A culture of Escherichia coli in a petri dish doesn’t look like much. To the naked eye, these gut bacteria are white blobs, the kind of thing you would expect to find after neglecting your lunchbox for a few days.
However, these unassuming microbes have been the subject of intense research in the fields of genetic engineering and synthetic biology. By tinkering with their genetic code, scientists around the globe are working towards solving big problems that baffle us – from cancer treatment to the climate emergency.
Earlier this month, in a supposedly landmark achievement, a team led by Jason Chin, a molecular biologist at the University of Cambridge, reported successfully creating the first set of E. coli bacteria with a completely synthetic and radically altered genetic code.
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This means all of this E. coli‘s DNA has been created from scratch. Chin and his colleagues at England’s Medical Research Council Laboratory of Molecular Biology used a computer program to write the code, which they have claimed is more ‘efficient’ than the one found in naturally occurring E. coli.
Then they ordered the DNA building blocks that would physically make up this genetic sequence from a supplier. These parts were used to replace the original genetic code with the lab-made version.
Wait, what?
DNA is the literal stuff of life. It’s what encodes your genes and determines a lot about you, from your eye colour to your predisposition to mental illnesses. The set of all your genes taken together is called a genome.
Every cell in the human body contains the complete set of genes that make up your genome. Your genes are located along the 23 chromosomes in these cells and encoded by deoxyribonucleic acid, or DNA.
In effect, DNA is the molecule that carries all your genetic information. It is made of smaller components called nucleotides. The molecular stores and transmits information through its two nucleotide strands that wrap around each other to form a double helix.
And if you think of the DNA double helix as a spiral staircase, then each step is a hydrogen bond that connects nitrogenous bases on either strand with each other.
There are four kinds of bases: cytosine (C), guanine (G), adenine (A) and thymine (T). The order of these bases along a single strand of DNA makes up the genetic code.
To go with an imperfect writing analogy, if chromosomes make up a sentence, the genes along the chromosomes are the words making up that sentence. And your DNA is the alphabet, with the A, T, G and C as its only letters.
This alphabet is read in sets of three, called codons. Individual codons code for specific amino acids and a sequence of amino acids form a protein. Proteins are what carry out all the functions of life. For example, the AGC codon codes for the amino acid called serine.
The genetic code is universal, meaning all organisms on earth use the same code for the most part. It’s also kind of wasteful, meaning multiple codons code for the same amino acid. For example, serine is also coded for by TCG and TCA.
Why bother to rewrite code?
There are 20 naturally occurring amino acids. If nature were efficient, it would use 20 codons for 20 amino acids, and one more codon for ‘stop’. Since this is not the case, scientists like Chin have been ‘recoding’ the genetic dictionary to create a more efficient code.
Here, the redundant codons are replaced by codons that can be assigned new functions. So a cell with a recoded genome could potentially be used like a factory to produce useful enzymes and proteins.
Chin and his team replaced every occurrence of the serine codon TCG with AGC; every TCA with AGT; and every TAG (the ‘stop’ codon) with TAA. In all, there were 18,214 replacements.
“There are many possible ways you can recode a genome, but a lot of them are problematic: the cell dies,” Chin told STAT News. Supposedly synonymous codons sometimes make proteins with characteristics that kill the cell.
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He calls the resulting line of E. coli Syn61 for the number of codons it uses, as reported in a peer-reviewed paper. Instead of the standard 64 codons overall, his redesigned E. coli uses 51 codons to make all 20 amino acids and two ‘stop’ codons instead of three.
Syn61 grows to be a little longer than E. coli usually are and also grows much slower. Otherwise, it seems to be doing just fine.
This is the largest synthetic genome ever created. It is also the most number of coding changes that have been made to a genome thus far, Tom Ellis, a synthetic biology researcher at Imperial College London, told The Guardian.
In 2010, a geneticist named Craig Venter and his team had assembled the entire genome of the Mycoplasma mycoides bacteria through recoding. Scientists have also synthesised two of the 15 chromosomes making up the genome of a strain of baker’s yeast.
However, compared to Mycoplasma‘s 1.08 million base pairs and the yeast chromosome’s