%0 Journal Article %T The complexity of simplicity %A Scott N Peterson %A Claire M Fraser %J Genome Biology %D 2001 %I BioMed Central %R 10.1186/gb-2001-2-2-comment2002 %X Attempts to define life have touched nearly every scientific discipline and have been a long-standing subject in philosophy. Even when limited to the realm of biology, the definitions of life fall short of universal agreement and remain a widely debated subject. The practice of reductionism, whereby life is considered solely from the perspective of the genetic material, also generates controversy and complications. Many of these complications have been appreciated recently as a result of the large-scale application of whole-genome sequencing to microbes. The specific issue we discuss here is an attempt to define the minimum number of genes or functions necessary to support cellular life. The appeal of this subject lies largely in the fact that it represents a fundamental question in biology.We have approached the concept of a 'minimal genome' in a manner not unlike that taken by physicists interested in understanding the nature of the universe: we have relied on an underlying assumption or guiding force that states that a simple set of rules must exist. The difficulty lies in finding the proper way to strip away the outer layers of complexity in order to uncover what is truly general and therefore satisfactorily describes all things. It is our belief that some set of basic parameters and principles are common to all cellular life on this planet. On the surface, especially in the age of genomics, it would appear that we will indeed be able to draw inferences and define commonalities. The advent of whole-genome shotgun sequencing [1] has changed biology in ways that we will not fully appreciate for many years to come. Advances in functional genomics, structural genomics and computational biology have also contributed greatly to our ability to make 'sense' of the huge quantities of DNA sequence data being generated. As we begin to apply these methodologies to the question of the minimal genome, we are faced with new perspectives which emphasize that, like any good scie %U http://genomebiology.com/2001/2/2/comment/2002