Tetrahymena as a valuable genetic unicellular animal model organism

 

Tetrahymena thermophila belongs to the Alveolates, a major evolutionary branch of eukaryotic protists composed of three primary lineages: Ciliates (e.g., Tetrahymena and Paramecium), Dinoflagellates (e.g., Symbiodinium, the coral endosymbiont, and Alexandrium, which causes paralytic shellfish poisoning) and the exclusively parasitic Apicomplexa (e.g., Plasmodium falciparum, the causative agent of malaria). Tetrahymena thermophila is a ciliated protozoan belonging to a free-living, fresh-water genus that is highly successful ecologically. No free-living alveolate genome has been sequenced.

 

Since 1923, when Nobel Laureate Andre Lwoff succeeded in growing Tetrahymena in pure culture, two sibling species of the genus Tetrahymena (pyriformis and thermophila) have been used as microbial animal models. With the development of genetic methods in T. thermophila in the 1950's, this has become the species of choice throughout the field.

 

Tetrahymena has typical eukaryotic biology. Its ultrastructure, cell physiology, development, biochemistry, genetics, and molecular biology have been extensively investigated. This organism displays a degree of cellular structural and functional complexity comparable to that of human and other metazoan cells. Consistent with this, analyses of mRNA complexity and very recent EST projects have confirmed that, at the molecular level, Tetrahymena's rich and complex genome conserves a rich set of ancestral eukaryotic functions. In addition, Tetrahymena’s special elaborations of certain basic eukaryotic mechanisms have facilitated discoveries opening the door to major new fields of fundamental research, including:

- First cell whose division was synchronized, leading to the first insights into the existence of cell cycle control mechanisms.

- Identification and purification of the first cytoskeletal motor, dynein, and determination of directional activity.

- Participation in the discovery of lysosomes and peroxisomes.

- One of earliest molecular descriptions of programmed somatic genome rearrangement.

- Discovery of the molecular structure of telomeres, telomerase enzyme, the templating role of telomerase RNA and their roles in cellular senescence and chromosome healing.

- Nobel-prize winning co-discovery of catalytic RNA (ribozymes);

- Discovery of the function of histone acetylation in transcription.

 

The richness of Tetrahymena's biology makes it a genetic unicellular animal model organism "for all seasons." An impressive array of novel molecular genetic technologies places Tetrahymena at the forefront of experimental, in vivo functional genomics research, and complements a wealth of favorable biological features. Availability of the Tetrahymena genome sequence will have major benefits in molecular bioscience and biotechnology. Areas of impact include 1) fundamental biological and biomedical research; 2) finding the function of predicted human genes with homologs in Tetrahymena but not in yeast; 3) value for experimental functional genomics and 4) informing the biology of other alveolates, including pathogens of major medical or agricultural significance. These areas of impact are described in greater detail in the Appendix of the Concept Paper submitted to the Trans-NIH NonMammalian Models Committee in November 2001.

 

Updated 2/02