Travel Tales of a Worldwide Weed: Genomic Signatures of Plantago major L. Reveal Distinct Genotypic Groups With Links to Colonial Trade Routes.

Retracing pathways of historical species introductions is fundamental to understanding the factors involved in the successful colonization and spread, centuries after a species' establishment in an introduced range. Numerous plants have been introduced to regions outside their native ranges both intentionally and accidentally by European voyagers and early colonists making transoceanic journeys; however, records are scarce to document this. We use genotyping-by-sequencing and genotype-likelihood methods on the selfing, global weed, Plantago major, collected from 50 populations worldwide to investigate how patterns of genomic diversity are distributed among populations of this global weed. Although genomic differentiation among populations is found to be low, we identify six unique genotype groups showing very little sign of admixture and low degree of outcrossing among them. We show that genotype groups are latitudinally restricted, and that more than one successful genotype colonized and spread into the introduced ranges. With the exception of New Zealand, only one genotype group is present in the Southern Hemisphere. Three of the most prevalent genotypes present in the native Eurasian range gave rise to introduced populations in the Americas, Africa, Australia, and New Zealand, which could lend support to the hypothesis that P. major was unknowlingly dispersed by early European colonists. Dispersal of multiple successful genotypes is a likely reason for success. Genomic signatures and phylogeographic methods can provide new perspectives on the drivers behind the historic introductions and the successful colonization of introduced species, contributing to our understanding of the role of genomic variation for successful establishment of introduced taxa.

Assessing Specialized Metabolite Diversity in the Cosmopolitan Plant Genus Euphorbia L.

Coevolutionary theory suggests that an arms race between plants and herbivores yields increased plant specialized metabolite diversity and the geographic mosaic theory of coevolution predicts that coevolutionary interactions vary across geographic scales. Consequently, plant specialized metabolite diversity is expected to be highest in coevolutionary hotspots, geographic regions, which exhibit strong reciprocal selection on the interacting species. Despite being well-established theoretical frameworks, technical limitations have precluded rigorous hypothesis testing. Here we aim at understanding how geographic separation over evolutionary time may have impacted chemical differentiation in the cosmopolitan plant genus Euphorbia. We use a combination of state-of-the-art computational mass spectral metabolomics tools together with cell-based high-throughput immunomodulatory testing. Our results show significant differences in specialized metabolite diversity across geographically separated phylogenetic clades. Chemical structural diversity of the highly toxic Euphorbia diterpenoids is significantly reduced in species native to the Americas, compared to Afro-Eurasia. The localization of these compounds to young stems and roots suggest a possible ecological relevance in herbivory defense. This is further supported by reduced immunomodulatory activity in the American subclade as well as herbivore distribution patterns. We conclude that computational mass spectrometric metabolomics coupled with relevant ecological data provide a strong tool for exploring plant specialized metabolite diversity in a chemo-evolutionary framework.

A phylogenetic road map to antimalarial Artemisia species.

ETHNOPHARMACOLOGICAL RELEVANCE: The discovery of the antimalarial agent artemisinin is considered one of the most significant success stories of ethnopharmacological research in recent times. The isolation of artemisinin was inspired by the use of Artemisia annua in traditional Chinese medicine (TCM) and was awarded a Nobel Prize in 2015. Antimalarial activity has since been demonstrated for a range of other Artemisia species, suggesting that the genus could provide alternative sources of antimalarial treatments. Given the stunning diversity of the genus (c. 500 species), a prioritisation of taxa to be investigated for their likely antimalarial properties is required. MATERIALS AND METHODS: Here we use a phylogenetic approach to explore the potential for identifying species more likely to possess antimalarial properties. Ethnobotanical data from literature reports is recorded for 117 species. Subsequent phylogenetically informed analysis was used to identify lineages in which there is an overrepresentation of species used to treat malarial symptoms, and which could therefore be high priority for further investigation of antimalarial activity. RESULTS: We show that these lineages indeed include several species with documented antimalarial activity. To further inform our approach, we use LC-MS/MS analysis to explore artemisinin content in fifteen species from both highlighted and not highlighted lineages. We detected artemisinin in nine species, in eight of them for the first time, doubling the number of Artemisia taxa known to content this molecule. CONCLUSIONS: Our findings indicate that artemisinin may be widespread across the genus, providing an accessible local resource outside the distribution area of Artemisia annua.

Fundamental species traits explain provisioning services of tropical American palms.

