Whence genes in pieces: reconstruction of the exon–intron gene structures of the last eukaryotic common ancestor and other ancestral eukaryotes

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Eugene V. Koonin, Miklos Csuros, Igor B. Rogozin

Published Online: Nov 08 2012

DOI: 10.1002/wrna.1143

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Abstract In eukaryotes, protein‐coding sequences are interrupted by non‐coding sequences known as introns. During mRNA maturation, introns are excised by the spliceosome and the coding regions, exons, are spliced to form the mature coding region. The intron densities widely differ between eukaryotic lineages, from 6 to 7 introns per kb of coding sequence in vertebrates, some invertebrates and green plants, to only a few introns across the entire genome in many unicellular eukaryotes. Evolutionary reconstructions using maximum likelihood methods suggest intron‐rich ancestors for each major group of eukaryotes. For the last common ancestor of animals, the highest intron density of all extant and extinct eukaryotes was inferred, at 120–130% of the human intron density. Furthermore, an intron density within 53–74% of the human values was inferred for the last eukaryotic common ancestor. Accordingly, evolution of eukaryotic genes in all lines of descent involved primarily intron loss, with substantial gain only at the bases of several branches including plants and animals. These conclusions have substantial biological implications indicating that the common ancestor of all modern eukaryotes was a complex organism with a gene architecture resembling those in multicellular organisms. Alternative splicing most likely initially appeared as an inevitable result of splicing errors and only later was employed to generate structural and functional diversification of proteins. WIREs RNA 2013, 4:93–105. doi: 10.1002/wrna.1143 This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution

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Reconstruction of intron gains and losses in the evolution of eukaryotes and intron density in ancestral eukaryote forms. Branch widths are proportional to intron density which is shown next to terminal taxa and some deep ancestors, in units of the introns count per 1 kb coding sequence. Human (Hsap) is marked by a blue dot. The inset shows the likelihood distribution (blue) and the 95% confidence interval (red bar, with the median value indicated by a circle) for the intron density of LECA using MCMC; the values obtained with ML and Dollo parsimony are indicated by arrows. Species names and abbreviations: Aureococcus anophagefferens (Aano), Aedes aegypti (Aaeg), Agaricusbisporus (Abis), Anopheles gambiae (Agam), Allomyces macrogynus (Amac), Apis mellifera (Amel), Aspergillus nidulans (Anid), Acyrthosiphon pisum (Apis), Arabidopsis thaliana (Atha), Babesia bovis (Bbov), Batrachochytrium dendrobatidis (Bden), Branchiostoma floridae (Bflo), Botryotinia fuckeliana (Bfuc), Brugia malayi (Bmal), Bombyx mori (Bmor), Coccomyxa sp. C‐169 (C169), Chlorella sp. NC64a (C64a), Caenorhabditis briggsae (Cbri), Caenorhabditis elegans (Cele), Coprinopsis cinerea okayama (Ccin), Cochliobolus heterostrophus C5 (Chet), Coccidioides immitis (Cimm), Ciona intestinalis (Cint), Cryptococcus neoformans var. neoformans (Cneo), Chlamydomonas reinhardtii (Crei), Capitella teleta (Ctel), Capsaspora owczarzaki (Cowc), Dictyostelium discoideum (Ddis), Dictyostelium purpureum (Dpur), Drosophila melanogaster (Dmel), Drosophila mojavenis (Dmoj), Daphnia pulex (Dpul), Danio rerio (Drer), Entamoeba dispar (Edis), Entamoeba histolytica (Ehis), Emiliania huxleyi (Ehux), Fragilariopsis cylindrus (Fcyl), Phanerochaete chrysosporium (Fchr), Phaeodactylum tricornutum (Ftri), Gallus gallus (Ggal), Gibberella zeae (Gzea), Hydra magnipapillata (Hmag), Helobdella robusta (Hrob), Homo sapiens (Hsap), Ixodes scapularis (Isca), Laccaria bicolor (Lbic), Lottia gigantea (Lgig), Micromonas sp. RCC299 (M299), Monosiga brevicollis (Mbre), Mucor circinelloides (Mcir), Mycosphaerella fijiensis (Mfij), Mycosphaerella graminicola (Mgra), Magnaporthe grisea (Mgri), Melampsora laricis‐populina (Mlar), Micromonas pusilla (Mpus), Neurospora crassa (Ncra), Nematostella vectensis (Nvec), Nasonia vitripennis (Nvit), Ostreococcus sp. RCC809 (O809), Ostreococcus lucimarinus (Oluc), Oryza sativa japonica (Osat), Ostreococcus taurii (Otau), Phytophthora capsici (Pcap), Plasmodium falciparum (Pfal), Puccinia graminis (Pgra), Pediculus humanus (Phum), Phaeosphaeria nodorum (Pnod), Physcomitrella patens subsp. patens (Ppat), Phytophthora ramorum (Pram), Pyrenophora tritici‐repentis (Prep), Proterospongia sp. (Prsp), Phytophthora sojae (Psoj), Paramecium tetraurelia (Ptet), Plasmodium vivax (Pviv), Plasmodium yoelii yoelii (Pyoe), Rhizopus oryzae (Rory), Sorghum bicolor (Sbic), Saccharomyces cerevisiae (Scer), Schizosaccharomyces japonicus (Sjap), Schistosoma mansoni (Sman), Selaginella moellendorffii (Smoe), Schizosaccharomyces pombe (Spom), Spizellomyces punctatus (Spun), Strongylocentrotus purpuratus (Spur), Sporobolomyces roseus (Sros), Sclerotinia sclerotiorum (Sscl), Trichoplax adhaerens (Tadh), Theileria annulata (Tann), Tribolium castaneum (Tcas), Toxoplasma gondii (Tgon), Taenopygia guttata (Tgut), Theileria parvum (Tpar), Thalassiosira pseudonana (Tpse), Tetrahymena thermophila (Tthe), Ustilago maydis (Umay), Uncinocarpus reesii (Uree), Volvox carteri (Vcar), Vitis vinifera (Vvin). (Modified from Ref 36 under Creative Commons CC0 public domain dedication; The Public Library of Science, 2011)

