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Molecular biology and evolution [journal]
- Purifying selection on splice-related motifs, not expression level nor RNA folding, explains nearly all constraint on human lincRNAs. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Aug 25.
There are two strong and equally important predictors of rates of human protein evolution: the amount the gene is expressed and the proportion of exonic sequence devoted to control splicing, mediated largely by selection on exonic splice enhancer (ESE) motifs. Is the same true for non-coding RNAs, known to be under very weak purifying selection? Prior evidence suggests that selection at splice sites in lincRNAs is important. We now report multiple lines of evidence indicating that the great majority of purifying selection operating on lincRNAs in humans is splice-related. Splice related parameters explain much of the between-gene variation in evolutionary rate in humans. Expression rate is not a relevant predictor, although expression breadth is weakly so. In contrast to protein coding RNAs, we observe no relationship between evolutionary rate and lincRNA stability. As in protein coding genes, ESEs are especially abundant near splice junctions and evolve slower than non-ESE sequence equidistant from boundaries. Nearly all constraint in lincRNAs is at exon ends (N.B. the same is not witnessed in Drosophila). While we cannot definitely answer the question as to why splice-related selection is so important, we find no evidence that splicing might enable the nonsense mediated decay pathway to capture transcripts incorrectly processed by ribosomes. We find evidence consistent with the notion that splicing modifies the underlying chromatin through recruitment of splice-coupled chromatin modifiers, such as CHD1, which in turn might modulate neighbour gene activity. We conclude that most selection on human lincRNAs is splice mediated and suggest that the possibility of splice-chromatin coupling is worthy of further scrutiny.
- Drosophila suzukii: the genetic footprint of a recent, world-wide invasion. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Aug 25.
Native to Asia, the soft-skinned fruit pest Drosophila suzukii has recently invaded the United States and Europe. The eastern United States represents the most recent expansion of their range, and presents an opportunity to test alternative models of colonization history. Here we investigate the genetic population structure of this invasive fruit fly, with a focus on the eastern United States. We sequenced six X-linked gene fragments from 246 individuals collected from a total of 12 populations. We examine patterns of genetic diversity within and between populations and explore alternative colonization scenarios using Approximate Bayesian Computation. Our results indicate high levels of nucleotide diversity in this species and suggest that the recent invasions of Europe and the continental United States are independent demographic events. More broadly speaking, our results highlight the importance of integrating population structure into demographic models, particularly when attempting to reconstruct invasion histories. Finally, our simulation results illustrate the general challenge of reconstructing invasion histories using genetic data and suggest that genome-level data are often required to distinguish among alternative demographic scenarios.
- Positive selection during the evolution of the blood coagulation factors in the context of their disease-causing mutations. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Aug 25.
Blood coagulation occurs through a cascade of enzymes and cofactors that produces a fibrin clot, while otherwise maintaining haemostasis. The 11 human coagulation factors (FG, FII-FXIII) have been identified across all vertebrates, suggesting that they emerged with the first vertebrates around 500 Mya. Human FVIII, FIX and FXI are associated with thousands of disease-causing mutations. Here we evaluated the strength of selective pressures on the 14 genes coding for the 11 factors during vertebrate evolution, and compared these with human mutations in FVIII, FIX and FXI. Positive selection was identified for fibrinogen (FG), FIII, FVIII, FIX and FX in the mammalian Primates and Laurasiatheria and the Sauropsida (reptiles and birds). This showed that the coagulation system in vertebrates was under strong selective pressures, perhaps to adapt against blood-invading pathogens. The comparison of these results with disease-causing mutations reported in FVIII, FIX and FXI showed that the number of disease-causing mutations and the probability of positive selection were inversely related to each other. It was concluded that when a site was under positive selection, it was less likely to be associated with disease-causing mutations. In contrast, sites under negative selection were more likely to be associated with disease-causing mutations and be destabilizing. A residue-by-residue comparison of the FVIII, FIX and FXI sequence alignments confirmed this. This improved understanding of evolutionary changes in FVIII, FIX and FXI provided greater insight into disease-causing mutations, and better assessments of the codon sites that may be mutated in applications of gene therapy.
- Subscription page. [Journal Article]
- Mol Biol Evol 2014 Sep; 31(9):i4.
- SMBE Editors and Council. [Journal Article]
- Mol Biol Evol 2014 Sep; 31(9):i3.
- Associate editors. [Journal Article]
- Mol Biol Evol 2014 Sep; 31(9):i2.
- Cover. [Journal Article]
- Mol Biol Evol 2014 Sep; 31(9):i1.
- For bats and dolphins, hearing gene prestin adapted for echolocation. [Journal Article]
- Mol Biol Evol 2014 Sep; 31(9):2552.
- Eukaryotic Penelope-Like Retroelements Encode Hammerhead Ribozyme Motifs. [LETTER]
- Mol Biol Evol 2014 Aug 18.
Small self-cleaving RNAs, such as the paradigmatic Hammerhead ribozyme (HHR), have been recently found widespread in DNA genomes across all kingdoms of life. In this work, we found that new HHR variants are preserved in the ancient family of Penelope-like elements (PLEs), a group of eukaryotic retrotransposons regarded as exceptional for encoding telomerase-like retrotranscriptases and spliceosomal introns. Our bioinformatic analysis revealed not only the presence of minimalist HHRs in the two flanking repeats of PLEs but also their massive and widespread occurrence in metazoan genomes. The architecture of these ribozymes indicates that they may work as dimers, although their low self-cleavage activity in vitro suggests the requirement of other factors in vivo. In plants, however, PLEs show canonical HHRs, whereas fungi and protist PLEs encode ribozyme variants with a stable active conformation as monomers. Overall, our data confirm the connection of self-cleaving RNAs with eukaryotic retroelements and unveil these motifs as a significant fraction of the encoded information in eukaryotic genomes.
- Parallel evolution of tetrodotoxin resistance in three voltage-gated sodium channel genes in the garter snake Thamnophis sirtalis. [JOURNAL ARTICLE]
- Mol Biol Evol 2014 Aug 18.
Members of a gene family expressed in a single species often experience common selection pressures. Consequently, the molecular basis of complex adaptations may be expected to involve parallel evolutionary changes in multiple paralogs. Here, we use BAC library scans to investigate the evolution of the voltage-gated sodium channel (Nav) family in the garter snake Thamnophis sirtalis, a predator of highly toxic Taricha newts. Newts possess tetrodotoxin (TTX), which blocks voltage-gated sodium channels, arresting action potentials in nerves and muscle. Some Thamnophis populations have evolved resistance to extremely high levels of TTX. Previous work has identified amino acid sites in the skeletal muscle sodium channel Nav1.4 that confer resistance to TTX and vary across populations. We identify parallel evolution of TTX resistance in two additional Nav paralogs, Nav1.6 and 1.7, which are known to be expressed in the peripheral nervous system and should thus be exposed to ingested TTX. Each paralog contains at least one TTX-resistant substitution identical to a substitution previously identified in Nav1.4. These sites are fixed across populations, suggesting that the resistant peripheral nerves antedate resistant muscle. In contrast, three sodium channels expressed solely in the central nervous system (Nav1.1-1.3) showed no evidence of TTX resistance, consistent with protection from toxins by the blood-brain barrier. We also report the exon-intron structure of six Nav paralogs, the first such analysis for snake genes. Our results demonstrate that the molecular basis of adaptation may be both repeatable across members of a gene family and predictable based on functional considerations.