The well-being of the global human population rests on provisioning services delivered by 12% of the Earth's ∼400,000 plant species1. Plant utilization by humans is influenced by species traits2-4, but it is not well understood which traits underpin different human needs5. Here, we focus on palms (Arecaceae), one of the most economically important plant groups globally6, and demonstrate that provisioning services related to basic needs, such as food and medicine, show a strong link to fundamental functional and geographic traits. We integrate data from 2,201 interviews on plant utilization from three biomes in South America-spanning 68 communities, 43 ethnic groups and 2,221 plant uses-with a dataset of 4 traits (leaf length, stem volume, fruit volume, geographic range size) and a species-level phylogeny7. For all 208 palm species occurring in our study area, we test for relations between their traits and perceived value. We find that people preferentially use large, widespread species rather than small, narrow-ranged species, and that different traits are linked to different uses. Further, plant size and geographic range size are stronger predictors of ecosystem service realization for palm services related to basic human needs than less-basic needs (for example, ritual). These findings suggest that reliance on plant size and availability may have prevented our optimal realization of wild-plant services, since ecologically rare yet functionally important (for example, chemically) clades may have been overlooked. Beyond expanding our understanding of how local people use biodiversity in mega-diverse regions, our trait- and phylogeny-based approach helps to understand the processes that underpin ecosystem service realization, a necessary step to meet societal needs in a changing world with a growing human population5,8.

Evolutionary prediction of medicinal properties in the genus Euphorbia L.

The current decrease of new drugs brought to the market has fostered renewed interest in plant-based drug discovery. Given the alarming rate of biodiversity loss, systematic methodologies in finding new plant-derived drugs are urgently needed. Medicinal uses of plants were proposed as proxy for bioactivity, and phylogenetic patterns in medicinal plant uses have suggested that phylogeny can be used as predictive tool. However, the common practice of grouping medicinal plant uses into standardised categories may restrict the relevance of phylogenetic predictions. Standardised categories are mostly associated to systems of the human body and only poorly reflect biological responses to the treatment. Here we show that medicinal plant uses interpreted from a perspective of a biological response can reveal different phylogenetic patterns of presumed underlying bioactivity compared to standardised methods of medicinal plant use classification. In the cosmopolitan and pharmaceutically highly relevant genus Euphorbia L., identifying plant uses modulating the inflammatory response highlighted a greater phylogenetic diversity and number of potentially promising species than standardised categories. Our interpretation of medicinal plant uses may therefore allow for a more targeted approach for future phylogeny-guided drug discovery at an early screening stage, which will likely result in higher discovery rates of novel chemistry with functional biological activity.

Global medicinal uses of Euphorbia L. (Euphorbiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Euphorbia (spurges, Euphorbiaceae) is the third largest genus of flowering plants, with almost 2000 species. Its exceptional diversity of growth forms and near-cosmopolitan distribution have attracted human interest since ancient times. For instance in Australia, topical application of latex of Euphorbia peplus L. is used as a home treatment for skin cancer and actinic keratosis. Its use in Australian folk medicine has inspired the release of the drug Picato® (ingenol mebutate), and further fostered interest in natural products and medicinal uses of Euphorbia in recent years. AIM OF THE STUDY: To provide an indicative overview of medicinal uses of the genus Euphorbia driven by the recent interest in biologically active natural products from Euphorbia in drug discovery. We assess documented medicinal knowledge and value of the genus Euphorbia and the taxonomic distribution of this value. MATERIALS AND METHODS: We undertook an extensive survey of over 260 multidisciplinary publications on the online repository JSTOR using the search term "Euphorbia medicinal". RESULTS: Medicinal uses were identified for >5% of the species in the genus, including descriptions of treatments for a variety of diseases. The most-cited medicinal uses around the world were treatments for digestive system disorders, skin ailments and, especially in the Southern hemisphere, infections. Consensus ratios indicated that the most-valued medicinal uses of Euphorbia species are in the treatment of digestive and respiratory complaints, inflammation and injuries, especially by members of Euphorbia subg. Chamaesyce. CONCLUSIONS: The present study gives a first indicative overview of Euphorbia species used for health and wellbeing around the world. The exceptional diversity of the genus Euphorbia is not only represented by its growth forms but also by its diverse medicinal uses. Our results highlight the importance of research into medicinal uses of Euphorbia species and their importance as a source of natural products. Furthermore the medicinally highly valuable subgenus Chamaesyce was identified as chemically under-investigated, emphasizing the need for further studies investigating the chemical diversity to which the high medicinal value of Euphorbia subg. Chamaesyce can be attributed.

