Introns interrupt our genes most of the time and the production of functional mRNAs requires their efficient and accurate removal. The regulation and accuracy of intron removal is significant as an estimated 15% of human disease-associated point mutations disrupt splicing. In contrast to our intron-rich genome, introns are present in less than 5% of Saccharomyces Cerevisiae’s genes. Most S. Cerevisiae genes that contain introns are involved in growth, division, and homeostasis. The expression levels of these genes should be resistant to random fluctuations to prevent undesirable growth- and division- rates as well as inefficient metabolism. Because it is known that introns can increase the efficiency of expression and that introns are targets of negative regulation as well as auto-inhibition, I am examining the influence introns have on expression variability in yeast.
While the largest yeast intron is only 1,001 nucleotides, mammalian introns can be extremely large and some are greater than 100,000 nucleotides. Notwithstanding that it is unknown what function large introns play, there exists a bias for longer introns being present in tissue- and development stage- specific genes. To better understand the influence of intron length in mammalian genes I am engineering synthetic gene networks that rely on different intron lengths to coordinate gene expression.