Comparative analysis of genome code complexity and manufacturability with engineering benchmarks

Joseph Riolo,Andrew J Steckl

doi:10.1038/s41598-022-06723-5

Abstract

When knowledge has advanced to a state that includes a predictive understanding of the relationship between genome sequence and organism phenotype it will be possible for future engineers to design and produce synthetic organisms. However, the possibility of synthetic biology does not necessarily guarantee its feasibility, in much the same way that the possibility of a brute force attack fails to ensure the timely breaking of robust encryption. The size and range of natural genomes, from a few million base pairs for bacteria to over 100 billion base pairs for some plants, suggests it is necessary to evaluate the practical limits of designing genomes of similar complexity. This analysis characterizes the complexity of natural genomes, compares them to existing engineering benchmarks, and shows that existing large software programs are on similar scale with the genome of complex natural organisms.

Highlights

When knowledge has advanced to a state that includes a predictive understanding of the relationship between genome sequence and organism phenotype it will be possible for future engineers to design and produce synthetic organisms
Mycoplasma genitalium was originally selected because, at the time, it had the fewest genes of any known organism capable of independent growth but Mycoplasma mycoides and Mycoplasma capricolum were later selected for their faster growth rate
This high level of emphasis, including major research stimulus by National Science Foundation (NSF) in 2019 to understand the “Rules of Life”[7], has resulted in significant practical and academic advancements, such as genome rewriting for streamlined synthesis[8]. Based on his experiences Venter observed that the “genome design’s greatest limitation” is the lack of fundamental knowledge[9]. It is unclear at this time if a predictive understanding of organism phenotype will ever be realized but, if the necessary knowledge is gained, it seems likely that practical applications of synthetic biology would be enabled by technologies such as abstraction, standardization, and d ecoupling[10]

Summary

Introduction

When knowledge has advanced to a state that includes a predictive understanding of the relationship between genome sequence and organism phenotype it will be possible for future engineers to design and produce synthetic organisms. Without complete understanding of the object code, making changes to individual bits, or even encapsulated functions, would present challenges like those experienced by current DNA designers attempting to manipulate base pairs or sequences.

Results

Conclusion