Celebrating similarities-embracing differences.

Using model systems to gain a better understanding of human disease and the underlying biology is standard in biological research. The power of model systems, however, has never been so great as in recent years with the growing availability of a wealth of genomic data from a variety of animals and plants and the ever more-advanced tools for probing, classifying, and characterizing these resources. There are few better examples illustrating the usefulness of model systems as the material presented at the “Yeast Genetics and Human Disease II” meeting, which took place 3 months ago in Vancouver, Canada (June 24–27, 1999). The meeting, which included talks that covered far more than just yeast as a model system, was undeniably successful. Meeting attendees’ primary complaint, in fact, was the press for time; poster sessions started at 7:45 a.m. and talks ended at 10 p.m. This is a relative standard day for most meetings, except for the very early rise. The complaint, however, was due to the fact that most attendees sat through every single talk, rather than taking breaks here and there. A quick dash out into the hallway for a bathroom break or a coffee refill showed an empty corridor, rather than what is usually seen at meetings—a hallway containing several clustered groups talking about previous presentations, waiting for talks that will come up later in the day, or discussing current or potential collaborations with colleagues. The information presented at the meeting was compelling, though not necessarily for its newness but, rather, for the context of the presentations. The composition of talks and attendees varied widely in terms of system and subtopic studied, but the theme in each session formed a cohesiveness that enabled listeners to appreciate the broader perspective and to see clearly the power gained in utilizing information from a broader spectrum of organisms and tools. Like the first meeting held 2 years ago in Baltimore, this conference held forth the strength of yeast (for the most part, especially in this report, Saccharomyces cerevisiae) as a system to use to understand human disease; but with 2 years time to look at the first completely sequenced eukaryotic genome, there was also an increasing awareness of the differences. Sequence and, potentially, functional homology of genes and proteins are the primary reasons why model systems are at all useful. That genes, proteins, and biological systems share a level of similarity in all organisms can often be taken for granted but just how much similarity different organisms share can sometimes be surprising given their evolutionary distances. Even given this surprising similarity, differences do exist, and as such, extrapolation from one system to another requires caution. The power in using model systems comes from being able to define both the similarities and the differences, and to use these in an intelligent way to best direct the research. Functional similarity has numerous applications, but the relevance of that similarity from one organism to another may be far from complete. Worse, as was pointed out by Geoff Duyk, when considering a particular model organism’s overall relevance to humans, the ease in which that organism can be worked with in the laboratory is generally inversely proportionate to its relevance. But this is overall relevance. Growing understanding of functional similarity and/or homology and the use of this as a tool to direct research in a pinpointed fashion can help one pick and choose when to utilize a system that allows ease at getting at specific aspects of a biological pathway and when a whole organism approach is required to better understand the implications of a genetic change on the organism as a whole, and how that might relate to humans. As previously indicated, the presentations at the Vancouver meeting were classified by their area in biology, for example, cell cycle, RNA metabolism and translation, chromosome and genome stability, and so on. But there were other ways to classify these talks, ways that transcended their biological classifications—making each talk useful from a conceptual standpoint to anyone, no matter their “biological sect.” Experiments from any biological discipline could really fall into three categories: use of a model system to define a disease gene (or unknown gene) function; use of a model system to dissect cellular mechanisms; and use of large data sets to classify and characterize novel genes in known biological systems, pathways, or components. Given yeast, with its complete genome, in conjunction with the plethora of other model organisms, some also with complete genomes (Caenorhabditis elegans and numerous bacteria and archaea), as well as growing sequence data for mouse, human, Drosophila, Arabidopsis, and so on, current advances are and should continue to cross species and disciplinary boundaries, as this can only increase our understanding of general biological systems and our own place within these.