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Opium Poppy Genome Provides Look at Painkiller Compound Evolution

NEW YORK (GenomeWeb) – A new draft genome sequence for the opium poppy, Papaver somniferum, is helping scientists dig into the evolution of pathways producing morphine, codeine, and noscapine (a cough suppressant) — findings that have potential implications for the plant breeding and pharmaceutical communities.

Ian Graham, with the University of York's Centre for Novel Agricultural Products, said in a statement that the results "will provide the foundation for the development of molecular plant breeding tools that can be used to ensure there is a reliable and cheap supply of the most effective painkillers available for pain relief and palliative care for societies in not just developed but also developing world countries."

Graham and colleagues from the UK, China, and Australia sequenced and assembled a 2.72-billion-base draft genome assembly for the opium poppy using a combination of Illumina, 10X Genomics, Pacific Biosciences, and Oxford Nanopore technologies — work they reported online yesterday in Science. Together with RNA sequence data from seven poppy tissues, the genome led them to more than 51,200 predicted protein-coding genes, nearly 9,500 non-coding RNAs, and rampant repetitive element sequences scattered across 11 chromosomes.

And through a series of syntenic, phylogenetic, and functional analyses of the opium poppy, the team detected duplication events that took place an estimated 7.8 million years ago and 110 million years ago. In conjunction with subsequent rearrangement and fusion events, such duplications helped to produce a single benzylisoquinoline alkaloid (BIA) gene cluster on chromosome 11 that contains 15 enzyme-coding genes involved in phthalideisoquinoline and morphinan biosynthesis.

The morphinan pathway leads to well-known painkillers such as morphine and codeine, the team explained, while phthalideisoquinoline genes produce noscapine, a compound with cough suppression and anti-cancer properties.

"It is intriguing that two biosynthetic pathways came to the same genomic region due to a series of duplication, shuffling, and fusion structural events, enabling concerted production of novel metabolic compounds," co-corresponding author Kai Ye, a researcher affiliated with Xi'an Jiaotong University and Fudan University, said in a statement.

With the analyses enabled by the new opium poppy genome assembly, the investigators saw that sets of genes that seem to have exclusive functions in the morphinan or phthalideisoquinoline biosynthetic pathways belong to the BIA cluster. But for biosynthetic genes showing additional functions in the plant, that was not always the case.

"The presence of genes exclusively associated with biosynthesis of both phthalideisoquinolines and morphinans in the BIA gene cluster implies a selection pressure favoring clustering of genes associated with these classes of alkaloids," Ye and his co-authors wrote, noting that selection may have kept other noscapine genes with roles beyond this pathway from falling in the same cluster.

"Coordinate regulation of gene expression is considered to be part of the selective pressure resulting in gene cluster formation," they concluded. "In opium poppy, the exclusivity of gene function and complexity of the gene expression patterns, could have determined which genes are clustered."

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