New Maximum Likelihood Estimators for Eukaryotic Intron Evolution

The evolution of spliceosomal introns remains poorly understood. Although many approaches have been used to infer intron evolution from the patterns of intron position conservation, the results to date have been contradictory. In this paper, we address the problem using a novel maximum likelihood method, which allows estimation of the frequency of intron insertion target sites, together with the rates of intron gain and loss. We analyzed the pattern of 10,044 introns (7,221 intron positions) in the conserved regions of 684 sets of orthologs from seven eukaryotes. We determined that there is an average of one target site per 11.86 base pairs (bp) (95% confidence interval, 9.27 to 14.39 bp). In addition, our results showed that: (i) overall intron gains are ~25% greater than intron losses, although specific patterns vary with time and lineage; (ii) parallel gains account for ~18.5% of shared intron positions; and (iii) reacquisition following loss accounts for ~0.5% of all intron positions. Our results should assist in resolving the long-standing problem of inferring the evolution of spliceosomal introns

In search of lost introns

Many fundamental questions concerning the emergence and subsequent evolution of eukaryotic exon-intron organization are still unsettled. Genome-scale comparative studies, which can shed light on crucial aspects of eukaryotic evolution, require adequate computational tools. We describe novel computational methods for studying spliceosomal intron evolution. Our goal is to give a reliable characterization of the dynamics of intron evolution. Our algorithmic innovations address the identification of orthologous introns, and the likelihood-based analysis of intron data. We discuss a compression method for the evaluation of the likelihood function, which is noteworthy for phylogenetic likelihood problems in general. We prove that after $O(nL)$ preprocessing time, subsequent evaluations take $O(nL/\log L)$ time almost surely in the Yule-Harding random model of $n$-taxon phylogenies, where $L$ is the input sequence length. We illustrate the practicality of our methods by compiling and analyzing a data set involving 18 eukaryotes, more than in any other study to date. The study yields the surprising result that ancestral eukaryotes were fairly intron-rich. For example, the bilaterian ancestor is estimated to have had more than 90% as many introns as vertebrates do now

A Detailed History of Intron-rich Eukaryotic Ancestors Inferred from a Global Survey of 100 Complete Genomes

Protein-coding genes in eukaryotes are interrupted by introns, but intron densities widely differ between eukaryotic lineages. Vertebrates, some invertebrates and green plants have intron-rich genes, with 6–7 introns per kilobase of coding sequence, whereas most of the other eukaryotes have intron-poor genes. We reconstructed the history of intron gain and loss using a probabilistic Markov model (Markov Chain Monte Carlo, MCMC) on 245 orthologous genes from 99 genomes representing the three of the five supergroups of eukaryotes for which multiple genome sequences are available. Intron-rich ancestors are confidently reconstructed for each major group, with 53 to 74% of the human intron density inferred with 95% confidence for the Last Eukaryotic Common Ancestor (LECA). The results of the MCMC reconstruction are compared with the reconstructions obtained using Maximum Likelihood (ML) and Dollo parsimony methods. An excellent agreement between the MCMC and ML inferences is demonstrated whereas Dollo parsimony introduces a noticeable bias in the estimations, typically yielding lower ancestral intron densities than MCMC and ML. Evolution of eukaryotic genes was dominated by intron loss, with substantial gain only at the bases of several major branches including plants and animals. The highest intron density, 120 to 130% of the human value, is inferred for the last common ancestor of animals. The reconstruction shows that the entire line of descent from LECA to mammals was intron-rich, a state conducive to the evolution of alternative splicing

Intron Dynamics in Ribosomal Protein Genes

The role of spliceosomal introns in eukaryotic genomes remains obscure. A large scale analysis of intron presence/absence patterns in many gene families and species is a necessary step to clarify the role of these introns. In this analysis, we used a maximum likelihood method to reconstruct the evolution of 2,961 introns in a dataset of 76 ribosomal protein genes from 22 eukaryotes and validated the results by a maximum parsimony method. Our results show that the trends of intron gain and loss differed across species in a given kingdom but appeared to be consistent within subphyla. Most subphyla in the dataset diverged around 1 billion years ago, when the “Big Bang” radiation occurred. We speculate that spliceosomal introns may play a role in the explosion of many eukaryotes at the Big Bang radiation

