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At least 235 records · Page 13Linked to original sources
PubMed2005

mRNA-mediated intron losses: evidence from extraordinarily large exons.

Multicellular eukaryotes that have high intron density have their introns almost evenly distributed within genes, but unicellular eukaryotes that are generally intron poor have their introns asymmetrically distributed toward the 5' ends of genes. This was explained by homologous recombination of genomic DNA with the cDNA reverse transcribed from the 3' polyadenylated tail of spliced mRNA. This paper is to study whether mRNA-mediated intron losses have ever occurred in multicellular eukaryotes. If intron losses were mRNA-mediated, adjacent introns should be commonly lost together. A direct result is fusion of several previously adjacent exons and producing a large exon. We found that extraordinarily large exons (ELEs) are common not only in unicellular eukaryotes but also in multicellular eukaryotes. The percentage of genes having ELEs is negatively correlated with intron abundance. In addition, the number of lost introns estimated from the relative lengths of ELEs is negatively correlated with the number of extant introns. These results support mRNA-mediated intron losses in all eukaryotes. Moreover, we found that the ELEs of intron-common eukaryotes (with more than 0.5 intron per gene on average) are not only located at 3' ends but also at 5' ends and the middle of genes. This is contrary to what would be expected if the involved cDNAs were reverse transcribed from the 3' polyadenosine ends. A remarkable difference in intron distribution was revealed between intron-rare eukaryotes and intron-common eukaryotes. The intron-rare eukaryotes show very strong 5'-biased intron distribution, whereas the intron-common eukaryotes display even intron distribution or only weak 5'-biased distribution. We suspected that intron losses from 3' end of genes may be limited in intron-rare eukaryotes. The intron losses from intron-common eukaryotes should have other priming mechanism, like self-primed reverse transcription.

Animals↗
PubMed1995

Evidence for the late origin of introns in chloroplast genes from an evolutionary analysis of the genus Euglena.

The origin of present day introns is a subject of spirited debate. Any intron evolution theory must account for not only nuclear spliceosomal introns but also their antecedents. The evolution of group II introns is fundamental to this debate, since group II introns are the proposed progenitors of nuclear spliceosomal introns and are found in ancient genes from modern organisms. We have studied the evolution of chloroplast introns and twintrons (introns within introns) in the genus Euglena. Our hypothesis is that Euglena chloroplast introns arose late in the evolution of this lineage and that twintrons were formed by the insertion of one or more introns into existing introns. In the present study we find that 22 out of 26 introns surveyed in six different photosynthesis-related genes from the plastid DNA of Euglena gracilis are not present in one or more basally branching Euglena spp. These results are supportive of a late origin for Euglena chloroplast group II introns. The psbT gene in Euglena viridis, a basally branching Euglena species, contains a single intron in the identical position to a psbT twintron from E.gracilis, a derived species. The E.viridis intron, when compared with 99 other Euglena group II introns, is most similar to the external intron of the E.gracilis psbT twintron. Based on these data, the addition of introns to the ancestral psbT intron in the common ancester of E.viridis and E.gracilis gave rise to the psbT twintron in E.gracilis.

Animals↗
PubMed2001

A structural and phylogenetic analysis of the group IC1 introns in the order Bangiales (Rhodophyta).

Our previous study of the North American biogeography of Bangia revealed the presence of two introns inserted at positions 516 and 1506 in the nuclear-encoded SSU rRNA gene. We subsequently sequenced nuclear SSU rRNA in additional representatives of this genus and the sister genus Porphyra in order to examine the distribution, phylogeny, and structural characteristics of these group I introns. The lengths of these introns varied considerably, ranging from 467 to 997 nt for intron 516 and from 509 to 1,082 nt for intron 1506. The larger introns contained large insertions in the P2 domain of intron 516 and the P1 domain of intron 1506 that correspond to open reading frames (ORFs) with His-Cys box homing endonuclease motifs. These ORFs were found on the complementary strand of the 1506 intron in Porphyra fucicola and P. umbilicalis (HG), unlike the 516 intron in P. abbottae, P. kanakaensis, P. tenera (SK), Bangia fuscopurpurea (Helgoland), and B. fuscopurpurea (MA). Frameshifts were noted in the ORFs of the 516 introns in P. kanakaensis and B. fuscopurpurea (HL), and all ORFs terminated prematurely relative to the amino acid sequence for the homing endonuclease I-Ppo I. This raises the possibility that these sequences are pseudogenes. Phylogenies generated using sequences of both introns and the 18S rRNA gene were congruent, which indicated long-term immobility and vertical inheritance of the introns followed by subsequent loss in more derived lineages. The introns within the florideophyte species Hildenbrandia rubra (position 1506) were included to determine relationships with those in the Bangiales. The two sequences of intron 1506 analyzed in Hildenbrandia were positioned on a well-supported branch associated with members of the Bangiales, indicating possible common ancestry. Structural analysis of the intron sequences revealed a signature structural feature in the P5b domain of intron 516 that is unique to all Bangialean introns in this position and not seen in intron 1506 or other group IC1 introns.