Identification of common horsetail (Equisetum arvense L.; Equisetaceae) using Thin Layer Chromatography versus DNA barcoding.

The global herbal products market has grown in recent years, making regulation of these products paramount for public healthcare. For instance, the common horsetail (Equisetum arvense L.) is used in numerous herbal products, but it can be adulterated with closely related species, especially E. palustre L. that can produce toxic alkaloids. As morphology-based identification is often difficult or impossible, the identification of processed material can be aided by molecular techniques. In this study, we explore two molecular identification techniques as methods of testing the purity of these products: a Thin Layer Chromatography approach (TLC-test) included in the European Pharmacopoeia and a DNA barcoding approach, used in recent years to identify material in herbal products. We test the potential of these methods for distinguishing and identifying these species using material from herbarium collections and commercial herbal products. We find that both methods can discriminate between the two species and positively identify E. arvense. The TLC-test is more cost- and time-efficient, but DNA barcoding is more powerful in determining the identity of adulterant species. Our study shows that, although DNA barcoding presents certain advantages, other established laboratory methods can perform as well or even better in confirming species' identity in herbal products.

Predicting species' tolerance to salinity and alkalinity using distribution data and geochemical modelling: a case study using Australian grasses.

BACKGROUND AND AIMS: Salt tolerance has evolved many times independently in different plant groups. One possible explanation for this pattern is that it builds upon a general suite of stress-tolerance traits. If this is the case, then we might expect a correlation between salt tolerance and other tolerances to different environmental stresses. This association has been hypothesized for salt and alkalinity tolerance. However, a major limitation in investigating large-scale patterns of these tolerances is that lists of known tolerant species are incomplete. This study explores whether species' salt and alkalinity tolerance can be predicted using geochemical modelling for Australian grasses. The correlation between taxa found in conditions of high predicted salinity and alkalinity is then assessed. METHODS: Extensive occurrence data for Australian grasses is used together with geochemical modelling to predict values of pH and electrical conductivity to which species are exposed in their natural distributions. Using parametric and phylogeny-corrected tests, the geochemical predictions are evaluated using a list of known halophytes as a control, and it is determined whether taxa that occur in conditions of high predicted salinity are also found in conditions of high predicted alkalinity. KEY RESULTS: It is shown that genera containing known halophytes have higher predicted salinity conditions than those not containing known halophytes. Additionally, taxa occurring in high predicted salinity tend to also occur in high predicted alkalinity. CONCLUSIONS: Geochemical modelling using species' occurrence data is a potentially useful approach to predict species' relative natural tolerance to challenging environmental conditions. The findings also demonstrate a correlation between salinity tolerance and alkalinity tolerance. Further investigations can consider the phylogenetic distribution of specific traits involved in these ecophysiological strategies, ideally by incorporating more complete, finer-scale geochemical information, as well as laboratory experiments.

The evolution of traditional knowledge: environment shapes medicinal plant use in Nepal.

Traditional knowledge is influenced by ancestry, inter-cultural diffusion and interaction with the natural environment. It is problematic to assess the contributions of these influences independently because closely related ethnic groups may also be geographically close, exposed to similar environments and able to exchange knowledge readily. Medicinal plant use is one of the most important components of traditional knowledge, since plants provide healthcare for up to 80% of the world's population. Here, we assess the significance of ancestry, geographical proximity of cultures and the environment in determining medicinal plant use for 12 ethnic groups in Nepal. Incorporating phylogenetic information to account for plant evolutionary relatedness, we calculate pairwise distances that describe differences in the ethnic groups' medicinal floras and floristic environments. We also determine linguistic relatedness and geographical separation for all pairs of ethnic groups. We show that medicinal uses are most similar when cultures are found in similar floristic environments. The correlation between medicinal flora and floristic environment was positive and strongly significant, in contrast to the effects of shared ancestry and geographical proximity. These findings demonstrate the importance of adaptation to local environments, even at small spatial scale, in shaping traditional knowledge during human cultural evolution.

Phylogenies reveal predictive power of traditional medicine in bioprospecting.

