Divergence of exonic splicing elements after gene duplication and the impact on gene structures (original) (raw)
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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 (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.
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 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 ...
Molecular Cell, 2006
Exonic splicing regulatory sequences (ESRs) are cisacting factor binding sites that regulate constitutive and alternative splicing. A computational method based on the conservation level of wobble positions and the overabundance of sequence motifs between 46,103 human and mouse orthologous exons was developed, identifying 285 putative ESRs. Alternatively spliced exons that are either short in length or contain weak splice sites show the highest conservation level of those ESRs, especially toward the edges of exons. ESRs that are abundant in those subgroups show a different distribution between constitutively and alternatively spliced exons. Representatives of these ESRs and two SR protein binding sites were shown, experimentally, to display variable regulatory effects on alternative splicing, depending on their relative locations in the exon. This finding signifies the delicate positional effect of ESRs on alternative splicing regulation.
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.
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).
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.
Listening to Silence and Understanding Nonsense: Exonic Mutations That Affect Splicing
Nature Reviews Genetics, 2002
A typical mammalian gene is composed of several relatively short exons that are interrupted by much longer introns. To generate correct, mature mRNAs, the exons must be identified and joined together precisely and efficiently, in a process that requires the coordinated action of five small nuclear (sn)RNAs (U1, U2 and U4-U6) and more than 60 polypeptides 1,2 . The inaccurate recognition of exon-intron boundaries or the failure to remove an intron generates aberrant mRNAs that are either unstable or code for defective or deleterious protein isoforms.