ArticleProceedings of the National Academy of Sciences of the United States of America2005
Evidence of functional selection pressure for alternative splicing events that accelerate evolution of protein subsequences.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 134 citations in OpenAlex.
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- Expression of Truncated Products at the 5'-Terminal Region of RIPK2 and Evolutive Aspects that Support Their Biological Importance.Genome biology and evolution · 2024Article
- Nucleotide-level distance metrics to quantify alternative splicing implemented in TranD.Nucleic acids research · 2024Article
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- A serpin gene from a parasitoid wasp disrupts host immunity and exhibits adaptive alternative splicing.PLoS pathogens · 2023Article
- A Practical Guide to Design and Assess a Phylogenomic Study.Genome biology and evolution · 2022Article
- Evolutionary patterns of nucleotide substitution rates in plastid genomes ofEcology and evolution · 2021Article
- Alu insertion variants alter mRNA splicing.Nucleic acids research · 2019Article
- Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high-throughput mutagenesis.Nature communications · 2018Article
- Abundance of clinical variants in exons included in multiple transcripts.Human genomics · 2018Article
- Adenine Enrichment at the Fourth CDS Residue in Bacterial Genes Is Consistent with Error Proofing for +1 Frameshifts.Molecular biology and evolution · 2017Article
- Depletion of somatic mutations in splicing-associated sequences in cancer genomes.Genome biology · 2017Article
- Article
- Estimating the prevalence of functional exonic splice regulatory information.Human genetics · 2017Review
- Correspondence of D. melanogaster and C. elegans developmental stages revealed by alternative splicing characteristics of conserved exons.BMC genomics · 2017Article
- Type III polyketide synthase repertoire in Zingiberaceae: computational insights into the sequence, structure and evolution.Development genes and evolution · 2016Article
- Comparative genomics of grass EST libraries reveals previously uncharacterized splicing events in crop plants.BMC plant biology · 2015Article
- Article
- Identification, characterization, and utilization of single copy genes in 29 angiosperm genomes.BMC genomics · 2014Article
- Genomics of alternative splicing: evolution, development and pathophysiology.Human genetics · 2014Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Recently, it was proposed that alternative splicing may act as a mechanism for opening accelerated paths of evolution, by reducing negative selection pressure, but there has been little evidence so far that this mechanism could produce adaptive benefit. Here, we use metrics of very different types of selection pressures [e.g., against amino acid mutations (Ka/Ks), against mutations at synonymous sites (Ks), and for protein reading-frame preservation] to address this question by genomewide analyses of human, chimpanzee, mouse, and rat. These data show that alternative splicing relaxes Ka/Ks selection pressure up to 7-fold, but intriguingly this effect is accompanied by a strong increase in selection pressure against synonymous mutations, which propagates into the adjacent intron, and correlates strongly with the alternative splicing level observed for each exon. These effects are highly local to the alternatively spliced exon. Comparisons of these four genomes consistently show an increase in the density of amino acid mutations (Ka) in alternatively spliced exons and a decrease in the density of synonymous mutations (Ks). This selection pressure against synonymous mutations in alternatively spliced exons was accompanied in all four genomes by a striking increase in selection pressure for protein reading-frame preservation, and both increased markedly with increasing evolutionary age. Restricting our analysis to a subset of exons with strong evidence for biologically functional alternative splicing produced identical results. Thus alternative splicing apparently can create evolutionary "hotspots" within a protein sequence, and these events have evidently been selected for during mammalian evolution.
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