Chapter Introduction

8: Genomes, Transcriptomes, and Proteomes

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  • 8.1 Genomes and Genomics

  • 8.2 Transcriptomes and Proteomes

  • 8.3 Our Genetic History

MOMENT OF DISCOVERY

Joe DeRisi

When the SARS virus emerged as a new infectious disease, at first no one knew what was causing the infection. There were thousands of cases around the world, and because 14% were fatal, it was clearly a public health emergency, especially because we didn’t know at the time if the infection could be contained.

There were two big moments of discovery in my own lab that came about as we worked around the clock to identify the new infectious agent. The first came when we put samples from infected patients on our ViroChip, which contains fragments of conserved DNA sequences from all known types of viruses. I recall watching the spots lighting up on the scanner, and we could see that this new virus had sequences similar to coronaviruses from birds, cows, humans—it was some kind of strange new type of coronavirus that had never been seen before.

The second exciting moment came over the next couple of days as we began working nonstop to clone and sequence bits of the virus genome from the ViroChip array. Sequences were determined by a standard method in which the cloned bits were copied by a polymerase using fluorescently labeled nucleotides. I sat by the sequencer watching as each fluorescent nucleotide was detected, and I wrote down each base by hand because I couldn’t wait for the run to finish to see what the sequences were! This level of intensity doesn’t happen every day—we were not stopping to sleep or rest, surviving off pizza and Skittles, and it was exhausting—but it was so incredibly exciting to be the very first person to see the actual genome sequence of this new infectious agent. That was so fun. And in the end, we had to obtain enough DNA sequence to predict the encoded protein sequences that positively identified this virus as a new and highly divergent coronavirus.

—Joe DeRisi, on his discovery of the SARS virus

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Molecular biologists approach their subject at many levels. With the birth of biotechnology in the 1970s, the focus was on genes—their form, function, transcription, translation, and applications in medicine and agriculture. The new technologies also facilitated countless advances in our understanding of the RNA and protein products of genes. In truth, though, each gene is just a small part of a much larger genome. Understanding individual cellular components requires an examination of their function in the cellular context. At the same time, a host of new molecular questions arise that can be addressed only at the level of an organelle, cell, or organism. How does a cell or organism respond to a change in its environment, and how is the response regulated? How are the replication and transcription of genetic material coordinated with cell division? How can multiple genes be coordinately regulated? How many regulatory, replication, and repair systems for DNA exist in cells, and how does an organism’s lifestyle shape its evolution? Over the past few decades, molecular biology has undergone a constant expansion of its reach. No longer limited to examining one or a few genes or gene products at a time, scientists are addressing problems dealing with increasingly complex and interconnected systems.

The shift was made possible by continuing advances in technology. The sequencing of individual genes has been supplanted by sequencing projects that encompass all of an organism’s DNA—its genome. Examining the changes in the sum of a cell’s RNA and proteins—its transcriptome and proteome—became a practical pursuit. The resulting efforts have spawned the new subdisciplines of genomics, transcriptomics, and proteomics, which now allow us to investigate questions on a cellular, organismal, or population scale. Huge public databases have been established, packed with information about genetic material and gene products, for species almost too numerous to count. Ongoing initiatives range from the customization of medical treatments based on an individual’s genetic makeup to the detailed tracing of human evolution. The subdisciplines and databases we introduce in this chapter are an important legacy of modern molecular biology. They are also a key to its future. Biology in the twenty-first century will move forward with the aid of informational resources undreamed of just a few years ago.