Low Evolutionary Rate Research Articles

Comparative sequence analyses of rhodopsin and RPE65 reveal patterns of selective constraint across hereditary retinal disease mutations.

Retinitis pigmentosa (RP) comprises several heritable diseases that involve photoreceptor, and ultimately retinal, degeneration. Currently, mutations in over 50 genes have known links to RP. Despite advances in clinical characterization, molecular characterization of RP remains challenging due to the heterogeneous nature of causal genes, mutations, and clinical phenotypes. In this study, we compiled large datasets of two important visual genes associated with RP: rhodopsin, which initiates the phototransduction cascade, and the retinoid isomerase RPE65, which regenerates the visual cycle. We used a comparative evolutionary approach to investigate the relationship between interspecific sequence variation and pathogenic mutations that lead to degenerative retinal disease. Using codon-based likelihood methods, we estimated evolutionary rates (d N/d S) across both genes in a phylogenetic context to investigate differences between pathogenic and nonpathogenic amino acid sites. In both genes, disease-associated sites showed significantly lower evolutionary rates compared to nondisease sites, and were more likely to occur in functionally critical areas of the proteins. The nature of the dataset (e.g., vertebrate or mammalian sequences), as well as selection of pathogenic sites, affected the differences observed between pathogenic and nonpathogenic sites. Our results illustrate that these methods can serve as an intermediate step in understanding protein structure and function in a clinical context, particularly in predicting the relative pathogenicity (i.e., functional impact) of point mutations and their downstream phenotypic effects. Extensions of this approach may also contribute to current methods for predicting the deleterious effects of candidate mutations and to the identification of protein regions under strong constraint where we expect pathogenic mutations to occur.

Evaluation of 5.8S rRNA to identify Penaeus semisulcatus and its subspecies, Penaeus semisulcatus persicus (Penaeidae) and some Decapoda species

The green tiger prawn, Penaeus semisulcatus is one of the most important members of the family Penaeidae in the Persian Gulf. Based on the morphological characteristics, two groups, including P. semisulcatus and its subspecies viz. P. s. persicus are recognized. This study was conducted to investigate the genetic distance between P. semisulcatus and P. s. persicus by analyzing partial sequence of 5.8S rRNA. Another objective of this study is to evaluate the ability of 5.8S rRNA to identify the species of Decapoda. The results indicated that the 5.8S rRNA gene of both P. semisulcatus and P. s. persicus were exactly identical, and sequence variation was not observed. The results also indicated that 5.8S rRNA sequences between species of the same genus of analysed species of Decapoda are conserved, and no genetic distance was observed in species level. The low evolutionary rate and efficient conservation of the 5.8S rRNA can be attributed to its role in the translation process.

Phylodynamic reconstruction of the spatiotemporal transmission and demographic history of coxsackievirus B2.

BackgroundStudies regarding coxsackievirus (CV) tend to focus on epidemic outbreaks, an imbalanced topology is considered to be an indication of acute infection with partial cross-immunity. In enteroviruses, a clear understanding of the characteristics of tree topology, transmission, and its demographic dynamics in viral succession and circulation are essential for identifying prevalence trends in endemic pathogens such as coxsackievirus B2 (CV-B2). This study applied a novel Bayesian evolutionary approach to elucidate the phylodynamic characteristics of CV-B2. A dataset containing 51 VP1 sequences and a dataset containing 34 partial 3Dpol sequencing were analyzed, where each dataset included Taiwan sequences isolated during 1988–2013.ResultsFour and five genotypes were determined based on the 846-nucleotide VP1 and 441-nucleotide 3Dpol (6641–7087) regions, respectively, with spatiotemporally structured topologies in both trees. Some strains with tree discordance indicated the occurrence of recombination in the region between the VP1 and 3Dpol genes. The similarities of VP1 and 3Dpol gene were 80.0 %–96.8 % and 74.7 %–91.9 %, respectively. Analyses of population dynamics using VP1 dataset indicated that the endemic CV-B2 has a small effective population size. The balance indices, high similarity, and low evolutionary rate in the VP1 region indicated mild herd immunity selection in the major capsid region.ConclusionsPhylodynamic analysis can reveal demographic trends and herd immunity in endemic pathogens.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0738-2) contains supplementary material, which is available to authorized users.

