What exactly is a genome? Originally, the term referred to the complete set of chromosomes present in a reproductive cell, like a sperm or an egg, which in the human genome is 23 chromosomes. The word “genome” is almost as old as the word “gene,” and it was coined at a time when chromosomes were thought to consist of densely packed genes lined up one after another.

We know now, however, that chromosomes consist primarily of DNA and associated proteins, and that the genetic information in the chromosomes resides in the DNA. One might therefore define the genome as the DNA molecules that are transmitted from parents to offspring. This definition has the advantage of including the DNA in organisms that lack true chromosomes, such as bacteria and archaeons, as well as eukaryotic organelles that contain their own DNA, such as mitochondria and chloroplasts. But a definition restricted to DNA is too narrow because it excludes viruses like HIV, whose genetic material consists of RNA. Defining a genome as the genetic material transmitted from parent to offspring therefore embraces all known cellular forms of life, all known organelles, and all viruses.

In this first section, we focus on how genomes are sequenced, building on the DNA sequencing technology introduced in Chapter 12.