Whole genome engineering by synthesis

Whole genome engineering is now feasible with the aid of genome editing and synthesis tools. Synthesizing a genome from scratch allows modifications of the genomic structure and function to an extent that was hitherto not possible, which will finally lead to new insights into the basic principles of life and enable valuable applications. With several recent genome synthesis projects as examples, the technical details to synthesize a genome and applications of synthetic genome are addressed in this perspective. A series of ongoing or future synthetic genomics projects, including the different genomes to be synthesized in GPwrite, synthetic minimal genome, massively recoded genome, chimeric genome and synthetic genome with expanded genetic alphabet, are also discussed here with a special focus on theoretical and technical impediments in the design and synthesis process. Synthetic genomics will become a commonplace to engineer pathways and genomes according to arbitrary sets of design principles with the development of high-efficient, low-cost genome synthesis and assembly technologies.

Efficient de novo assembly and modification of large DNA fragments

Synthetic genomics has provided new bottom-up platforms for the functional study of viral and microbial genomes.The construction of the large,gigabase(Gb)-sized genomes of higher organisms will deepen our understanding of genetic blueprints significantly.But for the synthesis and assembly of such large-scale genomes,the development of new or expanded methods is required.In this study,we develop an efficient pipeline for the construction of large DNA fragments sized 100 kilobases(kb)or above from scratches and describe an efficient method for“scar-free”engineering of the assembled sequences.Our method,therefore,should provide a standard framework for producing long DNA molecules,which are critical materials for synthetic genomics and metabolic engineering.

Inevitability or contingency: how many chromosomes do we really need?

In an essay written by the evolutionary biologist Theodosius Dobzhansky in 1973,he pointed out that "Nothing in Biology Makes Sense Except in the Light of Evolution."An interesting phenomenon in biology is the presence of variable numbers of chromosomes in different organisms.Besides several species,which possess multiple circular chromosomes or simply linear chromosomes (Baril et al. 1989;Suwanto and Kaplan,1989;Jumas-Bilak et al.,1998), most prokaryotes only possess one circular chromosome.In contrast,the genomes of eukaryotic species are usually packaged into linear chromosomes with numbers varying from one to hundreds (Crosland and Crozier,1986;Lukhtanov,2015).