Significance of a Tetrahymena Genome Sequencing Project

Tetrahymena is a microbial eukaryote whose genome sequence would be of value to biomedical researchers and to the entire scientific community for the following reasons:

1) Important microbial eukaryote for biomedical research not approachable in yeast.

As a eukaryotic microbe with animal biology, Tetrahymena's genome shares much biology with humans. This includes biology relevant to human disease that is absent in yeast, e.g.:
· Regulated secretion,
· Phagocytosis,
· Phagosome-mediated bacterial pathogenesis,
· Ciliary motility,
· Nuclear subset of apoptosis biology,
· Developmentally programmed deletions.
In a recent study of nearly 100 randomly selected sequence reads in Paramecium (a Ciliate closely related to Tetrahymena), half of the high score BLAST matches to mammalian genes failed to match any yeast genes.
The apparent absence of genome compounding and the high ratio of coding to non-coding sequence (e.g. few and small introns) make it a cost-effective genome to sequence.

2) Experimental advantages for productively exploiting the genome sequence.

Among the non-yeast microbial eukaryotes, Tetrahymena has characteristics that make it most amenable to experimental manipulation. These include:
· Easy, fast and inexpensive growth in axenic culture
· Efficient mutant isolation and genetic analysis
· Exact gene replacement by DNA-mediated transformation and homologous recombination
· Easy maintenance of strains with knock-outs of essential genes
· Efficient antisense repression of genes via insertion into ribosomal RNA
· Cell line maintenance in the frozen state.
Important discoveries have exploited Tetrahymena's advantages, such as:
· Self-splicing/ribozymes,
· Telomeres/telomerase,
· Nuclear HAT/histone function.
Genetic and molecular genome mapping are at an advanced stage.

3) Key evolutionary position for comparative genomic analysis.

Tetrahymena's biological success as a free living animal microbe is likely determined by a fairly complete, generic eukaryotic genome, unabridged by parasitic host dependence (medium-large, 200 Mb, Drosophila size; 1/15 of human or mouse genome size).
Tetrahymena is perhaps the most experimentally manipulable, free-living representative of the Alveolata, a group of "crown" eukaryotes composed of three phyla:
· Ciliates, which include Paramecium, Oxytricha, Euplotes, Stylonichia
· Apicomplexa, f.k.a. Sporozoa, which includes Plasmodium, the causative agent of malaria, and other human pathogens.
· Dinoflagellates, which include causative agents of poisoning by the red tide

4) Important eukaryote for biotechnology and environmental monitoring.

The ability to grow Tetrahymena to high density in industrial scale with 1.5 hr doubling time confers biotech potential for the high level expression of foreign proteins.
For example, the surface protein of the Ciliate Ichthyophthirius ("Ick"), an economically important fish parasite that infects commercial fisheries, has been expressed in Tetrahymena, with the goal of facilitating inexpensive fish immunization.
Tetrahymena's fast growth in simple media makes it useful for
· Testing water and nutrient quality
· Determining the relationship between structure and toxicity within families of man-made compounds (e.g. plastics)
Screening for gene expression patterns on microarrays would greatly facilitate this work.

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