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Advantages of a Minimal Genome

As the complexity of synthetic biology projects increases, extraneous proteins and other gene products inside cells could interact unfavorably with new synthetic pathways. Minimizing a genome would eliminate the unknown by only including parts with a known function; simplifying synthetic engineering. Listed below are a few of the advantages of using a minimal or reduced genome over a wild-type genome.

1) Improved gene stability Gene stability in reduced genomes has been improved by removing transposable elements (TEs), error prone DNA polymerases and the enzymes responsible for the SOS response. Deleterious DNA (like insertion sequences) can disable genes by inserting themselves unfavorably within the genome. An increase in the number of random genetic changes is extremely harmful toward a minimal cell lacking a number of redundant systems.[1][4] Even cells with a small number of TEs could have up to 3.9% of its genes disabled at any one time.[5] A stable genome is a very desirable trait for research and experiment replication.[6][7]

2) Less extraneous gene products Smaller amounts of extraneous gene products, like secondary metabolites, would simplify and reduce the cost of extraction and purification of cell parts, biomolecules and pharmaceuticals, many of which would be more expensive and time consuming to separate from a population of cells by conventional means.[6] Also, production of extraneous metabolites decreases the rate of cellular growth by investing energy into building these products.


Minimal/Clean Genomes vs. Wild Type Genomes

Cells with reduced genomes have less relative fitness than similar wild type cells and cannot easily cope with changes in its environment. For example, reduced cells derived from E. coli MG1655 are more sensitive to reactive oxygen species, even when the cells still retain the genes needed to respond towards oxidative stress. [7]

The mutation rate in cells with minimal genomes is significantly reduced compared to wild type genomes.[7] This would decrease the genetic diversity of the reduced genome cell population. Due to the lack of genetic diversity, it could be plauible that if a bacteriophage ever infected a reduced or minimal genome line, then the cells will be totally destroyed. Otherwise, a reduced mutation rate is a very desirable trait for genome stability.

Estimating the Number of Essential Genes


Comparative Genomics

Comparative genomics looks for homologous sequences of DNA between different organisms and strains (Homologous sequences are when two or more DNA strands from different strains or organisms are very similar or homologous). Genetic homology over a wide number of similar organisms could be an indicator of essential genes since they were conserved throughout those strains or species.[1][6]

A comparative approach could underestimate the number of essential genes since it only accounts for true genetic orthologs. For example, this gene estimate would not account for genes with different DNA sequneces that code for functionally similar gene products.[9][10] In some instances, it could also overestimate the number of essential genes since homologous genes do not have to be useful or essential. For example, virulence factors that are homologous in many pathogenic microbes are not essential genes. [6]

Gene Disruption using Transposable Mutagenesis

Targeted gene disruption using transposable mutagenesis uses transposable elements to inactivate genes. Theoreticlly, if a transposable element is unable to insert itself into a gene, then that gene could be more essential to the cell than other genes that are susceptible to disruption.[11]


mRNA Disruption using Antisense RNA



Genome Reduction

One of the most straightforward approaches to determining a minimal gene set is to reduce the number of genes in a cells genome until it can no longer survive. Reduction would be able to definitively determine the essentiality of trans and cis regions of DNA inside a chromosome. Unfortunately, genome reduction would take a longer time to accomplish since determining a minimal gene set through genome reduction involves, relatively, more trial and error than the other aforementioned methods.

One of the largest reduced, viable cells to date is a modified E. coli MG1655 that has had over 1.8 Mb (38.9%) of it's genome successfully removed.[7]

Genome Synthesis

Whole genome assembly is the creation of an artificial genome, with the intent to install that genome into a pre-existing cell. The new genome is assembled in steps, starting with relatively short (~1000bp) sequences that are then assembled into larger and larger pieces. Synthesis of an artificial bacterial genome has been achieved twice: the first was the complete synthesis of the Mycoplasma genitalium genome[14], followed by the complete synthesis (and transplantation into another cell) of M. mycoides[15]. A notable synethic genome that has been planned is M. laboratorium, which will features a reduced genome, and is being worked on by the J. Craig Venter Institute.[16].

Genome synthesis has been prohibitive in the past because of its high cost but, fortunately, the cost of DNA synthesis has decreased in the past few years.

Methods for Genome Reduction and Synthesis

Systematic Genome Reduction




Explanation of Methods used in Genome Reduction



Selection for Reduced Genome


Mycoplasma mycoides genome synthesis strategy
Mycoplasma mycoides genome synthesis strategy


Minimal Genome Synthesis

For more details, see: DNA Assembly


Mycoplasma mycoides Synthesis


Image of M. genitalium that contain synthetic genomes.
Image of M. genitalium that contain synthetic genomes.

iGEM Connection

An iGEM team from Korea created a program to analyze genomes to help find a minimal genome. Their definition of a minimal genome states that a minimal genome is a set of genes that every living organism contains; a comparative genomics approach. They plan on using this software to design their own minimalistic genome.




  8. May T and Okabe S. . pmid:21980953. PubMed HubMed [May2011]




  16. Glass JI, Assad-Garcia N, Alperovich N, Yooseph S, Lewis MR, Maruf M, Hutchison CA 3rd, Smith HO, and Venter JC. . pmid:16407165. PubMed HubMed [glass2006]
  18. Lee MC and Marx CJ. . pmid:22589730. PubMed HubMed [Lee2012]
All Medline abstracts: PubMed HubMed
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