Gene synthesis allows biologists to source genes from farther away in the tree of life

Abstract

Abstract:Gene synthesis allows biologists and bioengineers to create novel genetic sequences and codonoptimize transgenes for heterologous expression. Because codon choice is key to gene expression and therefore cellular outcomes, it has been argued that gene synthesis will allow researchers to source genes from organisms that would otherwise have been incompatible, opening up moredistant parts of the tree of life as sources for transgenes. We test if this hypothesis is true for academic biological research using a 10-year data set from Addgene, the non-profit plasmid repository. We observe ~19,000 unique genes deposited to Addgene and classify them by whether they are natural or synthetic using a nucleotide-only technique that we develop here. We find that synthetic genes are an increasing share of Addgene deposits. Most importantly, we find direct evidence that researchers are using gene synthesis to source genes from more genetically-distant organisms, particularly for genes that are longer and thus might otherwise be particularly challenging to express. Thus, we provide the first empirical evidence that gene synthesis is leading biologists and bioengineers to sample more broadly across the rich genetic diversity of life, increasingly making that functionality available for industrial or biomedical advances.peer-reviewed)

Synthetic biology in the clinic: engineering vaccines, diagnostics, and therapeutics

“…Concurrent developments in seamless nucleic acid assembly (Gibson et al, 2010) and large-scale genome editing (Annaluru et al, 2014;Richardson et al, 2017) have allowed scientists to rapidly iterate through numerous genetic designs to optimize system function. Widespread environmental metagenomic sequencing projects have also freed scientists from constraining themselves to parts harvested from culturable organisms and have demonstrably increased their utilization of molecular components from far more diverse sources than previously possible (Kunjapur et al, 2018). In addition to harnessing the fruits of natural evolution, synthetic biologists have used directed evolution, including phage-assisted continuous evolution (Esvelt et al, 2011;Badran and Liu, 2015), and design-driven engineering of proteins, nucleic acids, and gene circuits based on advanced modeling (Lillacci et al, 2018;Nielsen et al, 2016) to select for and create biomolecules and synthetic systems with enhanced function.…”