Patterns of intron gain and conservation in eukaryotic genes

<p>Abstract</p> <p>Background:</p> <p>The presence of introns in protein-coding genes is a universal feature of eukaryotic genome organization, and the genes of multicellular eukaryotes, typically, contain multiple introns, a substantial fraction of which share position in distant taxa, such as plants and animals. Depending on the methods and data sets used, researchers have reached opposite conclusions on the causes of the high fraction of shared introns in orthologous genes from distant eukaryotes. Some studies conclude that shared intron positions reflect, almost entirely, a remarkable evolutionary conservation, whereas others attribute it to parallel gain of introns. To resolve these contradictions, it is crucial to analyze the evolution of introns by using a model that minimally relies on arbitrary assumptions.</p> <p>Results:</p> <p>We developed a probabilistic model of evolution that allows for variability of intron gain and loss rates over branches of the phylogenetic tree, individual genes, and individual sites. Applying this model to an extended set of conserved eukaryotic genes, we find that parallel gain, on average, accounts for only ~8% of the shared intron positions. However, the distribution of parallel gains over the phylogenetic tree of eukaryotes is highly non-uniform. There are, practically, no parallel gains in closely related lineages, whereas for distant lineages, such as animals and plants, parallel gains appear to contribute up to 20% of the shared intron positions. In accord with these findings, we estimated that ancestral introns have a high probability to be retained in extant genomes, and conversely, that a substantial fraction of extant introns have retained their positions since the early stages of eukaryotic evolution. In addition, the density of sites that are available for intron insertion is estimated to be, approximately, one in seven basepairs.</p> <p>Conclusion:</p> <p>We obtained robust estimates of the contribution of parallel gain to the observed sharing of intron positions between eukaryotic species separated by different evolutionary distances. The results indicate that, although the contribution of parallel gains varies across the phylogenetic tree, the high level of intron position sharing is due, primarily, to evolutionary conservation. Accordingly, numerous introns appear to persist in the same position over hundreds of millions of years of evolution. This is compatible with recent observations of a negative correlation between the rate of intron gain and coding sequence evolution rate of a gene, suggesting that at least some of the introns are functionally relevant.</p

Malin: maximum likelihood analysis of intron evolution in eukaryotes

Summary: Malin is a software package for the analysis of eukaryotic gene structure evolution. It provides a graphical user interface for various tasks commonly used to infer the evolution of exon–intron structure in protein-coding orthologs. Implemented tasks include the identification of conserved homologous intron sites in protein alignments, as well as the estimation of ancestral intron content, lineage-specific intron losses and gains. Estimates are computed either with parsimony, or with a probabilistic model that incorporates rate variation across lineages and intron sites

Patterns of gene duplication and intron loss in the ENCODE regions suggest a confounding factor

AbstractThe exon–intron structure of eukaryotic genes allows for phenomena such as alternative splicing, nonsense-mediated decay, and regulation through untranslated regions. However, the evolution of the exon structure of genes is not well elucidated because of limited and phylogenetically sparse data sets. In this study, we use the phylogenetically diverse sequencing of the ENCODE regions to study gene structure evolution in mammalian genomes. This first phylogenetically diverse study of gene structure changes offers insights into the mode and tempo of mammalian gene structure evolution. The genes undergoing structure changes appear to be moderately to highly expressed in germline cells and show levels of selection similar to those of other ENCODE genes. Patterns of gene duplication of the affected genes are more complex than expected. The number of sampled genomes is sufficiently dense to infer that certain gene duplications happened after intron loss. Thus, although gene duplication is highly correlated with intron loss, we conclude that structural changes in genes are not necessarily due to a loss of constraint following gene duplication as previously suggested

Evolution of spliceosomal introns following endosymbiotic gene transfer

<p>Abstract</p> <p>Background</p> <p>Spliceosomal introns are an ancient, widespread hallmark of eukaryotic genomes. Despite much research, many questions regarding the origin and evolution of spliceosomal introns remain unsolved, partly due to the difficulty of inferring ancestral gene structures. We circumvent this problem by using genes originated by endosymbiotic gene transfer, in which an intron-less structure at the time of the transfer can be assumed.</p> <p>Results</p> <p>By comparing the exon-intron structures of 64 mitochondrial-derived genes that were transferred to the nucleus at different evolutionary periods, we can trace the history of intron gains in different eukaryotic lineages. Our results show that the intron density of genes transferred relatively recently to the nuclear genome is similar to that of genes originated by more ancient transfers, indicating that gene structure can be rapidly shaped by intron gain after the integration of the gene into the genome and that this process is mainly determined by forces acting specifically on each lineage. We analyze 12 cases of mitochondrial-derived genes that have been transferred to the nucleus independently in more than one lineage.</p> <p>Conclusions</p> <p>Remarkably, the proportion of shared intron positions that were gained independently in homologous genes is similar to that proportion observed in genes that were transferred prior to the speciation event and whose shared intron positions might be due to vertical inheritance. A particular case of parallel intron gain in the <it>nad7 </it>gene is discussed in more detail.</p

Analysis of Ribosomal Protein Gene Structures: Implications for Intron Evolution

Many spliceosomal introns exist in the eukaryotic nuclear genome. Despite much research, the evolution of spliceosomal introns remains poorly understood. In this paper, we tried to gain insights into intron evolution from a novel perspective by comparing the gene structures of cytoplasmic ribosomal proteins (CRPs) and mitochondrial ribosomal proteins (MRPs), which are held to be of archaeal and bacterial origin, respectively. We analyzed 25 homologous pairs of CRP and MRP genes that together had a total of 527 intron positions. We found that all 12 of the intron positions shared by CRP and MRP genes resulted from parallel intron gains and none could be considered to be “conserved,” i.e., descendants of the same ancestor. This was supported further by the high frequency of proto-splice sites at these shared positions; proto-splice sites are proposed to be sites for intron insertion. Although we could not definitively disprove that spliceosomal introns were already present in the last universal common ancestor, our results lend more support to the idea that introns were gained late. At least, our results show that MRP genes were intronless at the time of endosymbiosis. The parallel intron gains between CRP and MRP genes accounted for 2.3% of total intron positions, which should provide a reliable estimate for future inferences of intron evolution