Amino Acid Sequence↗
PubMed1996

Evolutionary history of introns in a multidomain globin gene.

The Artemia hemoglobin contains two subunits that are similar or different chains of nine globin domains. The domains are ancestrally related and are presumed to be derived from copies of an original single-domain parent gene. Since the gene copies have remained in the same environment for several hundred million years they provide an excellent model for the investigation of intron stability. The cDNA for one of the two types of nine-domain subunit (domains T1-T9) has been sequenced. Comparison with the corresponding genomic DNA reveals a total of 17 intradomain introns. Fourteen of the introns are in locations on the protein that are conventional in globins of other species. In eight of the nine domains an intron corresponds to the B helix, amino acid B12, following the second nucleotide (phase 2), and in six domains a G-helix intron is located between G6 and G7 (phase 0). The consistency of this pattern is supportive of the introns having been inherited from a single-domain parent gene. The remaining three introns are in unconventional locations. Two occur in the F helix, either in amino acid F3 (phase 1) in domain T3, or between F2 and F3 (phase 0) in domain T6. The two F introns strengthen an interpretation of intron inheritance since globin F introns are rare, and in domains T3 and T6 they replace rather than supplement the conventional G introns, as though displacement from G to F occurred before that part of the gene became duplicated. It is inferred that one of the F introns subsequently moved by one nucleotide. Similarly, the third unconventional intron location is the G intron in domain T4 which is in G6, phase 2, one nucleotide earlier than the other G introns. Domain T4 is also unusual in lacking a B intron. The pattern of introns in the Artemia globin gene supports a concept of general positional stability but the exceptions, where introns have moved out of reading frame, or have moved by several codons, or have been deleted, suggest that intron displacements can occur after inheritance from an ancient source.

Amino Acid Sequence↗
PubMed1997

Origin and inheritance of group I introns in 26S rRNA genes of Gaeumannomyces graminis.

Studies of the distribution of the three group I introns (intron A, intron T, and intron AT) in the 26S rDNA of Gaeumannomyces graminis had suggested that they were transferred to a common ancestor of G. graminis var. avenae and var. tritici after it had branched off from var. graminis. Intron AT and intron A exhibited vertical inheritance and coevolved in concert with their hosts. Intron loss could occur after its acquisition. Loss of any one of the three introns could occur in var. tritici whereas only loss of intron T had been found in the majority of var. avenae isolates. The existence of isolates of var. tritici and var. avenae with three introns suggested that intron loss could be reversed by intron acquisition and that the whole process is a dynamic one. This process of intron acquisition and intron loss reached different equilibrium points for different varieties and subgroups, which explained the irregular distribution of these introns in G. graminis. Each of the three group I introns was more closely related to other intron sequences that share the same insertion point in the 26S rDNA than to each other. These introns in distantly related organisms appeared to have a common ancestry. This system had provided a good model for studies on both the lateral transfer and common ancestry of group I introns in the 26S rRNA genes.

Ascomycota↗
PubMed2003

Selective constraints on intron evolution in Drosophila.

Intron sizes show an asymmetrical distribution in a number of organisms, with a large number of "short" introns clustered around a minimal intron length and a much broader distribution of longer introns. In Drosophila melanogaster, the short intron class is centered around 61 bp. The narrow length distribution suggests that natural selection may play a role in maintaining intron size. A comparison of 15 orthologous introns among species of the D. melanogaster subgroup indicates that, in general, short introns are not under greater DNA sequence or length constraints than long introns. There is a bias toward deletions in all introns (deletion/insertion ratio is 1.66), and the vast majority of indels are of short length (<10 bp). Indels occurring on the internal branches of the phylogenetic tree are significantly longer than those occurring on the terminal branches. These results are consistent with a compensatory model of intron length evolution in which slightly deleterious short deletions are frequently fixed within species by genetic drift, and relatively rare larger insertions that restore intron length are fixed by positive selection. A comparison of paralogous introns shared among duplicated genes suggests that length constraints differ between introns within the same gene. The janusA, janusB, and ocnus genes share two short introns derived from a common ancestor. The first of these introns shows significantly fewer indels than the second intron, although the two introns show a comparable number of substitutions. This indicates that intron-specific selective constraints have been maintained following gene duplication, which preceded the divergence of the D. melanogaster species subgroup.

