Intron Evolution: Testing Hypotheses of Intron Evolution Using the Phylogenomics of Tetraspanins

Antonio Garcia-España,Tung-Tien Sun,Rob Desalle,Roso Mares,Juan Valcarcel

doi:10.1371/journal.pone.0004680

Antonio Garcia-España, Tung-Tien Sun + Show 3 more

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https://doi.org/10.1371/journal.pone.0004680

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Abstract

BackgroundAlthough large scale informatics studies on introns can be useful in making broad inferences concerning patterns of intron gain and loss, more specific questions about intron evolution at a finer scale can be addressed using a gene family where structure and function are well known. Genome wide surveys of tetraspanins from a broad array of organisms with fully sequenced genomes are an excellent means to understand specifics of intron evolution. Our approach incorporated several new fully sequenced genomes that cover the major lineages of the animal kingdom as well as plants, protists and fungi. The analysis of exon/intron gene structure in such an evolutionary broad set of genomes allowed us to identify ancestral intron structure in tetraspanins throughout the eukaryotic tree of life.Methodology/Principal FindingsWe performed a phylogenomic analysis of the intron/exon structure of the tetraspanin protein family. In addition, to the already characterized tetraspanin introns numbered 1 through 6 found in animals, three additional ancient, phase 0 introns we call 4a, 4b and 4c were found. These three novel introns in combination with the ancestral introns 1 to 6, define three basic tetraspanin gene structures which have been conserved throughout the animal kingdom. Our phylogenomic approach also allows the estimation of the time at which the introns of the 33 human tetraspanin paralogs appeared, which in many cases coincides with the concomitant acquisition of new introns. On the other hand, we observed that new introns (introns other than 1–6, 4a, b and c) were not randomly inserted into the tetraspanin gene structure. The region of tetraspanin genes corresponding to the small extracellular loop (SEL) accounts for only 10.5% of the total sequence length but had 46% of the new animal intron insertions.Conclusions/SignificanceOur results indicate that tests of intron evolution are strengthened by the phylogenomic approach with specific gene families like tetraspanins. These tests add to our understanding of genomic innovation coupled to major evolutionary divergence events, functional constraints and the timing of the appearance of evolutionary novelty.

Highlights

Eukaryotic protein coding genes are interspersed with non coding sequences called introns that are removed from the corresponding transcripts by the spliceosome, a complex RNAprotein assemblage
Taking a phylogenomic approach to understand the distribution of intron/exon evolution in a suitable gene family would allow the determination of ancestral states of intron presence/absence, and allow for the correlation of intron loss/ gain events with function and to place time estimates on intron/ exon evolutionary events
In addition to the six reported ancestral introns, 1 to 6, we identified three new ancient introns we call 4a, 4b, and 4c, which are conserved from the ancestors of the non bilaterian animal, Placozoa (Trichoplax adherens, introns 4b and 4c) and the unicellular choanoflagellate (Monosiga; intron 4a) to mammals (Fig. 2, Figures S1, S2 and S3)

Summary

Introduction

Eukaryotic protein coding genes are interspersed with non coding sequences called introns that are removed from the corresponding transcripts by the spliceosome, a complex RNAprotein assemblage. Despite the vast amount of information generated since their discovery and the importance of introns in understanding gene organization, many issues regarding intron evolution remain enigmatic These issues include the timing of intron origin and proliferation, the evolutionary history of introns and mechanisms of intron loss/gain in eukaryotic organisms, and the evolutionary dynamics that can explain their existence. The recently fully sequenced genomes of multiple eukaryotic species covering broad evolutionary divergences, makes analysis of intronexon structure of individual gene families an interesting option. Large scale informatics studies on introns can be useful in making broad inferences concerning patterns of intron gain and loss, more specific questions about intron evolution at a finer scale can be addressed using a gene family where structure and function are well known. The analysis of exon/intron gene structure in such an evolutionary broad set of genomes allowed us to identify ancestral intron structure in tetraspanins throughout the eukaryotic tree of life

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Conclusion