Human genomes are made of double-stranded DNA arranged in the familiar double-helix formation. However, not all organisms have this arrangement for their genomes, specifically less complex organisms, whose genomes may be composed of single-stranded DNA or RNA. So with several genomic possibilities, why is double-stranded DNA such a good molecule to build a genome? This is a fundamental chemical question about the stability of DNA.
What is a Genome?
A genome is the total amount of genetic material for an organism. The Human Genome Project, completed in 2003, was a worldwide endeavor to identify all of the genes in human DNA. Other objectives of the project were to sequence the 3 billion base pairs of human DNA, and store this information in databases for future analysis. The genomes of common lab organisms, such as yeast (Saccharomyces cerevisiae) and the fruit fly (Drosophila melanogaster) have also been sequenced. The human genome is composed of double-stranded DNA and approximately 20,000 genes. However, this is not the case for all organisms. Retroviruses, such as HIV, are composed of single-stranded RNA, while other viruses, such as the M13 bacteriophage, are composed of single-stranded DNA.
The Structure of DNA
In general, human DNA is made of two strands that run anti-parallel, 5’-3’; it has a phosphodiester (sugar and phosphate) backbone and base pairing via hydrogen bonds within the double helix. The base pairs are the building blocks of DNA. In DNA, adenine forms a base pair with thymine and guanine forms a base pair with cytosine. RNA contains the same bases, except that thymine is replaced by uracil. The base pairs are chemically reactive, because they contain amino groups and carbonyl groups. However, the bases are protected from reacting by the phosphodiester backbone. The hydrogen bonds and base interactions also provide added stability to the backbone.
Why is DNA better than RNA to make stable genomes?
The key feature of RNA is that it has a ribose sugar, which carries a hydroxyl group (OH) in the 2′ position. This is a source of instability, because the hydroxyl group destabilizes and results in hydrolysis, which is a reaction with water that causes a chemical breakdown. DNA does not have a hydroxyl group in the 2’ position. This means that the structure of DNA is more stable and less reactive.
DNA contains the base thymine instead of uracil, so that adenine pairs with thymine and guanine with cytosine. This also contributes to the stability of the DNA molecule. Cytosine is very unstable, and can undergo a deamination reaction, which is the removal of an amino acid. In this reaction, the amino group of cytosine is converted to a carbonyl group and the waste product is uracil. Therefore, in RNA, it becomes difficult for the cell to discriminate between the uracil component of RNA and the uracil waste product of the cytosine deamination reaction.
Cytosine does deaminate to uracil in DNA, but the cell recognizes that uracil should not be present. With DNA, the cell can specifically recognize the aberrant uracil because of the presence of thymine. However, that is not the case with RNA, which lacks thymine.
DNA vs. RNA Summary
DNA is a better genomic building block than RNA for the following reasons:
- Due to the phosphodiester backbone, hydrogen-bonding and other features, DNA has a very stable, protected and unreactive structure.
- The structure of RNA, containing a ribose sugar, makes it more susceptible to hydrolysis (i.e., chemical breakdown).
- DNA has a thymine base instead of uracil. In DNA, the cell can easily identify the uracil product of a deamination reaction, whereas in RNA, it is more difficult for the cell to discriminate between the uracil waste of deamination and the naturally-occuring uracil of RNA.