A team of researchers from Australia, China and the United Kingdom has sequenced and analyzed the genome of the opium poppy (Papaver somniferum), a species of flowering plant in the family Papaveraceae. This breakthrough, reported in the journal Science, reveals the origins of the genetic pathway leading to the production of the cough suppressant noscapine and painkiller drugs morphine and codeine.
The poppy (Papaver somniferum). Image credit: Sabine Löwer.
“Biochemists have been curious for decades about how plants have evolved to become one of the richest sources of chemical diversity on Earth,” said co-lead author Professor Ian Graham, from the Centre for Novel Agricultural Products, Department of Biology at the University of York.
“Using high quality genome assembly, our study has deciphered how this has happened in the opium poppy.”
“At the same time this research 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,” he added.
Professor Graham and co-authors produced a high quality assembly of the 2.7-billion-base genome sequence distributed across 11 chromosomes.
This enabled the researchers to identify a large cluster of 15 genes that encode enzymes involved in two distinct biosynthetic pathways involved in the production of both noscapine and the compounds leading to codeine and morphine.
“Plants have the capacity to duplicate their genomes and when this happens there is freedom for the duplicated genes to evolve to do other things,” they explained.
“This has allowed plants to develop new machinery to make a diverse array of chemical compounds that are used to defend against attack from harmful microbes and herbivores and to attract beneficial species such as bees to assist in pollination.”
The poppy genome assembly allowed the team to identify the ancestral genes that came together to produce the STORR gene fusion that is responsible for the first major step on the pathway to morphine and codeine.
This fusion event happened before a relatively recent whole genome duplication event in the opium poppy genome 7.8 million years ago.
“Combining various sequencing technologies is the key for producing a high quality assembly for opium poppy genome,” said co-author Professor Zemin Ning, of the Wellcome Trust Sanger Institute.
“With a genome size similar to humans, the main challenge for this project was to handle repeat elements which make up 70.9% of the genome.”
“A highly repetitive plant genome and the intermingled evolutionary events in the past 100 million years complicated our analysis,” said co-lead author Professor Kai Ye, from the Xi’an Jiaotong University.
“We utilized complementary cutting-edge genome sequencing technologies with sophisticated mathematical models and analysis methods to investigate the evolutionary history of the opium poppy genome.”
“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.”
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Li Guo et al. The opium poppy genome and morphinan production. Science, published online August 30, 2018; doi: 10.1126/science.aat4096
