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Computational identification of regions that influence activity of transposable elements in the human genome

As the most abundant active transposable elements, Alu elements have 1.1 million copies and occupy 6% of the human genome. Recent evidence indicates that 22 AluY and 6 AluS subfamilies have been the most active Alu elements in recent human history, whose transposition has been implicated in several inherited human diseases and in various forms of cancer by integrating into genes; therefore, understanding the transpositional activity and factors that change the activity level of these TEs is very important. There has been some work done to quantify and analyze the transposition of active Alu transposable elements in mobile assays. Based on this activity data, a method/simulation was created in this paper to computationally identify the regions on a TE consensus sequence that may change the transpositional activity. This method was applied to AluY, the youngest and most active Alu subfamily, to identify the harmful regions laying in its consensus. Mutations occurring within these regions have crucial effects in decreasing the elements' transposition. The identified regions were then verified by the secondary structure of the AluY RNA, where the harmful regions overlapped with the AluY RNA major SRP9/14 contact sites. An additional simulation also showed that the identified harmful regions covering the AluY RNA functional regions is not by chance. Therefore, we conclude that mutations occurring within the harmful regions identified alter the mobile activity levels of active AluY elements.