There is controversy about whether traditional medicine can guide drug discovery, and investment in bioprospecting informed by ethnobotanical data has fluctuated. One view is that traditionally used medicinal plants are not necessarily efficacious and there are no robust methods for distinguishing those which are most likely to be bioactive when selecting species for further testing. Here, we reconstruct a genus-level molecular phylogenetic tree representing the 20,000 species found in the floras of three disparate biodiversity hotspots: Nepal, New Zealand, and the Cape of South Africa. Borrowing phylogenetic methods from community ecology, we reveal significant clustering of the 1,500 traditionally used species, and provide a direct measure of the relatedness of the three medicinal floras. We demonstrate shared phylogenetic patterns across the floras: related plants from these regions are used to treat medical conditions in the same therapeutic areas. This finding strongly indicates independent discovery of plant efficacy, an interpretation corroborated by the presence of a significantly greater proportion of known bioactive species in these plant groups than in random samples. We conclude that phylogenetic cross-cultural comparisons can focus screening efforts on a subset of traditionally used plants that are richer in bioactive compounds, and could revitalize the use of traditional knowledge in bioprospecting.

Cross-cultural comparison of medicinal floras used against snakebites.

ETHNOPHARMACOLOGICAL RELEVANCE: Envenomation causes an estimated 1.8-2.5 million incidences per year with a mortality level of 100-125,000 persons annually and more than 100,000 individuals suffer from severe complications, which may end in amputation of the attacked limb. The use of plants is a major part of the traditional practitioners' treatment of snakebites. MATERIALS AND METHODS: A database was created for plants used to treat snakebites worldwide. From this database, we selected five countries with a high number of entries and representing different cultures, geography and floristic zones: Brazil, Nicaragua, Nepal, China and South Africa. The datasets were analysed by regression and binominal analysis to see if any family or genus used against snakebites was overrepresented in the respective traditional medicinal systems relative to the abundance in the local flora. The families from the different geographical areas were compared to ascertain whether the same plant families are preferred by different peoples. RESULTS: Three 'hot' families (Apocynaceae, Lamiaceae and Rubiaceae) were recovered in at least two of the five compared countries in the regression analyses and one 'hot' family (Zingiberaceae) was recovered in two of the compared countries in the binomial analyses. Four out of five floras possess families identified as outliers in both regression and binomial analyses. Eight families were recovered by both the binomial and the regression analysis (40-62% of all highlighted families respectively). At the genus level, only Piper (Piperaceae) was recovered as a 'hot' genus in at least two floras. Seven genera were highlighted by both analyses (25-44% of the highlighted genera). CONCLUSIONS: Cross-cultural comparison of medicinal floras used against snakebites appears to be useful for highlighting candidate families and genera for further studies.

The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae).

BACKGROUND: The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships. CONCLUSIONS/SIGNIFICANCE: This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds.

Cross-cultural comparison of three medicinal floras and implications for bioprospecting strategies.

ETHNOPHARMACOLOGICAL RELEVANCE: One of the major drawbacks of using ethnomedicinal data to direct testing of plants which may find pharmaceutical use is that certain plants without bioactivity might be traditionally used. An accepted way of highlighting bioactive plants is to compare usage in different cultures. This approach infers that presumed independent discovery by different cultures provides evidence for bioactivity. Although several studies have made cross-cultural comparisons, they focussed on closely related cultures, where common patterns might be the result of common cultural traditions. The aim of this study was to compare three independent ethnomedicinal floras for which similarities can be more robustly interpreted as independent discoveries, and therefore likely to be indication for efficacy. MATERIALS AND METHODS: Data from the literature were compiled about the ethnomedicinal floras for three groups of cultures (Nepal, New Zealand and the Cape of South Africa), selected to minimise historical cultural exchange. Ethnomedicinal applications were divided in 13 categories of use. Regression and binomial analyses were performed at the family level to highlight ethnomedicinal "hot" families. General and condition-specific analyses were carried out. Results from the three regions were compared. RESULTS: Several "hot" families (Anacardiaceae, Asteraceae, Convolvulaceae, Clusiaceae, Cucurbitaceae, Euphorbiaceae, Geraniaceae, Lamiaceae, Malvaceae, Rubiaceae, Sapindaceae, Sapotaceae and Solanaceae) were recovered in common in the general analyses. Several families were also found in common under different categories of use. CONCLUSIONS: Although profound differences are found in the three ethnomedicinal floras, common patterns in ethnomedicinal usage are observed in widely disparate areas of the world with substantially different cultural traditions. As these similarities are likely to stem from independent discoveries, they strongly suggest that underlying bioactivity might be the reason for this convergent usage. The global distribution of prominent usage of families used in common obtained by this study and the wider literature is strong evidence that these families display exceptional potential for discovery of previously overlooked or new medicinal plants and should be placed in high priority in bioscreening studies and conservation schemes.