Search bioRxiv⌕ Search

bioRxiv · 10.1101/2025.04.03.647041

Uncovering the molecular basis of high morphinan product efficiency in opium poppy through Multi-omics integrated analysis with multi-capsules

Abstract

Exploring the genetic landscape and corresponding regulatory mechanisms influencing morphine and related alkaloid production efficiency in the opium poppy (Papaver Somniferum L.) is important for sustainable medicinal production. However, information regarding the corresponding medicinal properties of poppy subspecies remains elusive, and the correlation between agronomic traits and morphine production remains unclear. Therefore, this study aims to investigate the distinction between two poppy subspecies: Shan Yang (SY) and Lan Tian (LT). Physiological data revealed that SY exhibited greater tolerance to environmental stress and a higher morphine content than LT, especially during the reproductive stage. To investigate genetic and molecular mechanisms underlying different tolerance traits and morphine synthesis efficiencies, a comprehensive comparison of genomic, transcriptomic, and metabolomic data was conducted, showing significantly higher single nucleotide polymorphism (SNP) frequency in SY (23.78%) compared to LT (23.69%). The proportions of SKIP (Skipped Exon) and MIR (Multi Intron Retention) were higher in SY than in LT. SY showed significantly higher gene expression related to benzylisoquinoline alkaloid synthesis, especially those involved in the steps from 1,2 dehydroreticulinium to morphine, narcotoline and noscapine, compared to LT. The upregulated expression of phenylpropanoid biosynthesis-related genes contributes to its more resistant agronomical traits. It plays a synergistic role in alkaloid production. The higher morphine content in SY resulted from an integrated effect controlled at different levels. Summarily, our findings offer new insights into the molecular mechanisms of morphine synthesis and present valuable gene resources for improving poppy cultivars with higher morphine content.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Huang, Y., Sun, M., Gong, W., Liu, Y., Cheng, Y., Yuan, L., Wu, Y.. 2025-04-08. Uncovering the molecular basis of high morphinan product efficiency in opium poppy through Multi-omics integrated analysis with multi-capsules. https://doi.org/10.1101/2025.04.03.647041

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Structural variation in repeat elements is widespread in normal human tissues and in tumorigenesis

Somatic mosaicism contributes to genomic variation, yet postzygotic structural variants remain under-characterized. We performed long- and short-read WGS from multiple individuals (n=47 normal tissues; n=168 samples) and identified mosaic structural variants in all individuals and germ layers, impacting a median 285.2 kb/genome. Nearly half of breakpoints were independently validated, with tissue distributions reflecting both early and late developmental origins. Most mosaic variants were repeat-mediated and 8.3% overlapped functional elements, an enrichment compared to germline variants. To extend these analyses in samples where long-read sequencing is infeasible, we measured repeat alterations from short-read sequencing, recapitulating mosaic tissue-specific differences. We characterized tumor- and tissue- specific variation in repeats across 15 cancer types and found tumor-related repeat variation to be similar in scale to that of normal mosaic variation. Tracking repeat changes in cell-free DNA provided a noninvasive approach for tumor monitoring. Our analyses revealed widespread repeat-driven structural variation in health and disease.

genomics↗

RNA isoform-resolved multiplexed sequencing with bioorthogonal barcoding

RNA isoform dysregulation drives disease pathogenesis and is the target of FDA-approved splice-switching therapeutics. However, multiplexed sequencing methods discard splice junction information because only 3' termini are barcoded and counted. Here, we repurpose acylation and click chemistries to conjugate bioorthogonal barcodes (bobcodes) directly onto multiple internal positions along cellular RNAs. Bobcoded RNAs from multiple samples are pooled for multiplexed cDNA synthesis, during which reverse transcriptase switches from each RNA template onto its tethered bobcode with greater than 99% accuracy in species mixing experiments. Bobcode attachment intervals set cDNA insert sizes without a library fragmentation step, and priming with poly(dT) or random hexamers selects between 3'-end counting and full-length isoform capture. A bioorthogonal barcode-sequencing (BOB-seq v0.1) drug screen identifies transcriptome-wide on- and off-target RNA splicing effects and outperforms existing multiplexing RNA sequencing methods in workflow simplicity, sample-to-sample variability, and barcoding accuracy. Bobcodes add isoform resolution to scalable multiplexed RNA sequencing.

genomics↗

Structural polymorphism and population-variable coding capacity of HERV-K(HML-2) in human pangenomes

Approximately 8% of the human genome is derived from ancient retroviral infections. The most recently integrated of these endogenous retroviruses is the HERV-K(HML-2) clade, whose expression has been associated with cancer, amyotrophic lateral sclerosis, and embryogenesis. Studies of HERV expression, particularly HML-2, have relied predominantly on short-read sequencing. However, the high similarity among HML-2 proviruses prevents many short reads from being assigned uniquely to individual loci. We therefore compared haplotype-resolved long-read genome assemblies from 292 donors to resolve variation in proviral structure and coding capacity. Several loci previously thought to be fixed were structurally polymorphic. Tandem arrays occurred at 13 loci and contained up to six proviral copies in a single array. At 8q11.23, we identified a previously undescribed full-length provirus in one haplotype. All 583 other haplotypes carried a solo-LTR. We found that standard reference genomes failed to represent the coding capacity retained in many individuals, whose proviruses contained intact open reading frames despite disruptive mutations in the reference sequences. Short-read genotypes left 32.5% of the tested donor-variant pairs unresolved at sites associated with viral reading frames. These findings show why HML-2 expression must be interpreted in the context of the structural and coding alleles each individual carries.

genomics↗