Ultrastructure and 28S rDNA phylogeny of two gregarines: Cephaloidophora cf. communis and Heliospora cf. longissima with remarks on gregarine morphology and phylogenetic analysis

S rRNA gene sequences (SSU rDNA) in gregarines are problematic for phylogenetic analysis, mainly due to artifacts related to long branch attraction (LBA). In this study, we sequenced 18S rRNA (SSU rRNA), 5.8S rRNA, and 28S rRNA (LSU rRNA) genes of two gregarine species from crustacean hosts (gregarine superfamily Cephaloidophoroidea): Cephaloidophora cf. communis from a marine cirripedian Balanus balanus (White Sea), and Heliospora cf. longissima from the freshwater amphipods, Eulimnogammarus verrucosus and E. vittatus (Lake Baikal). Phylogenetic analyses of SSU rDNA sequences failed to produce a robust tree topology, for a limited taxon sample (31 operational taxonomic units (OTU), based on 1,604 sites), while LSU (2,869 sites), and concatenated dataset based on SSU, 5.8S, and LSU (4,627 sites) produced more consistent tree topologies for the same taxon sample. Analyses testing for LBA-influence were negative, therefore we suggested that the main reason of the failed topologies in SSU rDNA analyses is insufficient data (insufficient taxon sampling and limited molecular data), rather than LBA. Possible advantages of Bayesian analyses, compared to Maximum Likelihood, and usage of LSU rDNA within the context of apicomplexan phylogenetics were discussed. One of the advantages of LSU is likely its lower rate of evolution in long-branching apicomplexans (e.g., gregarines), relative to other (non-long-branching) apicomplexans, compared to SSU rDNA. Ultrastructure of the epicytic folds was studied. There are 3 to 5 apical arcs (also known as rippled dense structures) and 2 to 5 apical filaments in the tops of the folds. This small number of the apical structures fits into morphological diversity of the epicyte in other Cephaloidophoroidea, but this is not a synapomorphy of the group because this was also detected in several unrelated gregarines. C. cf. communis was found to contain a septum between the epimerite and the protomerite, which has not been reported in other gregarines. More exact terminology, which takes into account number of body sections and septa, is proposed for morphological descriptions of trophozoites and free mature gamonts of gregarines. In accordance with this, C. cf. communis gamonts are tricystid and biseptate, whereas H. cf. longis­ sima gamonts are tricystid and uniseptate, similar to other eugregarines.

RIG-I Signaling Is Essential for Influenza B Virus-Induced Rapid Interferon Gene Expression.

Influenza B virus causes annual epidemics and, along with influenza A virus, accounts for substantial disease and economic burden throughout the world. Influenza B virus infects only humans and some marine mammals and is not responsible for pandemics, possibly due to a very low frequency of reassortment and a lower evolutionary rate than that of influenza A virus. Influenza B virus has been less studied than influenza A virus, and thus, a comparison of influenza A and B virus infection mechanisms may provide new insight into virus-host interactions. Here we analyzed the early events in influenza B virus infection and interferon (IFN) gene expression in human monocyte-derived macrophages and dendritic cells. We show that influenza B virus induces IFN regulatory factor 3 (IRF3) activation and IFN-λ1 gene expression with faster kinetics than does influenza A virus, without a requirement for viral protein synthesis or replication. Influenza B virus-induced activation of IRF3 required the fusion of viral and endosomal membranes, and nuclear accumulation of IRF3 and viral NP occurred concurrently. In comparison, immediate early IRF3 activation was not observed in influenza A virus-infected macrophages. Experiments with RIG-I-, MDA5-, and RIG-I/MDA5-deficient mouse fibroblasts showed that RIG-I is the critical pattern recognition receptor needed for the influenza B virus-induced activation of IRF3. Our results show that innate immune mechanisms are activated immediately after influenza B virus entry through the endocytic pathway, whereas influenza A virus avoids early IRF3 activation and IFN gene induction. Recently, a great deal of interest has been paid to identifying the ligands for RIG-I under conditions of natural infection, as many previous studies have been based on transfection of cells with different types of viral or synthetic RNA structures. We shed light on this question by analyzing the earliest step in innate immune recognition of influenza B virus by human macrophages. We show that influenza B virus induces IRF3 activation, leading to IFN gene expression after viral RNPs (vRNPs) are released into the cytosol and are recognized by RIG-I receptor, meaning that the incoming influenza B virus is already able to activate IFN gene expression. In contrast, influenza A (H3N2) virus failed to activate IRF3 at very early times of infection, suggesting that there are differences in innate immune recognition between influenza A and B viruses.

