Biomedical subjects

Scott William Roy

Publications and source records attributed to Scott William Roy.

10 recordsLinked to original sources

PubMed2006

Patterns of intron loss and gain in plants: intron loss-dominated evolution and genome-wide comparison of O. sativa and A. thaliana.

Numerous previous studies have elucidated 2 surprising patterns of spliceosomal intron evolution in diverse eukaryotes over the past roughly 100 Myr. First, rates of recent intron gain in a wide variety of eukaryotic lineages have been surprisingly low, far too low to explain modern intron densities. Second, intron losses have outnumbered intron gains over a variety of lineages. For several reasons, land plants might be expected to have comparatively high rates of intron gain and thus to represent a possible exception to this pattern. However, we report several studies that indicate low rates of intron gain and an excess of intron losses over intron gains in a variety of plant lineages. We estimate that intron losses have outnumbered intron gains in recent evolution in Arabidopsis thaliana (roughly 12.6 times more losses than gains), Oryza sativa (9.8 times), the green alga Chlamydomonas reinhardtii (5.1 times), and the Bigelowiella natans nucleomorph, an enslaved green algal nucleus (2.8 times). We estimate that during recent evolution, A. thaliana and O. sativa have experienced very low rates of intron gain of around one gain per gene per 2.6-8.0 billion years. In addition, we compared 8,258 pairs of putatively orthologous A. thaliana-O. sativa genes. We found that 5.3% of introns in conserved coding regions are species-specific. Observed species-specific A. thaliana and O. sativa introns tend to be exact and to lie adjacent to each other along the gene, in a pattern suggesting mRNA-mediated intron loss. Our results underscore that low intron gain rates and intron number reduction are common features of recent eukaryotic evolution. This pattern implies that rates of intron creation were higher during earlier periods of evolution and further focuses attention on the causes of initial intron proliferation.

Amino Acid Sequence↗

PubMed2006

Large-scale intron conservation and order-of-magnitude variation in intron loss/gain rates in apicomplexan evolution.

The age of modern introns and the evolutionary forces controlling intron loss and gain remain matters of much debate. In the case of the apicomplexan malaria parasite Plasmodium falciparum, previous studies have shown that while the positions of two thirds of P. falciparum introns are not shared with surveyed non-apicomplexans (leaving open the possibility that they were relatively recently gained), 99.1% are shared with Plasmodium yoelii, which diverged from P. falciparum at least 100 Mya. We show here that 60.6% of P. falciparum intron positions in conserved regions are shared with the distantly related apicomplexan Theileria parva, whereas only 18.2% of introns in the more intron-rich T. parva are shared with P. falciparum. Comparison of 3305 pairs of orthologous genes between T. parva and Theileria annulata showed that 7089/7111 (99.7%) introns in conserved regions are shared between species. These levels of conservation imply significant differences in rates of intron loss and gain through apicomplexan history. Because transposable elements (TEs) and/or (often TE-encoded) reverse transcriptase are implicated in models of intron loss and gain, the observed low rates of intron loss and gain in recent Plasmodium and Theileria evolution are consistent with the lack of known TE in those groups. We suggest that intron loss/gain in some eukaryotic lineages may be concentrated in relatively short episodes coincident with occasional TE invasions.

Animals↗

PubMed2006

Smoke without fire: most reported cases of intron gain in nematodes instead reflect intron losses.

Identification of recently gained spliceosomal introns would provide crucial evidence in the continuing debate concerning the age and evolutionary significance of introns. A previously published genomic analysis reported to have identified 122 introns that had been gained since the divergence of the nematodes Caenorhabidits elegans and Caenorhabditis briggsae approximately 100 MYA. However, using newly available genomic sequence from additional Caenorhabditis species, we show that 74% (60/81) of the reported gains in C. elegans are present in a C. briggsae relative. This pattern indicates that these introns represent losses in C. briggsae, not gains in C. elegans. In addition, 61% (25/41) of the reported gains in C. briggsae are present in the more distant C. briggsae relative, in a pattern suggesting that additional reported gains in C. elegans and/or C. briggsae may in fact represent unrecognized losses. These results underscore the dominance of intron loss over intron gain in recent eukaryotic evolution, the pitfalls associated with parsimony in inferring intron gains, and the importance of genomic sequencing of clusters of closely related species for drawing accurate inferences about genome evolution.

Amino Acid Sequence↗

PubMed2006

Very little intron gain in Entamoeba histolytica genes laterally transferred from prokaryotes.

The evolution of spliceosomal introns remains intensely debated. We studied 96 Entamoeba histolytica genes previously identified as having been laterally transferred from prokaryotes, which were presumably intronless at the time of transfer. Ninety out of the 96 are also present in the reptile parasite Entamoeba invadens, indicating lateral transfer before the species' divergence approximately 50 MYA. We find only 2 introns, both shared with E. invadens. Thus, no intron gains have occurred in approximately 50 Myr, implying a very low rate of intron gain of less than one gain per gene per approximately 4.5 billion years. Nine other predicted introns are due to annotation errors reflecting apparent mistakes in the E. histolytica genome assembly. These results underscore the massive differences in intron gain rates through evolution.

Amino Acid Sequence↗

PubMed2006

Very little intron loss/gain in Plasmodium: intron loss/gain mutation rates and intron number.

