Alternative Splicing and Genome Evolution


The alternative splicing of pre‐messenger ribonucleic acids is an important mechanism of proteomic diversity and plays a significant role in determining a protein's structure, function and localisation. Because of its ubiquity as a mechanism (affecting most human genes) and its broad functional role (in development and physiology), it is expected to make an important contribution to the evolution of trait complexity. Here, we consider the evolutionary consequences of this key cellular mechanism, which are being uncovered by important developments in genomic technology and methodology.

Key Concepts

  • Alternative splicing is a key cellular process driving phenotypic diversity and functional innovation.
  • Gene duplication and other molecular processes can interact with alternative splicing in highly complex ways to drive genome evolution.
  • Gene regulation, including alternative splicing, is thought to account for the extraordinary divergence in traits between closely related species given the small degree of molecular divergence between orthologous protein sequences.
  • Nonsense‐mediated decay (with its conserved machinery and targets across large evolutionary time spans) can act as a quality control mechanism on alternative splicing to guard the cell against potentially deleterious gene products.
  • In studies of the evolutionary landscape of alternative splicing (in multiple tissues across hundreds of millions of years of evolutionary time span), the identity of the species is the primary source of the variability in overall alternative splicing patterns, whereas tissue type is the main source for overall gene expression patterns.

Keywords: alternative splicing; genome; evolution; transcriptome; proteome; complexity; gene duplication; nonsense‐mediated decay; splicing regulatory elements; neo‐functionalisation; sub‐functionalisation

Figure 1. (a) Alternative splicing and other molecular processes may interact in complex ways to drive the evolution of trait complexity. Three (hypothetical) species‐specific transcript isoforms (SF1, SF2 and SF3) are shown. The structure of the splice form (i.e. exon skipping) is regulated by the presence of editing sites. Boxes represent exons, whereas lines represent introns. The stars in the splice form SF1 show the location of the RNA editing sites. (b) Alternative splicing can influence trait complexity through the regulatory circuity of the cell. Shown here is a cis‐acting splicing regulatory element (an ISE) that regulates the skipping of an adjacent exon. The arrow indicates a variable site within the ISE. The domain affected by the exon skipping can result in a dramatic change in protein function.


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Further Reading

Bradley RK, et al. (2012) Alternative splicing of RNA triplets is often regulated and accelerates proteome evolution. PLoS Biology 10: e1001229, doi:10.1371/journal.pbio.1001229.

Gamazon ER and Stranger BE (2014) Genomics of alternative splicing: evolution, development and pathophysiology. Human Genetics 133: 679–687. DOI: 10.1007/s00439‐013‐1411‐3.

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Gamazon, Eric R(Jan 2016) Alternative Splicing and Genome Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026311]