Mitochondrial gene order variation in the brachiopod Lingula anatina and its implications for mitochondrial evolution in lophotrochozoans

Vertebrate mitochondrial (mt) genomes display highly conserved gene order and relatively low evolutionary rates. However, these features are variable in marine invertebrates. Here we present the mt genome of the lingulid brachiopod, Lingula anatina, from Amami Island, Japan, as part of the nuclear genome project. We obtain ~2000-fold coverage of the 17.9-kb mt genome using Illumina sequencing, and we identify hypervariable regions within the same individual. Transcriptome analyses show that mt transcripts are polycistronic and expressed differentially. Unexpectedly, we find that the mt gene order of Amami Lingula is completely shuffled compared to that of a specimen from Yanagawa, suggesting that there may be cryptic species. Using breakpoint distance analyses with 101 metazoan mt genomes, we show that the evolutionary history of mt gene order among lophotrochozoans is unique. Analyses of non-synonymous substitution rates reveal that mt protein-coding genes of Lingula have experienced rapid evolution comparable to that expected for interspecific comparisons. Whole genome phylogenetic analyses suggest that mt genomes have limited value for inferring the phylogenetic positions of lophotrochozoans because of their high evolutionary rates in brachiopods and bivalves.

Covariation Is a Poor Measure of Molecular Coevolution.

Recent developments in the analysis of amino acid covariation are leading to breakthroughs in protein structure prediction, protein design, and prediction of the interactome. It is assumed that observed patterns of covariation are caused by molecular coevolution, where substitutions at one site affect the evolutionary forces acting at neighboring sites. Our theoretical and empirical results cast doubt on this assumption. We demonstrate that the strongest coevolutionary signal is a decrease in evolutionary rate and that unfeasibly long times are required to produce coordinated substitutions. We find that covarying substitutions are mostly found on different branches of the phylogenetic tree, indicating that they are independent events that may or may not be attributable to coevolution. These observations undermine the hypothesis that molecular coevolution is the primary cause of the covariation signal. In contrast, we find that the pairs of residues with the strongest covariation signal tend to have low evolutionary rates, and that it is this low rate that gives rise to the covariation signal. Slowly evolving residue pairs are disproportionately located in the protein’s core, which explains covariation methods’ ability to detect pairs of residues that are close in three dimensions. These observations lead us to propose the “coevolution paradox”: The strength of coevolution required to cause coordinated changes means the evolutionary rate is so low that such changes are highly unlikely to occur. As modern covariation methods may lead to breakthroughs in structural genomics, it is critical to recognize their biases and limitations.

Evolutionary dynamics of Rh2 opsins in birds demonstrate an episode of accelerated evolution in the New World warblers (Setophaga).

