Introduction: Aquaria fish models of human disease.

Abstract

The complete sequencing of a human genome propelled science into what is often termed the “postgenome era.” From a biological perspective, it is poignant to recognize that the completion of the human sequence also signaled the entry into an era of comparative genomics. Comparative genomic studies using model organisms facilitate our understanding of the common genetic elements associated with phenomena such as stress response, disease and its progression, basic physiological mechanisms, and behavior, all of which may involve both environmental and hereditary components. The scientific power offered by comparative genomics makes it likely that several complete genomes from various vertebrates will be characterized over the next decade. The judicious choice of organisms for detailed genomic analyses—those representing evolutionarily distant relationships and diverse lifestyles—will greatly advance our understanding of life on this planet. No group of investigators is better poised to promote and benefit from comparative genomics than those who work with teleost model systems. Comparing the gene sequences of fish and humans has proved to be informative in determining the variable and constrained (or conserved) regions of proteins. The evolutionary divergence and extreme diversity among bony fishes (>18,000 species, an order of magnitude more than mammals) provide a wealth of vertebrate genomes, each possessing unique and valuable information on protein structure and function. From a biomedical viewpoint, having comparative genetic data from several fishes and mammalian species precludes the need to sequence hundreds of individual human genes to determine regions of allelic drift or domains of protein activity. Probably all possible structure-function combinations have occurred in nature over the past 400 million years; much valuable comparative data might well be gleaned from extant fish species. For these reasons, experimental fish models are attracting increased scientific interest. Ensuring that fish models maintain a robust presence in our national scientific infrastructure, as part of a larger focus on research with nonmammalian models, is of considerable importance to our long-term scientific strength. Many aquaria fish models currently used in biomedical research possess several attractive attributes: (1) ease of generating large numbers of animals; (2) availability of inbred stocks and standard strains; (3) ability to make genetic crosses among phenotypically diverse fish; (4) reasonably well-marked gene maps for some species; and (5) genetic mechanisms that correspond to rodent and human models. This range of advantages has helped to make aquaria fish models attractive as research resources to investigators worldwide. Further development of these models will depend on the amelioration of current infrastructural constraints. We must (1) increase the availability of standard genetic stocks to the scientific community at large; (2) improve development and access of transgenic fish lines and select mutant fish; (3) continue to saturate fish gene maps; (4) further characterize molecular markers and cloned genes as research tools in a variety of scientific disciplines; and (5) Received January 31, 2001; accepted March 30, 2001 *Corresponding author: telephone 512-245-0357; e-mail RWalter@swt.edu Mar. Biotechnol. 3, S1–S2, 2001 DOI: 10.1007/s10126-001-0020-7