Lessons learned from the introduction of genetically engineered crops: relevance to gene drive deployment in Africa

The application of gene drives to achieve public health goals, such as the suppression of Anopheles gambiae populations, or altering their ability to sustain Plasmodium spp. infections, has received much attention from researchers. If successful, this genetic tool can contribute greatly to the wellbeing of people in regions severely affected by malaria. However, engineered gene drives are a product of genetic engineering, and the experience to date, gained through the deployment of genetically engineered (GE) crops, is that GE technology has had difficulty receiving public acceptance in Africa, a key region for the deployment of gene drives. The history of GE crop deployment in this region provides good lessons for the deployment of gene drives as well. GE crops have been in commercial production for 24 years, since the planting of the first GE soybean crop in 1996. During this time, regulatory approvals and farmer adoption of these crops has grown rapidly in the Americas, and to a lesser extent in Asia. Their safety has been recognized by numerous scientific organizations. Economic and health benefits have been well documented in the countries that have grown them. However, only one transgenic crop event is being grown in Europe, and only in two countries in that region. Europe has been extremely opposed to GE crops, due in large part to the public view of agriculture that opposes “industrial” farming. This attitude is reflected in a highly precautionary regulatory and policy environment, which has highly influenced how African countries have dealt with GE technology and are likely to be applied to future genetic technologies, including gene drives. Furthermore, a mistrust of government regulatory agencies, the publication of scientific reports claiming adverse effects of GE crops, the involvement of corporations as the first GE crop developers, the lack of identifiable consumer benefit, and low public understanding of the technology further contributed to the lack of acceptance. Coupled with more emotionally impactful messaging to the public by opposition groups and the general tendency of negative messages to be more credible than positive ones, GE crops failed to gain a place in European agriculture, thus influencing African acceptance and government policy. From this experience, the following lessons have been learned that would apply to the deployment of gene drives, in Africa:

It will be important to establish trust in those who are developing the technology, as well as in those who are making regulatory decisions. Engagement of the community, where those who are involved are able to make genuine contributions to the decision-making process, are necessary to achieve that trust. The use of tools to facilitate participatory modeling could be considered in order to enhance current community engagement efforts.

Trusted, accurate information on gene drives should be made available to the general public, journalists, and scientists who are not connected with the field. Those sources of information should also be able to summarize and analyze important scientific results and emerging issues in the field in order to place those developments in the proper context. Engagement should involve more opportunities for participation of stakeholders in conceptualizing, planning, and decision-making.

Diversifying the source of funding for gene drive research and development, particularly by participation of countries and regional bodies, would show that country or regional interests are represented.

Efforts by developers and neutral groups to provide the public and decisionmakers with a more thorough understanding of the benefits and risks of this technology, especially to local communities, would help them reach more informed decisions.

A better understanding of gene drive technology can be fostered by governments, as part of established biosafety policy in several African countries. Developers and neutral groups could also be helpful in increasing public understanding of the technology of genetic engineering, including gene drives.

Effective messaging to balance the messaging of groups opposed to gene drives is needed. These messages should be not only factual but also have emotional and intuitive appeal.

     

Mechanisms of growth inhibition of Phytomonas serpens by the alkaloids tomatine and tomatidine

Phytomonas serpens are flagellates in the family Trypanosomatidae that parasitise the tomato plant (Solanum lycopersicum L.), which results in fruits with low commercial value. The tomato glycoalkaloid tomatine and its aglycone tomatidine inhibit the growth of P. serpens in axenic cultures. Tomatine, like many other saponins, induces permeabilisation of the cell membrane and a loss of cell content, including the cytosolic enzyme pyruvate kinase. In contrast, tomatidine does not cause permeabilisation of membranes, but instead provokes morphological changes, including vacuolisation. Phytomonas treated with tomatidine show an increased accumulation of labelled neutral lipids (BODYPY-palmitic), a notable decrease in the amount of C₂₄-alkylated sterols and an increase in zymosterol content. These results are consistent with the inhibition of 24-sterol methyltransferase (SMT), which is an important enzyme that is responsible for the methylation of sterols at the 24 position. We propose that the main target of tomatidine is the sterols biosynthetic pathway, specifically, inhibition of the 24-SMT. Altogether, the results obtained in the present paper suggest a more general effect of alkaloids in trypanosomatids, which opens potential therapeutic possibilities for the treatment of the diseases caused by these pathogens.     

1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium-regulating Components

1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃) plays an integral role in calcium homeostasis in higher organisms through its actions in the intestine, kidney, and skeleton. Interestingly, although several intestinal genes are known to play a contributory role in calcium homeostasis, the entire caste of key components remains to be identified. To examine this issue, Cyp27b1 null mice on either a normal or a high calcium/phosphate-containing rescue diet were treated with vehicle or 1,25(OH)₂D₃ and evaluated 6 h later. RNA samples from the duodena were then subjected to RNA sequence analysis, and the data were analyzed bioinformatically. 1,25(OH)₂D₃ altered expression of large collections of genes in animals under either dietary condition. 45 genes were found common to both 1,25(OH)₂D₃-treated groups and were composed of genes previously linked to intestinal calcium uptake, including S100g, Trpv6, Atp2b1, and Cldn2 as well as others. An additional distinct network of 56 genes was regulated exclusively by diet. We then conducted a ChIP sequence analysis of binding sites for the vitamin D receptor (VDR) across the proximal intestine in vitamin D-sufficient normal mice treated with vehicle or 1,25(OH)₂D₃. The residual VDR cistrome was composed of 4617 sites, which was increased almost 4-fold following hormone treatment. Interestingly, the majority of the genes regulated by 1,25(OH)₂D₃ in each diet group as well as those found in common in both groups contained frequent VDR sites that likely regulated their expression. This study revealed a global network of genes in the intestine that both represent direct targets of vitamin D action in mice and are involved in calcium absorption.     

