Divergence of exonic splicing elements after gene duplication and the impact on gene structures (original) (raw)
Alternative splicing and evolution: diversification, exon definition and function
Nature Reviews Genetics, 2010
Over the past decade, it has been shown that alternative splicing (AS) is a major mechanism for the enhancement of transcriptome and proteome diversity, particularly in mammals. Splicing can be found in species from bacteria to humans, but its prevalence and characteristics vary considerably. Evolutionary studies are helping to address questions that are fundamental to understanding this important process: how and when did AS evolve? Which AS events are functional? What are the evolutionary forces that shaped, and continue to shape, AS? And what determines whether an exon is spliced in a constitutive or alternative manner? In this Review, we summarize the current knowledge of AS and evolution and provide insights into some of these unresolved questions.
The evolutionary relationship between gene duplication and alternative splicing
Gene, 2008
Gene duplication and alternative splicing (AS) are the two major evolutionary mechanisms that can bring the functional variation by increasing gene diversification. The purpose of this research is to understand the evolutionary relationship between these two different mechanisms, utilizing available data resources. We found the proportion of AS loci and the average number of AS isoforms per locus to be larger in duplicated genes compared to those in singleton genes. However we also found that small gene families have larger proportion of AS loci and larger average number of AS isoforms per locus than large gene families. These results suggest that gene duplication allows for more alternative splicing events to occur on newly duplicated copies than on singletons, probably due to the reduced functional constraint on the duplicates. Smaller average number of AS isoforms in the larger gene families can be explained by the decreased possibility for new useful function to be created via a new alternative splicing event.
The (In)dependence of Alternative Splicing and Gene Duplication
PLOS Computational Biology, 2007
Alternative splicing (AS) and gene duplication (GD) both are processes that diversify the protein repertoire. Recent examples have shown that sequence changes introduced by AS may be comparable to those introduced by GD. In addition, the two processes are inversely correlated at the genomic scale: large gene families are depleted in splice variants and vice versa. All together, these data strongly suggest that both phenomena result in interchangeability between their effects. Here, we tested the extent to which this applies with respect to various protein characteristics. The amounts of AS and GD per gene are anticorrelated even when accounting for different gene functions or degrees of sequence divergence. In contrast, the two processes appear to be independent in their influence on variation in mRNA expression. Further, we conducted a detailed comparison of the effect of sequence changes in both alternative splice variants and gene duplicates on protein structure, in particular the size, location, and types of sequence substitutions and insertions/deletions. We find that, in general, alternative splicing affects protein sequence and structure in a more drastic way than gene duplication and subsequent divergence. Our results reveal an interesting paradox between the anticorrelation of AS and GD at the genomic level, and their impact at the protein level, which shows little or no equivalence in terms of effects on protein sequence, structure, and function. We discuss possible explanations that relate to the order of appearance of AS and GD in a gene family, and to the selection pressure imposed by the environment. Citation: Talavera D, Vogel C, Orozco M, Teichmann SA, de la Cruz X (2007) The (in)dependence of alternative splicing and gene duplication. PLoS Comput Biol 3(3): e33.
Alternative splicing and evolution
BioEssays, 2003
Alternative splicing is a critical post‐transcriptional event leading to an increase in the transcriptome diversity. Recent bioinformatics studies revealed a high frequency of alternative splicing. Although the extent of AS conservation among mammals is still being discussed, it has been argued that major forms of alternatively spliced transcripts are much better conserved than minor forms.1 It suggests that alternative splicing plays a major role in genome evolution allowing new exons to evolve with less constraint. BioEssays 25:1031–1034, 2003. © 2003 Wiley Periodicals, Inc.
BMC Evolutionary Biology, 2007
Background: Alternative splicing has been reported in various eukaryotic groups including plants, apicomplexans, diatoms, amoebae, animals and fungi. However, whether widespread alternative splicing has evolved independently in the different eukaryotic groups or was inherited from their last common ancestor, and may therefore predate multicellularity, is still unknown. To better understand the origin and evolution of alternative splicing and its usage in diverse organisms, we studied alternative splicing in 12 eukaryotic species, comparing rates of alternative splicing across genes of different functional classes, cellular locations, intron/exon structures and evolutionary origins.
The evolutionary fate of alternatively spliced homologous exons after gene duplication
Genome biology and evolution, 2015
Alternative splicing and gene duplication are the two main processes responsible for expanding protein functional diversity. While gene duplication can generate new genes and alternative splicing can introduce variation via alternative gene products. the interplay between the two processes is complex and poorly understood. Here we have carried out a study of the evolution of alternatively spliced exons after gene duplication to better understand the interaction between the two processes. We created a manually curated set of 97 human genes with mutually exclusively spliced homologous exons and analysed the evolution of these exons across five distantly related vertebrates (lamprey, spotted gar, zebrafish, fugu, and coelacanth). Most of these exons had an ancient origin (more than 400 Mya). There are two extreme evolutionary fates for homologous exons after gene duplication and we found examples supporting both. We observed 11 cases in which gene duplication was accompanied by splice ...
Alternative splicing: current perspectives
Alternative splicing is a well-characterized mechanism by which multiple transcripts are generated from a single mRNA precursor. By allowing production of several protein isoforms from one pre-mRNA, alternative splicing contributes to proteomic diversity. But what do we know about the origin of this mechanism? Do the same evolutionary forces apply to alternatively and constitutively splice exons? Do similar forces act on all types of alternative splicing? Are the products generated by alternative splicing functional? Why is ''improper'' recognition of exons and introns allowed by the splicing machinery? In this review, we summarize the current knowledge regarding these issues from an evolutionary perspective.
Alternative splicing and protein structure evolution
Nucleic Acids Research, 2007
Alternative splicing is thought to be one of the major sources for functional diversity in higher eukaryotes. Interestingly, when mapping splicing events onto protein structures, about half of the events affect structured and even highly conserved regions i.e. are non-trivial on the structure level. This has led to the controversial hypothesis that such splice variants result in nonsense-mediated mRNA decay or non-functional, unstructured proteins, which do not contribute to the functional diversity of an organism. Here we show in a comprehensive study on alternative splicing that proteins appear to be much more tolerant to structural deletions, insertions and replacements than previously thought. We find literature evidence that such nontrivial splicing isoforms exhibit different functional properties compared to their native counterparts and allow for interesting regulatory patterns on the protein network level. We provide examples that splicing events may represent transitions between different folds in the protein sequence-structure space and explain these links by a common genetic mechanism. Taken together, those findings hint to a more prominent role of splicing in protein structure evolution and to a different view of phenotypic plasticity of protein structures.
Conserved and species-specific alternative splicing in mammalian genomes
BMC Evolutionary Biology, 2007
Background: Alternative splicing has been shown to be one of the major evolutionary mechanisms for protein diversification and proteome expansion, since a considerable fraction of alternative splicing events appears to be species-or lineage-specific. However, most studies were restricted to the analysis of cassette exons in pairs of genomes and did not analyze functionality of the alternative variants.
Genomics of alternative splicing: evolution, development and pathophysiology
Human Genetics, 2014
that the organization of genes in higher organisms involves expressed regions (exons) that are interrupted by introns ["'silent' DNa", as walter Gilbert described these sequences (Gilbert 1978) over 3 decades ago] to be absent from the mature messenger RNa has, as Francis Crick pointed out (Crick 1979) with great foresight, been the source of "an extraordinary fascination for almost everybody concerned with the problem" of the origin of alternative splicing. a related complex question to that of origin concerns the adaptive significance of alternative splicing (Xing and Lee 2005; Modrek and Lee 2003).