The Origin of the World's Most Coveted Plant

The are few plants who have had such a major impact on human history as the opium poppy, papaver somniferium. It has been cultivated and grown for thousands of years and the plant was the catalyst for an entire war in the mid-1800s. Hundreds of thousands of people use the plant for its pain killing properties and some have succumbed to the it’s addictive nature. [1] Yet a good question to ask would be why does the opium poppy produce these painkilling chemicals? What purpose does it serve and how did this come to be? There are currently no bio-synthetic alternatives to the benzylisoquinoline alkaloids (BIAs) found in the poppy, so any further information on how they are produced could be beneficial. [2] A new journal article was recently published in Science Magazine that sheds light on this question and provides an evolutionary answer.

What the study found is that genome rearrangements have been critical in the evolution of the BIO metabolism in the opium poppy. There is a complex gene cluster that codes for many of the enzymes needed for the production for morphine and noscapine, and there is evidence that suggests that gene duplication, fusion, and rearrangement all led to the formation of this cluster. But what steps were necessary to deduce these results? They needed to sequence the genome.

The genome of papaver somniferium is very large and quite complex so a variety of strategies were incorporated to analyse the genome. The sequencing technologies of illumina paired-end and mate-pair, genomics linked reads, and pacific biosciences long read sequencing were used. [2] Oxford Nanopore and Illumina sequencing of bacterial artificial chromosomes were also used for quality checking. [2] The results of these sequencing methods can be seen displayed in the table 1 below.

Table 1 [2]

From the sequencing data the scientists were able to determine through the use of synteny analysis that a relatively recent genome wide duplication event had occurred. [2] Synteny analysis is basically the when one observes when the genes in different related species are both co-localized and then can use these observations to determine information about the species. [3] In this case the synteny analysis was done between P. somniferium and a variety of other species, the results of which can be seen in figure 1. The figure shows a major whole genome duplication peak and a minor segmental duplication peak, which indicates that at some point there was a genome wide duplication event. [2]

Figure 1 [2]

But when did this whole-genome duplication event happen? Was it recent or did it happen to some ancestral species of plant that wasn’t P. somniferium? To find this the scientists used OrthoFinder and BEAST to analyse 48 orthologs across 11 closely related angiosperm species. [2] This analysis allowed them to create a phylogeny which mapped when each of the angiosperm species diverged and where the whole-genome duplication event likely happened. This generated phylogeny can be seen in figure 2 and shows that the whole-genome duplication event was an estimated 7.8 million years ago which is after P. somniferium diverged from the other species.

Figure 2. [2]

But which part of the P. somniferium genome is responsible for the BIA production? This was found by simply looking at the genome analysis that was previously done and they were able to find all of the genes which were associated with BIA production. From this they found that the noscapine gene cluster, the genes responsible for the production of the morphinan alkaloid thebaine, and the (S) to (R)-reticuline (STORR) gene fusion were all in the same region on chromosome 11. [2] This region is referred to as the BIA gene cluster. Notably, this gene cluster does not contain any of the other genes associated with BIA production and none of these other genes are in other clusters. [2] The mechanism of BIA production can be seen in figure 3, the ones that are highlighted green can be found in the BIA cluster.

Figure 3 [2]

Now that we have identified the BIA cluster, what is its evolutionary history? To answer this question the scientists used MCScanX to perform synteny analysis to find places with close homology to the BIA cluster. [2] This analysis revealed that the top ranked blocks for the noscapine branch genes only had distant homology but the top ranked blocks for the morphinan pathway had close homology and was on unplaced scaffold 21. [2] They then found that the morphinan pathway gene syntenic block is due to a duplication occuring at the same time as the whole-genome duplication event. [2] This was found through Ks and amino acid identity of syntenic gene pairs. [2]

Gene family analysis on the STORR part of the BIA cluster revealed even more interesting information. They found that the closest paralogs for the two parts of the STORR were on chromosome 2, separated by 865-bp. [2] What does this separation indicate? Most likely this means that the STORR gene was formed through the fusion of the two parts. How could this happen? The most probable explanation is that the gene was duplicated and then there was a deletion event which deleted the 865-bp which separate the two parts of the gene.

When did the BIA gene cluster form? Through more phylogenetic analysis it was revealed that STORR and the other parts of the BIA cluster emerged before the whole-genome duplication. [2] Thus the likely order of events is that the BIA cluster was assembled and then the whole-genome duplication event occured, once this happened the two parts of the STORR were fused together through some form of deletion. Still this begs the question as to why the BIA gene cluster formed. The most plausible explanation is that there was a strong selection pressure which favored the genes involved in the process of BIA production clustering together.

Why aren’t the other genes involved in BIA production also part of the cluster? In the case of the genes which code for berberine bridge enzyme (BBE) and tetrahydroprotoberberine N-methyltransferase (TNMT), proteins involved in the biosynthesis of noscapine, there is an answer. [2] BBE and TNMT are also used for sanguinarine biosynthesis and are not only used for noscapine biosynthesis. [2] This pathway can be seen in figure 4. Sanguinarine is use predominantly in root tissues whilst noscapine biosynthesis is used in root tissues. [2] It is possible that there were selection pressures on the genes coding for BBE and TNMT to not be part of the gene cluster due to their use in the sanguinarine pathway in other parts of the plant.

Figure 4 [4]

In conclusion, this recent study revealed that genome rearrangements have been important in the evolution of BIA metabolism in the opium poppy. Many factors were at play in the formation of this metabolism and the data indicates that there was at least one recent whole-genome duplication event in the opium poppy’s history.


  1. “Cannabis, Coca, & Poppy: Nature’s Addictive Plants.” DEA Museum. N.p., n.d. Web.
  2. Guo, Li, Thilo Winzer, Xiaofei Yang, Yi Li, Zemin Ning, Roxana Teodor, Ying Lu, Tim A. Bowser, Ian A. Graham, and Kai Ye. “The Opium Poppy Genome and Morphinan Production.” Science. American Association for the Advancement of Science, 19 Oct. 2018. Web.
  3. Liu, Dang, Martin Hunt, and Isheng J. Tsai. “Inferring Synteny between Genome Assemblies: A Systematic Evaluation.” BMC Bioinformatics. BioMed Central, 30 Jan. 2018. Web.
  4. Desgagné-Penix, Isabel, Morgan F Khan, David C Schriemer, Dustin Cram, Jacek Nowak, and Peter J Facchini. “Integration of Deep Transcriptome and Proteome Analyses Reveals the Components of Alkaloid Metabolism in Opium Poppy Cell Cultures.” BMC Plant Biology. BioMed Central, 18 Nov. 2010. Web.