A revision of the genus Muricea Lamouroux, 1821 (Anthozoa,Octocorallia) in the eastern Pacific. Part I: Eumuricea Verrill, 1869 revisited

Muricea is an amphi-American genus. Verrill proposed dividing the species from the Pacific Ocean into three genera and established the genus Eumuricea for five eastern Pacific species with tubular calyces. Eumuricea is basically characterized by colonies with elongate, cylindrical calyces with truncate margins and star-like opercula, and the occurrence of unilateral spinous spindles. According to these characteristics, Eumuricea does not show enough difference from Muricea to be treated as a separate genus. Original type material of Eumuricea was morphologically analysed and illustrated using optical and scanning electron microscopy. We conclude that the eastern Pacific species should be placed in the genus Muricea and form a group characterised by tubular calyces that comprises four species at present, Muricea acervata, Muricea hispida, Muricea squarrosa, and Muricea tubigera and a dubious species Muricea horrida. Lectotypes were designated for Muricea squarrosa and Muricea hispida to establish their taxonomic status. The genus Eumuricea has also been misunderstood by former authors who erroneously assigned species to it. For these species we propose new combinations: Swiftia pusilla, Astrogorgia splendens and Astrogorgia ramosa.     

Radial stem variations of Tabebuia chrysantha (Bignoniaceae) in different tropical forest ecosystems of southern Ecuador

Stem diameter increments of the broadleaved deciduous tree species Tabebuia chrysantha were measured with high-resolution dendrometers in a tropical lower montane forest and in a dry forest in southern Ecuador, the latter showing a distinct dry season. Those analyses were complemented by wood anatomical studies on regularly collected microcores to determine the season of active cambial growth and the time of formation of annual growth boundaries. The length of the cambial active period varied between 3 and 7 months at the tropical lower montane forest and 2 and 4 months in the dry forest, respectively. During dry days, amplitudes of daily stem diameter variations correlated with vapour pressure deficit. During October and November, inter-annual climate variations may lead to dry and sunny conditions in the tropical lower montane forest, causing water deficit and stem diameter shrinkage in T. chrysantha. The results of the climate–growth analysis show a positive relationship between tree growth and rainfall as well as vapour pressure deficit in certain periods of the year, indicating that rainfall plays a major role for tree growth.     

Conclusion: applying South East Asia Rainforest Research Programme science to land-use management policy and practice in a changing landscape and climate

The context and challenges relating to the remaining tropical rainforest are briefly reviewed and the roles which science can play in addressing questions are outlined. Key messages which articles in the special issue, mainly based on projects of the Royal Society South East Asia Rainforest Research Programme (SEARRP), have raised of relevance to policies on land use, land management and REDD+ are then considered. Results from the atmospheric science and hydrology papers, and some of the ecological ones, demonstrate the very high ecosystem service values of rainforest (compared with oil palm) in maintaining high biodiversity, good local air quality, reducing greenhouse emissions, and reducing landslide, flooding and sedimentation consequences of climate change-and hence provide science to underpin the protection of remaining forest, even if degraded and fragmented. Another group of articles test ways of restoring forest quality (in terms of biodiversity and carbon value) or maintaining as high biodiversity and ecological functioning levels as possible via intelligent design of forest zones and fragments within oil palm landscapes. Finally, factors that have helped to enhance the policy relevance of SEARRP projects and dissemination of their results to decision-makers are outlined.     

ATAQS: A computational software tool for high throughput transition optimization and validation for selected reaction monitoring mass spectrometry

Background

Copy number variants (CNVs), including deletions, amplifications, and other rearrangements, are common in human and cancer genomes. Copy number data from array comparative genome hybridization (aCGH) and next-generation DNA sequencing is widely used to measure copy number variants. Comparison of copy number data from multiple individuals reveals recurrent variants. Typically, the interior of a recurrent CNV is examined for genes or other loci associated with a phenotype. However, in some cases, such as gene truncations and fusion genes, the target of variant lies at the boundary of the variant.

Results

We introduce Neighborhood Breakpoint Conservation (NBC), an algorithm for identifying rearrangement breakpoints that are highly conserved at the same locus in multiple individuals. NBC detects recurrent breakpoints at varying levels of resolution, including breakpoints whose location is exactly conserved and breakpoints whose location varies within a gene. NBC also identifies pairs of recurrent breakpoints such as those that result from fusion genes. We apply NBC to aCGH data from 36 primary prostate tumors and identify 12 novel rearrangements, one of which is the well-known TMPRSS2-ERG fusion gene. We also apply NBC to 227 glioblastoma tumors and predict 93 novel rearrangements which we further classify as gene truncations, germline structural variants, and fusion genes. A number of these variants involve the protein phosphatase PTPN12 suggesting that deregulation of PTPN12, via a variety of rearrangements, is common in glioblastoma.

Conclusions

We demonstrate that NBC is useful for detection of recurrent breakpoints resulting from copy number variants or other structural variants, and in particular identifies recurrent breakpoints that result in gene truncations or fusion genes. Software is available at http://http.//cs.brown.edu/people/braphael/software.html.