Here is another thoughtful story by my active, enthusiastic, and outstanding student, Zahraa Hasan.
When I studied alternative splicing in 281 course, the instructor [Hasan] said that the possible combinations are unlimited [exaggeration by Hasan]. I wanted to see if it is truly unlimited or it is possible to calculate it.
I thought that I can calculate it by using permutations and combinations but those approaches did not work. The Permutations did not work because it allows the second exon to become before the first exon, and this is not possible in genes. Combinations did not work because it does not deal with the order. So, I realized that I had to find the formula that can be used for this process by trying every possible combination for the exons. At the end I found it : 2(#of exons – 2). The (-2) is in the formula because the first exon contains the AUG codon (the beginning of the gene), and the last exon contains a stop codon, so a protein cannot theatrically be synthesized if either the first exon or the last exon is not included.
Given:
- The human gene with the largest number of exons is (TTN gene)
- TTN gene has 363 exons.
- TTN gene cDNA size is 82Kb.
- TTN codes for Titin protein.
- TTN protein contains 26,926 amino acids and a mass of 2993kDa.
The theoretical possible combinations of TTN exons would be
2(363-2) = 4.69×10108 possible combinations !!!
This formula can be used only for skipping exons in the alternative splicing process.