Low rates of sequence evolution associated with purifying selection can be interrupted by episodic changes in selective regimes. Visual pigments are a unique system in which we can investigate the functional consequences of genetic changes, therefore connecting genotype to phenotype in the context of natural and sexual selection pressures. We study the RH2 and RH1 visual pigments (opsins) across 22 bird species belonging to two ecologically convergent clades, the New World warblers (Parulidae) and Old World warblers (Phylloscopidae) and evaluate rates of evolution in these clades along with data from 21 additional species. We demonstrate generally slow evolution of these opsins: both Rh1 and Rh2 are highly conserved across Old World and New World warblers. However, Rh2 underwent a burst of evolution within the New World genus Setophaga, where it accumulated substitutions at 6 amino acid sites across the species we studied. Evolutionary analyses revealed a significant increase in dN /dS in Setophaga, implying relatively strong selective pressures to overcome long-standing purifying selection. We studied the effects of each substitution on spectral tuning and found they do not cause large spectral shifts. Thus, substitutions may reflect other aspects of opsin function, such as those affecting photosensitivity and/or dark-light adaptation. Although it is unclear what these alterations mean for colour perception, we suggest that rapid evolution is linked to sexual selection, given the exceptional plumage colour diversification in Setophaga.

Modularity in the evolution of yeast protein interaction network.

Protein interaction networks are known to exhibit remarkable structures: scale-free and small-world and modular structures. To explain the evolutionary processes of protein interaction networks possessing scale-free and small-world structures, preferential attachment and duplication-divergence models have been proposed as mathematical models. Protein interaction networks are also known to exhibit another remarkable structural characteristic, modular structure. How the protein interaction networks became to exhibit modularity in their evolution? Here, we propose a hypothesis of modularity in the evolution of yeast protein interaction network based on molecular evolutionary evidence. We assigned yeast proteins into six evolutionary ages by constructing a phylogenetic profile. We found that all the almost half of hub proteins are evolutionarily new. Examining the evolutionary processes of protein complexes, functional modules and topological modules, we also found that member proteins of these modules tend to appear in one or two evolutionary ages. Moreover, proteins in protein complexes and topological modules show significantly low evolutionary rates than those not in these modules. Our results suggest a hypothesis of modularity in the evolution of yeast protein interaction network as systems evolution.

Molecular analysis of some camel cytochrome P450 enzymes reveals lower evolution and drug-binding properties

Camels bear unique genotypes and phenotypes for adaptation of their harsh environment. They have unique visual systems, sniffing, water metabolism, and heat-control mechanisms that are different from other creatures. The recent announcement for the complete sequence of camel genome will allow for the discovery of many secrets of camel life. In this context, the genetic bases of camel drug-metabolizing enzymes are still unknown. Furthermore, the genomic content of camel that rendered it highly susceptible to some drugs (as monensin and salinomycin) and became easily intoxicated needs to be investigated. The objectives of this work are the annotation of camel genome and retrieval of camel for cytochrome P450 (CYP) 1A1, 2C, and 3A enzymes. This is followed by comprehensive phylogenetic, evolution, molecular modeling, and docking studies. In comparison with the human enzymes, camel CYPs showed lower evolution rate, especially CYP1A1. Furthermore, the binding of monensin, salinomycin, alfa-naphthoflavone, felodepine, and ritonavir was weaker in camel enzymes. Interestingly, rerank score indicated instable binding of monensin and salinomycin with camel CYP1A1 as well as salinomycin with camel CYP2C. The results of this work suggest that camels are more susceptible to toxicity with compounds undergoing metabolic oxidation. This conclusion was based on lower evolution rate and lower binding potency of camels compared with the human enzymes.

Pediatric aplastic anemia and refractory cytopenia: A retrospective analysis assessing outcomes and histomorphologic predictors.

