Nowadays, SEVA is a well-established resource for vector architecture and genome engineering of bacteria. We manage hundreds of distribution requests and hold a vast selection of constructs in our database. However, it has been thanks to a thorough scientific effort and to the support of our colleagues and community that we have come this far. To kick off our newly launched blog section, let’s take a walk down memory lane, to our beginnings: how SEVA plasmids were born, and why.
The seed of an idea
We’re in the late 1970s. At that time, the revolution of recombinant DNA had just started, and scientists everywhere were creating their constructs and sequences in their labs. It was then when the first small scale studies with plasmids were performed. There was no global agreement on the protocols, nomenclatures or tools that were being used. But that didn’t limit these researcher’s work, and many achievements were accomplished – until Synthetic and Systems Biology appeared.
The huge development of biological sciences led to the testing of more and more complex genetic scenarios. At this point, each lab created their own plasmids to work with them. Their methods were highly specific for their immediate use, and not optimized (lots of non-essential sequences were maintained). Reproducibility was hard to reach sometimes, as many of these external factors affected the results. And yet, no standardization of protocols and materials could be established!
Until recently, there has been little success in the implementations of fixed formats for plasmid vectors and other genetic tools. Moreover, in bacteria, the trend has been towards an extreme diversification rather than a unified system! According to their rejectors, the main obstacle standardization initiatives face is that a fixed format can limit flexibility. But it also allows interoperability between genetic devices and users, avoiding inaccurate metrology and saving scientific time and resources. Reproducibility and data comparison are essential, especially considering how widely globalized scientific research is. That is why we decided to start the SEVA project in 2013.
SEVA 1.01 (Standard European Vector Architecture) started out as a database collection of plasmid vectors, all assembled in a simple, preformatted arrangement of functional DNA segments: replication origins, antibiotic resistances and cargo modules. All plasmid modules were exchangeable, and suitable for any Gram-negative host. Our goal was to create a standardized plasmid structure and nomenclature that facilitated combinations of functional DNA segments for both the analysis and the engineering of diverse Gram-negative bacteria. To further promote our initiative, we also provided an open distribution of SEVA plasmids for free. We would (and still do!) send up to three of our plasmids to academic researchers and other nonprofit laboratories at no cost.
Overall, the project had great welcoming in the field after its release. It took us only two years to publish an update to the SEVA platform, and by that time, it had received more than 470 vector requests from 25 countries with over 40 citations in the academic literature.
In SEVA 2.02, published in 2015, we boosted our platform capabilities. After fixing some DNA sequence errors that were found in the first version, we improved plasmids’ nomenclature and expanded the vector collection. We encouraged other labs to contribute with their own SEVA plasmids, and created a community of scientists working towards standardization. We also included a new repository section called SEVA-SIB (from SIBling), compromising plasmids that partially comply with the SEVA format, but not completely. And it was in this version that we started working on the adaptation to the SBOL (Synthetic Biology Open Language) format and incorporated some functionalities for virtual assembly and analysis of the vectors in the web interface.
During the years until our next publication in 2019, SEVA platform consolidated itself as a popular source of vectors for bacterial engineering, with an increasing number of users and plasmids requests. More than 2100 SEVA plasmids were distributed to 37 countries, and citations of both 1.0 and 2.0 versions climbed over 390.
In 2019’s SEVA 3.03 we presented an improved web platform that made access to information easier to users and included more plasmids (both canonical SEVA vectors and SEVA-SIB constructs), with additional information that made them fully compatible with the SBOL format. We also started working on the adaptation of SEVA plasmids to both Gram-negative and positive bacteria. This way we provided an useful, expandable and user-friendly resource that opened out Synthetic Biology strategies towards a large variety of bacterial species and therefore towards a larger range of biological research areas.
Not long after that publication, in our latest update in 2020 called SEVA 3.14, we developed interoperability between SEVA plasmids and BioBricks, one of the first platforms that tried to standardize the assembly process of interchangeable DNA parts. BioBricks provides a wide range of interchangeable parts, which combined with the flexibility of SEVA vectors, has boosted our cloning library. SEVA 3.1 vectors, along with a core set of standard SevaBrick primers, allows multipart assembly and exchange of short functional genetic elements with minimal cloning and design effort.
A glimpse of the future
Considering all these updates and developments, we have come a long way with SEVA plasmids in the last few years, but we have no plan of stopping now! Every day we keep working on the next updates, such as including mobile genetic elements in our constructs or making our standard compatible with other databases like the iGEM-based Registry of Biological Parts.
Our goal has not changed over time, but expanded, all towards the same goal: the standardization of synthetic biology.
- Silva-Rocha, R. et al. The Standard European Vector Architecture (SEVA): A coherent platform for the analysis and deployment of complex prokaryotic phenotypes. Nucleic Acids Res. 41, 666–675 (2013).
- Martínez-Garćía, E., Aparicio, T., Goñi-Moreno, A., Fraile, S. & De Lorenzo, V. SEVA 2.0: An update of the Standard European Vector Architecture for de-/re-construction of bacterial functionalities. Nucleic Acids Res. 43, D1183–D1189 (2015).
- Martínez-García, E. et al. SEVA 3.0: An update of the Standard European Vector Architecture for enabling portability of genetic constructs among diverse bacterial hosts. Nucleic Acids Res. 48, D1164–D1170 (2020).
- Damalas, S. G., Batianis, C., Martin-Pascual, M., de Lorenzo, V. & Martins dos Santos, V. A. P. SEVA 3.1: enabling interoperability of DNA assembly among the SEVA, BioBricks and Type IIS restriction enzyme standards. Microb. Biotechnol. (2020). doi:10.1111/1751-7915.13609