Cytosine Methylation ◽

Direct Sequencing ◽

Information Source ◽

Gene Copy Number ◽

Cost Effective ◽

Gene Copy ◽

Base Editing ◽

Recent Developments

Determination of the relative copy numbers of mixed molecular species in nucleic acid samples is often the objective of biological experiments, including Single-Nucleotide Polymorphism (SNP), indel and gene copy-number characterization, and quantification of CRISPR-Cas9 base editing, cytosine methylation, and RNA editing. Standard dye-terminator chromatograms are a widely accessible, cost-effective information source from which copy-number proportions can be inferred. However, the rate of incorporation of dye terminators is dependent on the dye type, the adjacent sequence string, and the secondary structure of the sequenced strand. These variable rates complicate inferences and have driven scientists to resort to complex and costly quantification methods. Because these complex methods introduce their own biases, researchers are rethinking whether rectifying distortions in sequencing trace files and using direct sequencing for quantification will enable comparable accurate assessment. Indeed, recent developments in software tools (e.g., TIDE, ICE, EditR, BEEP and BEAT) indicate that quantification based on direct Sanger sequencing is gaining in scientific acceptance. This commentary reviews the common obstacles in quantification and the latest insights and developments relevant to estimating copy-number proportions based on direct Sanger sequencing, concluding that bidirectional sequencing and sophisticated base calling are the keys to identifying and avoiding sequence distortions.

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Nongenotoxic ABCB1 activator tetraphenylphosphonium can contribute to doxorubicin resistance in MX-1 breast cancer cell line

Scientific Reports ◽

10.1038/s41598-021-86120-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Raimonda Kubiliute ◽

Indre Januskeviciene ◽

Ruta Urbanaviciute ◽

Kristina Daniunaite ◽

Monika Drobniene ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Protein Level ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Common Mechanism ◽

Dna Hypomethylation ◽

Mesenchymal Transition ◽

Molecular Features

AbstractHyperactivation of ABC transporter ABCB1 and induction of epithelial–mesenchymal transition (EMT) are the most common mechanism of acquired cancer chemoresistance. This study describes possible mechanisms, that might contribute to upregulation of ABCB1 and synergistically boost the acquisition of doxorubicin (DOX) resistance in breast cancer MX-1 cell line. DOX resistance in MX-1 cell line was induced by a stepwise increase of drug concentration or by pretreatment of cells with an ABCB1 transporter activator tetraphenylphosphonium (TPP+) followed by DOX exposure. Transcriptome analysis of derived cells was performed by human gene expression microarrays and by quantitative PCR. Genetic and epigenetic mechanisms of ABCB1 regulation were evaluated by pyrosequencing and gene copy number variation analysis. Gradual activation of canonical EMT transcription factors with later activation of ABCB1 at the transcript level was observed in DOX-only treated cells, while TPP+ exposure induced considerable activation of ABCB1 at both, mRNA and protein level. The changes in ABCB1 mRNA and protein level were related to the promoter DNA hypomethylation and the increase in gene copy number. ABCB1-active cells were highly resistant to DOX and showed morphological and molecular features of EMT. The study suggests that nongenotoxic ABCB1 inducer can possibly accelerate development of DOX resistance.

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