Guide through the blizzard

Biology's dense particularity is criss-crossed with unifying connections. Each of us — student, teacher, or professional scientist — can master the details of a narrow subject and come to see how they hang together. We know very well, also, that the most exciting discoveries reveal connections between one mass of particulars and its near and distant neighbors. Even so, many of us are daunted by the prospect of exploring the apparently trackless wildernesses outside our specialized subject. More and more, we need knowledgeable, thoughtful travel guides — guides much like Genes & Signals, by Mark Ptashne and Alexander Gann. From the bewildering variety of macromolecular interactions that regulate expression of specific genes, Genes & Signals seeks to identify and teach key principles. The book's central litany, stated on page 1 of the introduction and repeatedly thereafter, is that expression of a gene almost always depends upon regulated recruitment to distinct segments of DNA of an appropriate congeries of proteins, each spotted with adhesive surfaces for binding to the others. One advantage of regulated recruitment is that it can confer exquisite specificity on an otherwise non-specific enzyme, like RNA polymerase, by bringing it to the right substrate-in this case, a specific site on the DNA. " Already knew that, " many of us quickly respond. But real understanding of a general principle — as this book teaches us — requires that we see it embodied in specific examples. After the introduction, chapter I (" Lessons from Bacteria " ; 39 pages) describes three major mechanisms of gene regulation in bacteria: regulated recruitment of RNA polymerase (two examples, including expression of lac genes and λ λ lysis/lysogeny), allosteric activation of the polymerase already bound to its promoters (example: NtrC binds to polymerase to regulate genes involved in nitrogen metabolism), and activation of the promoter itself (example: mercury binds to MerR, which in turn activates expression of mercury-resistance genes by altering the conformation of its DNA binding site). In simple diagrams and straightforward prose, the authors describe experimental approaches (such as domain swapping between protein regulators) to distinguish between these mechanisms. Such experiments show, the authors tell us, that regulated recruitment of RNA polymerase to promoter sequences has captured a dominant share of the regulatory market in E. coli. In S. cerevisiae, the authors focus on regulated recruitment in controlling expression of GAL genes (Chapter II, " Yeast: A single-celled eukaryote " ; …