Animals↗
PubMed2006

Intron size, abundance, and distribution within untranslated regions of genes.

Most research concerning the evolution of introns has largely considered introns within coding sequences (CDSs), without regard for introns located within untranslated regions (UTRs) of genes. Here, we directly determined intron size, abundance, and distribution in UTRs of genes using full-length cDNA libraries and complete genome sequences for four species, Arabidopsis thaliana, Drosophila melanogaster, human, and mouse. Overall intron occupancy (introns/exon kbp) is lower in 5' UTRs than CDSs, but intron density (intron occupancy in regions containing introns) tends to be higher in 5' UTRs than in CDSs. Introns in 5' UTRs are roughly twice as large as introns in CDSs, and there is a sharp drop in intron size at the 5' UTR-CDS boundary. We propose a mechanistic explanation for the existence of selection for larger intron size in 5' UTRs, and outline several implications of this hypothesis. We found introns to be randomly distributed within 5' UTRs, so long as a minimum required exon size was assumed. Introns in 3' UTRs were much less abundant than in 5' UTRs. Though this was expected for human and mouse that have intron-dependent nonsense-mediated decay (NMD) pathways that discourage the presence of introns within the 3' UTR, it was also true for A. thaliana and D. melanogaster, which may lack intron-dependent NMD. Our findings have several implications for theories of intron evolution and genome evolution in general.

3' Untranslated Regions↗
PubMed2005

Patterns of intron sequence evolution in Drosophila are dependent upon length and GC content.

BACKGROUND: Introns comprise a large fraction of eukaryotic genomes, yet little is known about their functional significance. Regulatory elements have been mapped to some introns, though these are believed to account for only a small fraction of genome wide intronic DNA. No consistent patterns have emerged from studies that have investigated general levels of evolutionary constraint in introns. RESULTS: We examine the relationship between intron length and levels of evolutionary constraint by analyzing inter-specific divergence at 225 intron fragments in Drosophila melanogaster and Drosophila simulans, sampled from a broad distribution of intron lengths. We document a strongly negative correlation between intron length and divergence. Interestingly, we also find that divergence in introns is negatively correlated with GC content. This relationship does not account for the correlation between intron length and divergence, however, and may simply reflect local variation in mutational rates or biases. CONCLUSION: Short introns make up only a small fraction of total intronic DNA in the genome. Our finding that long introns evolve more slowly than average implies that, while the majority of introns in the Drosophila genome may experience little or no selective constraint, most intronic DNA in the genome is likely to be evolving under considerable constraint. Our results suggest that functional elements may be ubiquitous within longer introns and that these introns may have a more general role in regulating gene expression than previously appreciated. Our finding that GC content and divergence are negatively correlated in introns has important implications for the interpretation of the correlation between divergence and levels of codon bias observed in Drosophila.

Animals↗
PubMed2002

Conservation of the positions of metazoan introns from sponges to humans.

Sponges (phylum Porifera) are the phylogenetic oldest Metazoa still extant. They can be considered as reference animals (Urmetazoa) for the understanding of the evolutionary processes resulting in the creation of Metazoa in general and also for the metazoan gene organization in particular. In the marine sponge Suberites domuncula, genes encoding p38 and JNK kinases contain nine and twelve introns, respectively. Eight introns in both genes share the same positions and the identical phases. One p38 intron slipped for six bases and the JNK gene has three more introns. However, the sequences of the introns are not conserved and the introns in JNK gene are generally much longer. Introns interrupt most of the conserved kinase subdomains I-XI and are found in all three phases (0, 1 and 2). We analyzed in details p38 and JNK genes from human, Caenorhabditis elegans and Drosophila melanogaster and found in most genes introns at the positions identical to those in sponge genes. The exceptions are two p38 genes from D. melanogaster that have lost all introns in the coding sequence. The positions of 11 introns in each of four human p38 genes are fully conserved and ten introns occupy identical positions as the introns in sponge p38 or JNK genes. The same is true for nine, out of ten introns in the human JNK-1 gene. The introns in human p38 and JNK genes are on average more than ten times longer than corresponding introns in sponges. It was proposed that yeast HOG1-like kinases (from i.e. Saccharomyces cerevisiae and Emericella nidulans) and metazoan p38 and JNK kinases are orthologues. p38 and JNK genes were created after the split from fungi by the duplication and diversification of the HOG1-like progenitor gene. Our results further support the common origin of p38 and JNK genes and speak in favor of a very early time of duplication. The ancestral gene contained at least ten introns, which are still present at the very conserved positions in p38 and JNK genes of extant animals. Four of these introns are present at the same positions in the HOG-like gene in the fungus E. nidulans. The others probably entered the ancestral gene after the split of fungi, but before the duplication of the gene and before the creation of the common, urmetazoan progenitor of all multicellular animals. A second gene coding for an immune molecule is described, the allograft inflammatory factor, which likewise showed a highly conserved exon/intron structure in S. domuncula and in human. These data show that the intron/exon borders are highly conserved in genes from sponges to human.

