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Genomes fascinate Jeffrey Lawrence. Because microbial cells provide the simplest and best systems for studying genomes and the genes they contain, he concentrates his efforts on bacteria. But they are mere tools. The genomes are what captivate his attention.

``My interests have always been how and why genomes evolved,'' the University of Pittsburgh bacterial evolutionist says. It's the scope and content of the genome that really define what an organism is, he explains. One could think of an organism as ``merely a collection of genes that cooperate to make a vehicle that transmits them.''

We are just at the beginning of answering the fundamental question of why genomes have the genes they have, Lawrence says. His research focuses on how and why genes are gained and lost from genomes. Currently he is studying what maintains some genes in some lineages while the same genes are lost in others, focusing on the genes responsible for recycling the sulfur-containing amino acids. He is also trying to determine how rates of gene transfer may vary among different lineages and for what reasons.

One of Lawrence's first major contributions to the field is the Selfish Operon Model, which he and University of Utah professor John Roth developed during Lawrence's stint as a postdoc in Roth's lab. The term they coined--selfish operon--plays off the idea of the selfish gene popularized by evolutionary biologist Richard Dawkins. Simply put, the selfish operon model suggests that genes cluster in groups to increase their likelihood of being distributed among organisms, whether their functions are essential to those organisms or not.

``It's a long and complex process, how we focused in on it,'' Lawrence says. He and Roth were studying a particular gene cluster that confers a nonessential function--coenzyme B₁₂ biosynthesis--that is widely though sporadically distributed among bacteria. One of the common characteristics of many operons is that some of their gene products do not contribute to basic metabolism, Lawrence points out. Through standard gene acquisition and loss, genes with such peripheral functions logically should be squeezed out in place of more essential genes.

``You might think those genes that are gathered together in groups are those which then could be transferred, and that gives them a small benefit,'' says Lawrence, explaining how he and Roth thought through this issue. ``If you start thinking about it more deeply, you realize that the advantage they gain by potentially being transferred can lead to the cluster in the first place. Not only is ease of transfer a property of existing clusters, but it can provide an incremental benefit for genes that allows them to be clustered in the first place.''

The Selfish Operon Model assumes that lateral gene transfer plays a key role as a selection mechanism, allowing genes that are not associated with one another to wind up next to each other in genomes. ``As soon as you transfer a gene from one place to another, then all the stuff in between is potentially irrelevant and is subject to deletion because it may not be important to the recipient organism,'' he explains. ``The only thing that will be maintained are those genes that potentially confer a function. Everything else will be deleted and the only thing you'll wind up with is an operon. [Recognizing] the role of horizontal transfer actually allowing the physical association of the genes was a pretty incredible step.''

Lawrence concedes that some cases, such as the operons of ribosomal proteins, may not be entirely explainable by the Selfish Operon Model. However, he says, ``I think it is fairly good at explaining [the origin of] classes of gene clusters [such as] some operons and some nontraditional gene clusters like clusters of antibiotic resistance genes or groupings of operons together.'' But horizontal transfer does not provide a means for selecting and maintaining genes once they are in an operon, he notes. ``The structure once formed, if it is in fact maintained, must be useful for some reason, so other models must explain why that operon is being maintained,'' he says. ``I think dissection of properties and determining how and why something arose as opposed to how and why something is maintained, that's where the field should be going.''

Lack of data and context hinders such explorations, however. ``Asking, for example, how and why did the ribosomal cistron evolve is very difficult because it happened very, very long ago,'' Lawrence says. ``There are no data on what those organisms were like, what their population structures were like at that time, so it's really down to wholly untestable hypothesizing.''

Lawrence is not averse to bending his mind around wholly theoretical concepts. For instance, asked to participate in a 1998 National Academy of Science workshop on minimal microbial size (see ASM News, February 1999, p. 68), Lawrence developed a theoretical model of compartments, or meta-cells, which do not have genomes, but rather act like way stations through which nomadic genes pass in and out.

``If you consider gene transfer as really quite a prevalent force, in theory you could imagine a group of cooperative organisms that on average have no genes, that the genes are so rapidly transferred between the compartments, they don't dwell in any one place that long,'' he says. ``So you could in fact reduce the size of the organism enormously if you don't demand that the genome stay resident in the cell 100% of the time.''

Outside the lab, Lawrence keeps his creative juices flowing through music, penning and playing folk jazz tunes with a cadre of fellow scientists who have formed the band Fruit Sniffin' Beagle. Lawrence plays keyboards, guitar, and bass. His diverse musical talents mirror his scientific skills and intellect.

Roth notes that Lawrence's knowledge spans several disciplines. ``Jeff is uniquely placed to bridge the gap between the people who do traditional evolutionary biology, the people who are interested in interpreting genomes, and traditional molecular biologists,'' Roth says. ``Those three groups don't talk to each other very well, but they have to come together if we're going to get the biggest bang out of genome sequencing. Jeff combines knowledge in all three in a way that few other people do.''

Christine Stencel is a science writer and manager in the ASM Communications Department.