As well as comparing numbers of genes, we can also compare sizes of genomes in different organisms. Before making such comparisons, we need to understand how genome size is measured. Genomes are measured in numbers of base pairs, and the yardsticks of genome size are a thousand base pairs (a kilobase, kb), a million base pairs (a megabase, Mb), and a billion base pairs (a gigabase, Gb).

Most viral genomes range in size from 3 kb to 300 kb, but a few are very large. The largest viral genome, found in a virus that infects the amoeba Acanthamoeba polyphaga, is 1.2 Mb. This viral genome contains almost 1000 protein-coding genes, including some for sugar, lipid, and amino acid metabolism not found in any other viruses.

The largest viral genome is twice as large as that of the bacterium Mycoplasma genitalium. At 580 kb and encoding only 471 genes, the genome of M. genitalium is the smallest known among free-living bacteria, those capable of living entirely on their own. The complete sequence of small bacterial genomes has allowed researchers to define the smallest, or minimal, genome (and therefore the minimal set of proteins) necessary to sustain life. Current findings suggest that the small M. genitalium is about two times larger than the minimal genome size thought to be necessary to encode all the functions essential to life.

The genomes of bacteria and archaeons are information dense, meaning that most of the genome has a defined function. Roughly speaking, 90% or more of their genomes consist of protein-coding genes (although in many cases the protein has an unknown function). Bacterial genomes range in size from 0.5 to 10 Mb. The bigger genomes have more genes, allowing these bacteria to synthesize small molecules that other bacteria have to scrounge for, or to use chemical energy in the covalent bonds of substances that other bacteria cannot. Archaeons, whose genomes range in size from 0.5 to 5.7 Mb, have similar capabilities.