![]() Although natural genes have the potential for direct transfer from one organism to another because of the universality of the genetic code, many such sequences would express poorly when moved into a new organism because of differences in codon usage, GC content, or the presence of expression-limiting regulatory elements 13, 14. Using DNA synthesis to transfer synthetic gene sequences from one organism to another may succeed where transferring natural gene sequences would fail. The growing field of synthetic biology also drives gene transfer because the genome sequences of non-model organisms present a treasure trove of potentially novel and orthogonal genes for testing in model organisms 11, 12. More recent biological research focused on mammalian models has featured considerable introduction of bacterial genes, notably the targeted genome editing tool CRISPR-Cas9 6– 8 and tools for optogenetics 9, 10. Soon afterwards, biologists began sourcing genes encoding thermostable polymerases 4 from thermophilic bacteria and the well-known green fluorescent protein (GFP) 5 from the jellyfish as research tools. In the first industrial example of recombinant DNA technology, Eli Lilly and Genentech expressed a synthetic gene encoding human insulin in the model bacterium Escherichia coli for drug manufacturing 3. We provide empirical evidence that gene synthesis is leading biologists to sample more broadly across the diversity of life, and we provide a foundational tool for the biosurveillance community.īiologists and bioengineers often transfer genes across organisms to test genetic hypotheses or to endow their favorite model organisms with novel traits or functionality 1, 2. Phylogenetic analysis of distance between source and expression organisms reveals that researchers are using synthesis to source genes from more genetically-distant organisms, particularly for longer genes. We then classify ∼19,000 unique genes from the Addgene non-profit plasmid repository to investigate whether natural and synthetic genes have differential use in heterologous expression. This technique, grounded in codon theory and machine learning, can correctly classify genes with 97.7% accuracy on a novel data set. In this paper, we introduce a bioinformatics technique for determining whether a gene is natural or synthetic based solely on nucleotide sequence. Gene synthesis enables creation and modification of genetic sequences at an unprecedented pace, offering enormous potential for new biological functionality but also increasing the need for biosurveillance. ![]()
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