We compared intron positions in conserved regions of 3479 orthologous gene pairs from Plasmodium falciparum and Plasmodium yoelii, which likely diverged >or=100 million years ago (Mya). Only 27 out of 2212 positions were specific to one of the two species. Intron presence in related species shows that at least 19 and possibly 26 of the changes are due to intron loss, depending on phylogeny. The implied intron loss and gain rates are much lower than previously estimated for nematodes, arthropods, fungi, and plants, and are comparable only with the rates in vertebrates. That all observed changes were exact, occurring without loss or gain of flanking coding sequence, suggests intron loss via an mRNA intermediate, as does a nonsignificant trend toward loss of introns at adjacent positions. Many of the intron changes occurred in genes encoding proteins involved in nucleic acid-related processes, as previously found for intron gains in nematodes. Two changes occurred in the chloroquine resistance transporter, suggesting a role for positive selection in intron loss in Plasmodium. The dearth of intron loss and gain could be explained by the lack of known transposable elements in Plasmodium, since transposable elements and/or reverse transcriptase are thought to be necessary for both processes. The observed pattern suggests that the availability of stochastic intron loss and gain mutations can be a major determinant of changes in intron number.

Alternative Splicing↗

PubMed2006

The evolution of spliceosomal introns: patterns, puzzles and progress.

The origins and importance of spliceosomal introns comprise one of the longest-abiding mysteries of molecular evolution. Considerable debate remains over several aspects of the evolution of spliceosomal introns, including the timing of intron origin and proliferation, the mechanisms by which introns are lost and gained, and the forces that have shaped intron evolution. Recent important progress has been made in each of these areas. Patterns of intron-position correspondence between widely diverged eukaryotic species have provided insights into the origins of the vast differences in intron number between eukaryotic species, and studies of specific cases of intron loss and gain have led to progress in understanding the underlying molecular mechanisms and the forces that control intron evolution.

Animals↗

PubMed2005

Rates of intron loss and gain: implications for early eukaryotic evolution.

We study the intron-exon structures of 684 groups of orthologs from seven diverse eukaryotic genomes and provide maximum likelihood estimates for rates and numbers of intron losses and gains in these same genes for a variety of lineages. Rates of intron loss vary from approximately 2 x 10(-9) to 2 x 10(-10) per year. Rates of gain vary from 6 x 10(-13) to 4 x 10(-12) per possible intron insertion site per year. There is an inverse correspondence between rates of intron loss and gain, leading to a 20-fold variation among lineages in the ratio of the rates of the two processes. The observed rates of intron gain are insufficient to explain the large number of introns estimated to have been present in the plant-animal ancestor, suggesting that introns present in early eukaryotes may have been created by a fundamentally different process than more recently gained introns.

Animals↗

PubMed2005

Resolution of a deep animal divergence by the pattern of intron conservation.

The relationship between three biologically important groups, arthropods, nematodes, and deuterostomes, remains unresolved. It is unknown whether arthropods are more closely related to nematodes (consistent with the "ecdysozoa" hypothesis) or to deuterostomes (consistent with "coelomata"). We present a method in which we use the pattern of spliceosomal intron conservation to develop a series of inequalities that characterize each possible relationship. We find that only the ecdysozoa grouping satisfies these predictions, with P < 10(-6). Simulations show that our method, unlike some previous methods, is largely insensitive to rate variation between branches.

Animals↗

PubMed2003

Recent evidence for the exon theory of genes.

I provide a history of the Exon Theory of Genes, a theory that holds that introns are extremely ancient characteristics of genes and that early genes were created through the intron-mediated shuffling of exons. The theory has existed since the late seventies. An uncompromising version of the theory, in which all introns were considered to be ancient, dominated the early work. However, in the late eighties and early nineties evidence arose that at least some introns are more recently acquired. Due to the previously overly polarized nature of the debate, many results that demonstrated the existence of recent introns have been interpreted by some as evidence that all introns are late, leading some to believe that the theory is no longer a viable theory. However, recent work emphasizes a mixed model, in which some introns are ancient and some new. This model has proven to provide impressive explanatory power for a broad array of observations. Thus, this moderated form of the Exon Theory of Genes still offers a coherent picture of the origin and evolutionary history of the intron-exon structure of eukaryotic genes.

Evolution, Molecular↗

PubMed2002

The signal of ancient introns is obscured by intron density and homolog number.

In ancient genes whose products have known 3-dimensional structures, an excess of phase zero introns (those that lie between the codons) appear in the boundaries of modules, compact regions of the polypeptide chain. These excesses are highly significant and could support the hypothesis that ancient genes were assembled by exon shuffling involving compact modules. (Phase one and two introns, and many phase zero introns, appear to arise later.) However, as more genes, with larger numbers of homologs and intron positions, were examined, the effects became smaller, dropping from a 40% excess to an 8% excess as the number of intron positions increased from 570 to 3,328, even though the statistical significance remained strong. An interpretation of this behavior is that novel inserted positions appearing in homologs washed out the signal from a finite number of ancient positions. Here we show that this is likely to be the case. Analyses of intron positions restricted to those in genes for which relatively few intron positions from homologs are known, or to those in genes with a small number of known homologous gene structures, show a significant correlation of phase zero intron positions with the module structure, which weakens as the density of attributed intron positions or the number of homologs increases. These effects do not appear for phase one and phase two introns. This finding matches the expectation of the mixed model of intron origin, in which a fraction of phase zero introns are left from the assembly of the first genes, while other introns have been added in the course of evolution.

Evolution, Molecular↗