Institute of Information Science, Academia Sinica

Alternative splicing (AS) is a major post-transcriptional regulatory mechanism to increase proteome diversity and regulatory complexity. This regulatory mechanism is highly developed in complex organisms, and is involved in a wide spectrum of biological processes. The versatility of AS in gene regulations is reflected in its complicated correlations with protein sequence evolution. Firstly, AS can change the compositions of protein sequences. The protein subsequences that are always included in different isoforms and those that are not have significantly different evolutionary rates. Secondly, AS-related changes in protein subsequences usually correspond to changes in the level of protein structural disorderness. Unexpectedly, however, AS and protein structural disorderness have independent effects on the evolution of protein subsequences. Thirdly, the selective constraint on fine-scale protein structural stability has significant effects on the patterns of AS – alternative protein regions that are next to each other tend to co-occur if their boundary overlaps a “protein unit” (i.e., compact building units in three-dimensional protein structures). These observations indicate that AS has played an important, multi-faceted role in the genome evolution of complex organisms. The correlations between AS and other transcriptional/translational regulatory mechanisms and the corresponding selective constraints are worth further explorations.