Amino Acid Sequence↗
PubMed2005

Analysis of evolution of exon-intron structure of eukaryotic genes.

The availability of multiple, complete eukaryotic genome sequences allows one to address many fundamental evolutionary questions on genome scale. One such important, long-standing problem is evolution of exon-intron structure of eukaryotic genes. Analysis of orthologous genes from completely sequenced genomes revealed numerous shared intron positions in orthologous genes from animals and plants and even between animals, plants and protists. The data on shared and lineage-specific intron positions were used as the starting point for evolutionary reconstruction with parsimony and maximum-likelihood approaches. Parsimony methods produce reconstructions with intron-rich ancestors but also infer lineage-specific, in many cases, high levels of intron loss and gain. Different probabilistic models gave opposite results, apparently depending on model parameters and assumptions, from domination of intron loss, with extremely intron-rich ancestors, to dramatic excess of gains, to the point of denying any true conservation of intron positions among deep eukaryotic lineages. Development of models with adequate, realistic parameters and assumptions seems to be crucial for obtaining more definitive estimates of intron gain and loss in different eukaryotic lineages. Many shared intron positions were detected in ancestral eukaryotic paralogues which evolved by duplication prior to the divergence of extant eukaryotic lineages. These findings indicate that numerous introns were present in eukaryotic genes already at the earliest stages of evolution of eukaryotes and are compatible with the hypothesis that the original, catastrophic intron invasion accompanied the emergence of the eukaryotic cells. Comparison of various features of old and younger introns starts shedding light on probable mechanisms of intron insertion, indicating that propagation of old introns is unlikely to be a major mechanism for origin of new ones. The existence and structure of ancestral protosplice sites were addressed by examining the context of introns inserted within codons that encode amino acids conserved in all eukaryotes and, accordingly, are not subject to selection for splicing efficiency. It was shown that introns indeed predominantly insert into or are fixed in specific protosplice sites which have the consensus sequence (A/C)AG|Gt.

Animals↗
PubMed2004

The evolutionary gain of spliceosomal introns: sequence and phase preferences.

Theories regarding the evolution of spliceosomal introns differ in the extent to which the distribution of introns reflects either a formative role in the evolution of protein-coding genes or the adventitious gain of genetic elements. Here, systematic methods are used to assess the causes of the present-day distribution of introns in 10 families of eukaryotic protein-coding genes comprising 1,868 introns in 488 distinct alignment positions. The history of intron evolution inferred using a probabilistic model that allows ancestral inheritance of introns, gain of introns, and loss of introns reveals that the vast majority of introns in these eukaryotic gene families were not inherited from the most recent common ancestral genes, but were gained subsequently. Furthermore, among inferred events of intron gain that meet strict criteria of reliability, the distribution of sites of gain with respect to reading-frame phase shows a 5:3:2 ratio of phases 0, 1 and 2, respectively, and exhibits a nucleotide preference for MAG GT (positions -3 to +2 relative to the site of gain). The nucleotide preferences of intron gain may prove to be the ultimate cause for the phase bias. The phase bias of intron gain is sufficient to account quantitatively for the well-known 5:3:2 bias in phase frequencies among extant introns, a conclusion that holds even when taxonomic heterogeneity in phase patterns is considered. Thus, intron gain accounts for the vast majority of extant introns and for the bias toward phase 0 introns that previously was interpreted as evidence for ancient formative introns.

Animals↗