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Distributions of intron density in genes of diverse eukaryotes. (a) Intron density versus intron length. (b) Number of introns versus number of genes in eukaryotes. The y = d ∗︁ x lines show per gene intron density (d = 0.06…8.8). The maximum intron density (∼8.8 introns/gene) is in Ciona intestinalis. Circles on the axes are projections of the data points that serve to show the distributions of the respective quantities. The data is from Ref 36 with 17 additional species. Species names and abbreviations: Anolis carolinensis (Acar), Aureococcus anophagefferens (Aano), Aedes aegypti (Aaeg), Agaricusbisporus (Abis), Anopheles gambiae (Agam), Allomyces macrogynus (Amac), Apis mellifera (Amel), Aspergillus nidulans (Anid), Acyrthosiphon pisum (Apis), Arabidopsis thaliana (Atha), Babesia bovis (Bbov), Batrachochytrium dendrobatidis (Bden), Branchiostoma floridae (Bflo), Botryotinia fuckeliana (Bfuc), Brugia malayi (Bmal), Bombyx mori (Bmor), Bigelowiella natans (Bnat), Coccomyxa sp. C‐169 (C169), Chlorella sp. NC64a (C64a), Caenorhabditis briggsae (Cbri), Caenorhabditis elegans (Cele), Coprinopsis cinerea okayama (Ccin), Cochliobolus heterostrophus C5 (Chet), Coccidioides immitis (Cimm), Ciona intestinalis (Cint), Cryptococcus neoformans var. neoformans (Cneo), Chlamydomonas reinhardtii (Crei), Capitella teleta (Ctel), Capsaspora owczarzaki (Cowc), Cucumis sativus (Cucu), Dictyostelium discoideum (Ddis), Dictyostelium purpureum (Dpur), Drosophila melanogaster (Dmel), Drosophila mojavenis (Dmoj), Daphnia pulex (Dpul), Danio rerio (Drer), Entamoeba dispar (Edis), Entamoeba histolytica (Ehis), Emiliania huxleyi (Ehux), Fragilariopsis cylindrus (Fcyl), Phanerochaete chrysosporium (Fchr), Phaeodactylum tricornutum (iFtri), Gallus gallus (Ggal), Gibberella zeae (Gzea), Hydra magnipapillata (Hmag), Helobdella robusta (Hrob), Homo sapiens (Hsap), Ixodes scapularis (Isca), Laccaria bicolor (Lbic), Loa loa (Lloa), Lottia gigantea (Lgig), Manihot esculenta (Mesc), Micromonas sp. RCC299 (M299), Monosiga brevicollis (Mbre), Mucor circinelloides (Mcir), Mycosphaerella fijiensis (Mfij), Mycosphaerella graminicola (Mgra), Magnaporthe grisea (Mgri), Melampsora laricis‐populina (Mlar), Micromonas pusilla (Mpus), Neurospora crassa (Ncra), Nematostella vectensis (Nvec), Nasonia vitripennis (Nvit), Ostreococcus sp. RCC809 (O809), Ostreococcus lucimarinus (Oluc), Oryza sativa japonica (Osat), Ostreococcus taurii (Otau), Phytophthora capsici (Pcap), Plasmodium falciparum (Pfal), Puccinia graminis (Pgra), Pediculus humanus (Phum), Perkinsus marinus (Pmar), Phaeosphaeria nodorum (Pnod), Physcomitrella patens subsp. patens (Ppat), Phytophthora ramorum (Pram), Pyrenophora tritici‐repentis (Prep), Proterospongia sp. (Prsp), Phytophthora sojae (Psoj), Paramecium tetraurelia (Ptet), Plasmodium vivax (Pviv), Plasmodium yoelii yoelii (Pyoe), Pseudo‐nitzschia multiseries (Pnit), Punctularia strigosozonata (Pstr), Rhizopus oryzae (Rory), Saprolegnia parasitica (Spar), Setosphaeria turcica (Stur), Sorghum bicolor (Sbic), Saccharomyces cerevisiae (Scer), Schizosaccharomyces japonicus (Sjap), Schistosoma mansoni (Sman), Selaginella moellendorffii (Smoe), Schizosaccharomyces pombe (Spom), Spizellomyces punctatus (Spun), Sphaeroforma arctica (Sarc), Strongylocentrotus purpuratus (Spur), Sporobolomyces roseus (Sros), Sclerotinia sclerotiorum (Sscl), Trichoplax adhaerens (Tadh), Theileria annulata (Tann), Tribolium castaneum (Tcas), Toxoplasma gondii (Tgon), Taenopygia guttata (Tgut), Thecamonas trahens (Ttra), Theileria parvum (Tpar), Thalassiosira pseudonana (Tpse), Tetrahymena thermophila (Tthe), Thielavia terrestris (Tter), Trametes versicolor (Tver), Ustilago maydis (Umay), Uncinocarpus reesii (Uree), Volvox carteri (Vcar), Vitis vinifera (Vvin), Wolfiporia cocos (Wcoc), Wuchereria bancrofti (Wban), Xanthoria parietina (Xpar).

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A hypothetical scenario of the earliest stages in the evolution of eukaryote gene structure. The scheme shows the inferred sequence of events from putative ancestors of eukaryotes to the origin of spliceosomal introns from Group II introns invading the host genome upon mitochondrial endosymbiosis.12

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