How DNA is made

Recently I started a series of posts on whether biological computers are science fact or still science fiction. I started out by saying that DNA is an excellent way to archive information but it still can’t be used to store information that you need to access all the time, like a lot of what you have on your personal computer, because we don’t have the technology to read and write DNA quickly. This goes for either synthetic DNA or natural DNA. Which begs the question – how do we read and write DNA? I’ll go through the writing first because it is more complicated and has more room for improvement. 

How DNA is copied inside cells

Inside living cells, DNA is copied by enzymes called DNA polymerases. Before any cell can divide – from a bacterial cell right up to a human liver cell – the DNA in the nucleus must first be copied. This starts at specific places in the genome called origins of replication. A helicase enzyme splits the DNA helix into two strands. Each strand is then copied.

DNA is made up of four different nucleotides, or DNA letters: A; T; C and G. A can only bind to T and C can only bind to G. So if there is a T in one DNA strand, there must be an A in the same place in the other strand. The two strands are therefore said to be complementary to each other. Like wine and cheese. Or chocolate and caramel.

DNA can only be written in one direction, which for some strange reason is called 5′ (said 5 prime) to 3′. However, the two DNA strands in the helix actually run in opposite directions. So when they are split by helicase, one strand, called the leading strand, can easily be copied by DNA polymerase, but the other strand, called the lagging strand, has to be copied backwards. This means that the cell has to use a different enzyme called a primase to add a small RNA primer to the lagging strand and then a DNA polymerase can copy a small segment of the strand backwards. Then the team of enzymes jumps ahead and copies the next segment.

If you’ve got time here’s a great 6 minute video on DNA replication from Biology/Medicine animations HD:

How DNA is copied in the lab

In the lab we can copy small areas of DNA via a polymerase chain reaction (PCR). To do this we need a small amount of starting DNA extracted from cells or animal tissue, nucleotides (DNA letters), polymerase enzyme, buffer and cations (we usually use MgCl2). DNA is first heated to 95 degrees to separate the two DNA stands. This is called denaturing. It is then cooled so short sequences of nucleotides, called primers, can bind to specific regions of the separated DNA, which is called annealing. One primer binds to each end of the sequence that you want to copy. Then the polymerase enzyme adds nucleotides to the end of each primer, which is called elongation. If you get the PCR recipe right, the reaction can add 1000 bases per minute.

Here’s the same info in video form thanks to Canal Divulgacion (yes I love videos):

How DNA is made from scratch in the lab

DNA is never really made from scratch inside cells. It is always copied from existing DNA. Evolution happens from DNA changes that occur when DNA is miscopied leading to mutations.

However we can make DNA from scratch in the lab. DNA code is designed on a computer then made in a DNA synthesis machine. The DNA synthesis machine contains bottles of modified DNA bases, or letters. A computer tells the machine in which order to assemble the DNA bases. Only short sequences of DNA can be made in this way. So the DNA code needed to make a gene is broken up into short sequences and these are synthesised by the machine. Then a modified polymerase chain reaction is used to stick all the short sequences together into a final double stranded gene product.

Scientists have used this technique to write a completely synthetic genome of the bacteria Mycoplasma mycoides. They inserted the synthetic genome into a different species of bacteria, Mycoplasma capricolum. And the amazing thing is that the recipient cells could grow and divide only using the synthetic genome.

Unfortunately artificial gene synthesis is still slow and expensive. It would take weeks or months and cost millions of dollars to synthesise enough DNA to store the information you have on your computer. This needs to change before we can use DNA to store information in bio computers.

Read the other posts in the bio-computing series here:

Can biological computers become a reality?

Synthetic DNA and living computers

The Scientific Papers:

Gibson et al. Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Science. 2012 (free and open access)

Hughes et al. Gene synthesis: methods and applications. Methods Enzymol. 2011.

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