Thursday, January 29, 2015

Titin gene in Fugu - 3 copies or annotation and assembly error?

My growing obsession with the TITIN gene is hopefully not a sign of something else.

The Fugu genome was sequenced, assembled and released soon after the human genome. As was customary during the release of genomes at the beginning of the genomic era it was released with much fanfare. It was flaunted as a good model for comparing synteny with the Human genome. Analysis of the Fugu genome has also been used to find evidence for whole genome duplication in Ray-Finned fish

Titin has two copies, ENSTRUT00000001472 flanked by enox1 and AIM29 [Altered Inheritance rate of Mitochondria] (annotated as 1 of 2) and ENSTRUG00000003764 flanked by TTNB and ubiquitin-conjugating enzyme E2G 2 (TTN 2 of 2). So this suggests the Fugu genome has 3 copies of the Titin gene, if one considers the TTNB gene as the third copy. 

Existence of two adjacent copies of the Titin gene in Zebrafish has been validated by multiple methods. This can also be seen reflected in the latest release of the assembly. TTNA (ENSDARG00000028213) and TTNB (ENSDARG00000000563) are atleast 93 and 82 Kb long. 

The African clawed frog has a different view of things with the TTN gene (ENSXETG00000015021) followed by the TN (Titin Novex-3 or ENSXETG00000024421) gene. While the TTN gene is ~94 Kb long, the Tn gene is annotated as a paralog and has a length of ~15Kb. 

A rather complex history of duplication, retention and loss of this gene which also happens to be the longest known gene makes its annotation and study all the more difficult. Functional characterization of the various orthologs, paralogs and isoforms might be a way forward to understand and distinguish assembly/annotation errors from real biology. 

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