3. Making sense of genes and genomes

While DNA sequencing is faster and cheaper than ever before, genome assembly remains a significant challenge. ‘Making sense of genes and genomes’ explores how laboratory and computational methods are used in combination to elucidate the true physical nature of DNA molecules inside living cells, and how genes are identified among the vast quantities of chemical letters making up an organism’s genome. It begins with shotgun sequencing—a method that has stood the test of time in balancing efficiency and accuracy. It then considers the problems and solutions of genome assembly; gene finding with transcriptomics; the BLAST algorithm; how to find where proteins carry out their functions; and genome re-sequencing.

2. How to read the book of life

For all its biological importance, DNA is a fragile molecule so extracting it is a difficult process. ‘How to read the book of life’ explains the techniques required to sequence DNA. It begins by explaining the techniques developed for protein and RNA sequencing by Frederick Sanger, Robert Holley, and Carl Woese that were then developed further for DNA sequencing. Following the success of the Human Genome Project, the next generation of DNA sequencing was developed in the mid-2000s. Pyrosequencing was capable of generating orders of magnitude more data at a fraction of the cost, but was superceded within a decade by semiconductor sequencing, reversible chain-termination sequencing, and single-molecule sequencing.

5. Evolutionary genomics

We are still learning how to make sense of what genome sequences have to tell us. ‘Evolutionary genomics’ first considers the ‘molecular clock’, a bedrock concept underlying modern comparative genomic research. Molecular clocks can be inferred using both protein (amino acid) and DNA (nucleotide) sequences. It then looks at our understanding of Y-chromosome and mitochondrial DNA evolution before discussing the difficulties of extracting ancient DNA from fossils. Among the most remarkable achievements of ancient DNA research has been the sequencing of nuclear genomes from Neanderthals and other now-extinct human relatives, aiding research into what makes us human. The question of how eukaryotic cells evolved from prokaryotes is also considered.

6. Genomics and the microbial world

Together, molecular biology and genomics have made it possible to explore the diversity and ecology of the 99 per cent of microbes that cannot be cultured in laboratories. ‘Genomics and the microbial world’ considers environmental gene sequencing; metagenomics, the isolation and analysis of large DNA fragments taken directly from the environment; and single-cell genomics and transcriptomics. It also examines the human microbiome; it is now clear that a complex array of factors contribute to the establishment and maintenance of the human microbiome over the course of a lifetime. Bioprospecting in the metagenomics era is also discussed along with the ambitious Genomic Encyclopedia of Bacteria and Archaea project.

4. The human genome in biology and medicine

The initial phase of human genome sequencing is often referred to as ‘the’ Human Genome Project. But there were two different projects, one publicly funded, the other supported by a private company, Craig Venter’s Celera Genomics. ‘The human genome in biology and medicine’ explains that both projects used DNA samples from more than one person. It was not until 2007 that the first genome of a single individual was published. The structure of the nuclear DNA and mitochondrial genome is also described. Genomics research is having a profound impact on our understanding of the genetic, biochemical, and cell biological underpinnings of cancer, and how it can be detected and treated.

1. What is genomics?

The term ‘genome’ is used to refer to the sum total of DNA inside the single or multiple cells that make up an organism. Complex organisms often have more than one genome. ‘What is genomics?’ looks at the biology of the two main types of cells—prokaryotes and eukaryotes—and explains the double-helix structure of DNA. There are four bases in DNA—adenine (A), cytosine (C), guanine (G), and thymine (T)—and their specific chemical characteristics govern how the two strands of the double helix interact. To completely sequence an organism’s genome is to determine the precise order of all of the As, Cs, Gs, and Ts in its DNA.

7. The future of genomics

‘The future of genomics’ explores some of the ways in which genome science will continue to expand the frontiers of human knowledge, as well as change our world and the way we interact with it. Important ethical, legal, and social issues have already been raised. Who owns your genome sequence and who has the right to access the information it contains? Should it be legal to make ‘designer babies’ by editing the DNA of human embryos? Should we bring extinct species back to life and introduce them into the wild? As genomics-enabled personalized and reproductive medicine become increasingly commonplace, such questions will no longer be hypothetical.