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

Abstract

Gene synthesis allows biologists and bioengineers to create novel genetic sequences and codon-optimize 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 more-distant 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.