This page contains information related to Sullivan, Reitzel, and Finnerty (2006, Genome Informatics, Vol. 17). This publication describes a comparative genomic analysis which builds upon that of Rogozin et al. (Current Biology, 2003, 13:1512-1517). Our analysis indicates (1) that early animal genomes were intron-rich, (2) that a large fraction of introns present within the human genome likely originated early in evolution, before the cnidarian-bilaterian split, some 600 million years ago, and (3) that there has been a high degree of intron loss during the evolution of the protostome lineage leading to the fruitfly, mosquito, and nematode.
This page contains: 1) a summary of the background and results of our analyses, 2) a link to the Genome Informatics publication, and 3) SUPPLEMENTAL DATA relating to the Genome Informatics publication, including our alignments and intron matrices.
Please send further inquries, comments, or suggestions to busully at bu.edu
Recent experimental and bioinformatic analyses have revealed a number of functions of intronic sequence. Sequence elements within introns may modulate gene expression by acting as transcriptional enhancers or via recruitment of the exon junction complex. Binding of this complex to a nascent RNA transcript allows enhanced cytoplasmic polysome association, increasing translation efficiency of transcripts. Similarly, the splicing process has been shown to aid in the recruitment of proteins involved in mRNA localization. Additionally, sequences within introns may code for snRNA genes.
Introns also impact genome evolution. Alternative splicing, facilitated by intron presence, accounts for a large degree of proteome diversity in a number of eukaryotic organisms. The number of splice variants encoded within the 95 exon locus of Drosophila Dscam (38016) is more than twice the number of genes believed to be encoded in the D. melanogaster genome. Additionally, introns accelerate genome evolution by facilitating exon shuffling. There is a positive correlation between intron length and the frequency of homologous recombination between exons: longer intervening sequence between exons will increase the odds of a recombination event. Recombination within intronic sequence also eliminates the requirement that such a crossover event occurs in the same reading frame.
To test the extent to which intron placement is evolutionarily conserved in eukaryotes, Rogozin et al. (Current Biology, 2003, 13:1512-1517) analyzed the positions of introns in a diverse range of eukaryotic organisms including the mustard plant Arabidopsis thaliana, the apicomplexan protozoan Plasmodium falciparum, two yeast species, (Saccharomyces cerevisiae and Schizosaccharomyces pombe), three protostome animals (Anopholes gambiae, Caenorhabditis elegans, and Drosophila melanogaster), and human, a representative deuterostome animal (Figure 1). The analysis revealed high concordance between taxa in the placement of introns within conserved protein coding regions of orthologous genes. Surprisingly, human shared more cumulative introns with Arabidopsis (14%) than with any other taxon analyzed. This resemblance between Arabidopsis and human suggests that many introns were present very early in eukaryotic evolution, prior to the evolutionary divergence between plants and animals, and that the locations of these introns have been conserved. If the resemblance between plants and humans is attributable to homology and not to convergence, then the lower level of similarity between humans and other animals must be due to lineage specific intron-losses.
The resemblance between humans and plants suggests strong stabilizing selection on intron location. However, the lesser resemblance between humans and the other animals in the study suggests that this stabilizing selection may have been relaxed in one or more protostome lineages. Recent comparative genomic analyses involving members of the basal metazoan phylum Cnidaria have suggested that the model protostomes, D. melanogaster and C. elegans, are generally undergoing rapid genome evolution. In numerous instances, cnidarians have been found to share genes with humans that are lacking from these two protostome animals .
In order to investigate the hypothesis that the protostome model systems have undergone accelerated intron loss, we examined intron location in the sea anemone Nematostella vectensis, a representative cnidarian. Barring lineage-specific intron loss, no introns that are conserved between humans and cnidarians could be missing from the genomes of A. gambiae, C. elegans, and D. melanogaster because protostomes and deuterostomes share a common ancestor to the exclusion of cnidarians (Figure 1). We examined all of the 684 eukaryote orthologous genes (KOGs) studied by Rogozin et al. (Current Biology, 2003, 13:1512-1517) for which a suitable N. vectensis EST is available and discovered a high degree of intron concordance between N. vectensis and human genes.
Results
Within conserved regions of these 348 KOGs, N. vectensis possesses 1459 introns, and humans possess 1246 introns. Of the total number of introns found in sea anemone and human, forty-seven percent (862/1843) occur at the same position within KOGs in both species, with 69% of human introns present in N. vectensis (862/1246). Using intron presence as a character in phylogenetic analysis reveals that N. vectensis and human form a clade to the exclusion of all other taxa (Figure 2) This concordance between human and sea anemone is more than triple the concordance between human and the other animal models in the analysis. Phylogenetic character state reconstruction indicates that for conserved regions of these 348 KOGs, 880 introns were present in the cnidarian-bilaterian ancestor (Figure 3). Subsequently, pervasive intron loss occurred in the protostome lineage, prior to the divergence of the Dipterans (A. gambiae and D. melanogaster) and C. elegans. Our data support the hypothesis that strong selective pressure has acted to maintain placement of these introns in extremely divergent lineages with disparate morphologies and life histories.
