Synthetic biology: building new chromosomes from scratch


EXCERPT: . . . Chromosomes are the “hard drives” of cells. They contain most of the cell’s DNA and genes. Bacteria and archaea typically have a single circular chromosome, while eukaryotes contain several linear ones. Besides genetic information, a chromosome contains structural elements. Centromers (that participate in mitosis), telomers (that have a role in maintaining linear chromosome integrity), and origins of replication (that are where DNA replication starts in circular DNA pieces) are some well-known examples.

Artificial chromosomes are chromosomes that have been fully constructed in the lab and assembled within a cell. An important note: artificial chromosomes do not mean artificial life. They function normally within cells and the DNA used is the same as the one found in nature. What is different is their origin – they don’t come from a DNA template duplication – and the genetic information they carry. The advantages of building a chromosome align with both goals of synthetic biology. The role of many DNA elements is unknown. By recombining, adding, or deleting DNA sequences, we can understand if a genetic part is essential and what does it do. By rewriting a genome from scratch, we can obtain a cell with specific properties – and only them! Such cells are invaluable tools for applied and fundamental research.

Current DNA technology makes the construction of short DNA pieces easy and available to most research labs, but the same cannot be said for chromosome assembly. And this is not surprising: a plasmid with a few genes contains a few thousand base pairs; a chromosome several million or billion! [...] A research group from Switzerland designed and assembled a full bacterial chromosome with its genome minimized to the essential components; so far, they haven’t managed to insert the chromosome to the organism. A minimal bacterial cell with a synthetic genome was nevertheless announced in 2016 by J. Craig Venter Institute scientists. And recently the molecular biology workhorse, the bacterium E. coli, got its genome replaced by a synthetic variant.

All these works required a huge amount of resources and faced tremendous challenges. And despite the successes, we are a long way from mastering the craft of genome writing. In a recent article, Nili Ostrov and her collaborators in the field of synthetic genomics outline the technological advances needed to reach this goal. They list the following areas of focus: genome design, DNA synthesis, genome editing, and chromosome assembly. (MORE - details)

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