The Tetrahymena Kinome

As part of the sequencing and analysis of the first ciliate genome, we performed an initial analysis of the Tetrahymena thermophila kinome. The results are summarized in the Tetrahymeana genome paper:
Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a model eukaryote.
J. A Eisen et al. (2006)
PLoS Biology 4 (9): e286 (Free Full Text)
This analysis was updated in summer of 2009 as part of a comparative study with the kinome of Paramecium tetraurelia, which should be cited as follows:
The ciliate kionme: comparison of the protein kinases of Tetrahymena thermophila and Paramecium tetraurelia
Sara Achour & Gerard Manning In preparation.

Highlights of the Tetrahymena Kinome

Several characteristics make the Tetrahymena genome - and kinome - quite unusual. For one, it is a eukaryote, but only very remotely related to humans (Tetrahymena and other ciliates are members of the kingdom Alveolata, distinct from both animals/fungi and plants), so genes are accordingly very divergent. For another, it is single-celled but large (up to 50 um long) and complex (some 27,000 predicted protein coding genes, similar to that of the human genome).

Within the predicted gene set, we count 1069 predicted protein kinases, the largest number, and the largest fraction of the proteome (3.9%) for any kinome to date. This number is very preliminary, as many encode only fragments of kinase domains - at least 11 pairs should probably fused into single genes - and many other even shorter kinase domain fragments have been set aside for now.

Only 416 kinases (39%) can be classified into previously-known classes, leaving a record 653 kinases that fall into 41 new tentative families (a few have homologs in plants or other distant organisms, but most are ciliate-specific for now).

Casting light on the early evolution of protein kinases

The Dictyostelium kinome revealed a surprising number (24) of kinase subfamilies shared with metazoans, but missing from yeast, which is closer to metazoans than is Dicty. That strongly suggested that yeast had lost many kinases, and some of these reflected yeast biology - loss of kinases involved in splicing and motility, for instance. Dicty, fungi and metazoans are all proposed members of the Unikont group, so Tetrahymena gives us our first view outside of this group, and cast light on an even earlier time in evolution. By comparing kinase subfamilies between organisms, we see that: For more details, see Table 5 from the Tetrahymena paper and Table 1 from the Dictyostelium paper.

Ciliate specialities

As well as the 61% of kinases that are currently unique to ciliates, Tetrahymena also has extensive expansions of several well-known kinases classes (Table 5). The expansions of mitotic kinase classes Aurora (15 kinases), CDC2 (11) and PLK (8) correlates with the complex two-nucleus biology. The NEK family is also expanded (39 members) and has roles both in chromosomal segregation and in control of the many distinct cilia found throughout the body (Wloga et al PMID:16611747). The enormous expansions of 52 ULK members and 83 histidine kinases remain functionally obscure.

All Tetrahymena sequences and classification are now available through our KinBase database, where domain structures and alignments can also be generated.

Much more information is available at the Tetrahymena Genome Database, including a useful introduction to ciliate genetics and biology.