XJTU scientists publish research on opium poppy genome in Science

By Ian Graham and Li Guo Source:Xi’an Jiao Tong University Published: 2018/9/6 18:29:54

An international team of scientists, co-led by Kai Ye, professor at the School of Electronics and Information Engineering at Xi'an Jiao Tong University, and Ian Graham, professor at the University of York in the UK, and in partnership with Zemin Ning from Wellcome Trust Sanger Institute, have published the DNA sequence assembly of the opium poppy genome and uncovered key evolutionary steps in the production of the pharmaceutical compounds noscapine, codeine and morphine. The breakthrough, published in the latest issue of Science, reveals the origins of the pathway leading to production of the cough suppressant noscapine and the painkiller drugs codeine and morphine.

Photo: Courtesy of Xi'an Jiao Tong University

Throughout history opium poppy has been both a friend and foe to humanity. Morphinan-based painkillers are among the most effective and cheap treatment for the relief of severe pain and palliative care. Opium poppy also produces cough suppressant and anticancer noscapine. On the other hand, due to the addictive properties of morphinans, careful medical prescription is essential to avoid misuse. There is currently a huge discrepancy around the world in the dose of morphine equivalent available to alleviate serious health-related suffering with the USA and Canada having over 3,000 percent of estimated need being met, Western Europe 870 percent, China 16 percent, Russia 8 percent, India 4 percent and Nigeria 0.2 percent. Addressing the lack of access to pain relief or palliative care especially among poor people in low to middle income countries has recently been recognized as a global health and equity imperative. Decoding the genome of this important medicinal plant lays a foundation for exploiting its pharmaceutical potential through plant breeding and synthetic biology. 

Professor Kai Ye and his colleagues produced a high quality assembly of the 2.7 GigaBase opium poppy genome sequence distributed across 11 chromosomes. Plants have a remarkable capacity to duplicate their genomes and when this happens there is freedom for the duplicated genes to evolve to do other things. This has allowed plants to develop new machinery to make an amazingly diverse array of chemical compounds that are used to defend against attacks from harmful microbes and herbivores and to attract beneficial species, such as bees, to assist in pollination. Genome co-linearity analysis shows that opium poppy experienced a whole genome duplication (WGD) at around 7.8 million years ago and additional ancient duplication events at least 110 million years ago. 

Opium poppy genome features and evolutionary history. Photo: Courtesy of Xi'an Jiao Tong University

The genome assembly allowed the identification of 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. The genome assembly also allowed the identification of 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 - but was still long before our Homo sapien ancestors first emerged on planet Earth about 200,000 years ago. 

Compounds such as noscapine, codeine and morphine are chemically complex and chemical synthesis is difficult and much more expensive than plant based production. Synthetic biology based approaches are now being developed whereby genes from the plant are engineered into microbial systems such as yeast to enable production in industrial fermenters. However, opium poppy remains the cheapest and sole commercial source of these pharmaceutical compounds. The publication of the genome sequence will provide the foundation for further improvement of this medicinal plant for the pharmaceutical industry using molecular breeding approaches. 

Professor Kai Ye from Xi'an Jiaotong University said, "Highly repetitive plant genome and the intermingled evolutionary events in the past 100 million years complicate our analysis. 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."

Co-corresponding author, Professor Ian Graham, from the Centre for Novel Agricultural Products, Department of Biology at the University of York, said, "Biochemists have been curious for decades about how plants have evolved to become one of the richest sources of chemical diversity on earth. Using high quality genome assembly, our study has deciphered how this has happened in 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." 

Provided by

Ian Graham

Li Guo


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