Alternative splicing is a common mechanism for eukaryotes to expand their repertoire of gene functions. Studies by Xu and colleagues (2002. Nuc. Acids Res. 30: 3754-3766) indicate that approximately 50 percent of human genes use alternative splicing, and approximately 15 percent of disease-causing mutations involve aberrant alternative splicing. Different tissues show remarkably different frequencies of alternative splicing, with the brain accounting for approximately 18 percent of such events. (a) Define alternative splicing and speculate on the evolutionary strategy alternative splicing offers to organisms. (b) Why might some tissues engage in more alternative splicing than others?

Alternative splicing is a process in gene expression that occurs in eukaryotes, allowing a single gene to produce multiple protein variants. It involves the selective inclusion or exclusion of specific exons (coding regions) from the pre-mRNA, resulting in different mature mRNA molecules. These mRNAs then go on to produce different protein isoforms with potentially distinct functions.

Alternative splicing offers several evolutionary advantages to organisms. Firstly, it increases the proteome diversity from a limited number of genes, allowing organisms to create multiple protein variants with unique functions from a single gene. This can help organisms adapt to different environmental conditions, develop distinct tissues with specialized functions, and respond to various cellular signals and regulatory pathways. Moreover, alternative splicing can contribute to the evolution of new functions in existing proteins, as the presence of different protein domains in the various isoforms allows for novel functional combinations.

Certain tissues may engage in more alternative splicing events than others due to the diverse functional requirements of their respective cells. Since different tissues serve specialized purposes and are composed of unique cell populations, they may use alternative splicing to generate the required proteins that serve their specific functions and help in maintaining their cellular processes. For example, the brain is a highly complex tissue with multiple cell types, involved in various functions like information processing, learning, memory, and communication. This complexity, combined with the need for precise regulation of gene expression, may lead to a higher incidence of alternative splicing events in the brain compared to other tissues.