Pediatric acquired aplastic anemia (AA) is a bone marrow disorder that is difficult to distinguish from inherited bone marrow failure syndromes and hypocellular refractory cytopenia of childhood (RCC). Historically, patients with hypocellular RCC have been given the diagnosis of AA. To assess the clinical and histologic distinction between RCC and AA, we performed a retrospective analysis of 149 patients previously diagnosed with AA between 1976 and 2010. We evaluated event free survival (EFS), overall survival (OS), response rates to immunosuppressive therapy, treatment-related toxicities and clonal evolution. The 5-year EFS and OS were 50.8% ± 5.5% and 73.1% ± 4.7%, respectively. Patients with very severe AA had worse OS compared to patients with severe and moderately severe AA. Seventy-two patients had diagnostic pathology specimens available for review. Three pediatric hematopathologists reviewed and reclassified these specimens as AA, RCC or Other based on 2008 WHO Criteria. The concordance between pathologists in the diagnosis of AA or RCC was modest. RCC was associated with a trend toward improved OS and EFS and was not prognostic of immunosuppression therapy treatment failure. There was a low rate of clonal evolution exclusively associated with moderately severe AA. Our findings indicate that a diagnosis of RCC is difficult to establish with certainty and does not predict outcomes, calling into question the reproducibility and clinical significance of the RCC classification and warranting further studies.

European Species of Subaerial Green Alga Trentepohlia annulata (Trentepohliales, Ulvophyceae) Caused Blood Rain in Kerala, India

In 2011, isolated parts in south Indian state of Kerala as well as neighboring Sri Lanka experienced sporadic spell of red colored “blood rain”, cause of which was later attributed to terrestrial subaerial microalgae of the genus Trentepohlia. Green algae of this genus is commonly found living in symbiosis as phycobionts of lichens in the freeliving form in adjoining tropical rain forests, however, specific identity of which have never been determined. It is known that lichens disperse small algal-hyphal packages, so-called soredia, for vegetative reproduction, which can explain the content of Trentepohlia-spores in the water. Given its extraordinary spore-dispersal mechanism via rain, we were specifically interested to know species-level identity of a randomly collected Trentepohlialean algae of “blood rain” region, and to investigate the possibility that this might had been introduced from elsewhere through areal route. Results of our comparative morphology and molecular phylogenetic analyses using the nuclear ribosomal DNA Internal Transcribed Spacers region concluded that this alga is Trentepohlia annulata – a species of which no previous reports exist from India. These two geographical isolates were separated by Kimura-2-Parameter pair-wise distance of 0.06-which in turn indicate a low rate of evolution at these loci that are renowned for rapid molecular evolution, suggestive of a recent introduction. Phylogeny reconstruction using Bayesian Inference and Maximum Likelihood methods resulted in well-resolved phylograms with a robust clade composed of these isolates. This finding indicates the existence of areal dispersal of algal spores on continental and global scales through “clouds over oceans”- a phenomenon earlier reported for bacteria and fungi, but for the first time in algae.

Phylogenetic informativeness of plastid regions in inferring the species relationships amongCucumisspecies

Molecular approaches are playing major role in phylogeny reconstruction and species relationship studies. The uniparent inheritance, small size, non recombinant nature and extremely low rate of evolution of chloroplast genome make it an appropriate marker for phylogenetic studies. In the present study, phylogenetic informativeness of two coding regions, rbcL and rpoC1 and two non-coding intergenic spacers psbA-trnH and trnL-F of plastid DNA were analysed for inferring relationships among Cucumis species. Maximum evolutionary divergence was shown by trnL-F followed by psbA-trnH region. The non-coding spacers evolved 1.62 to 9 times faster than coding regions of rbcL and rpoC1. In the phylogenetic analyses, all species of Asian origin showed clear divergence from Cucumis dipsaceus and Cucumis prophetarum, which were African in origin. Mukia maderaspatana and Dicaelospermum ritchiei showed very low evolutionary divergence and are reported close to each other. C. setosus had been confirmed as distinct species and C. callosus was found to be a wild progenitor of C. melo.

Evolutionary origin and status of two insect acetylcholinesterases and their structural conservation and differentiation.

Acetylcholinesterase (AChE) plays a pivotal role in synaptic transmission in the cholinergic nervous system of most animals, including insects. Insects possess duplicated AChE gene loci (ace1 vs. ace2) encoding two distinct AChEs (AChE1 and AChE2). A phylogenetic analysis suggested that the last common ancestor of two aces shared its origin with Platyhelminthes. In addition, the ace duplication event likely occurred after the divergence of Protostomian but before the split of Ecdysozoa. The ace1 lineage exhibited a significantly lower evolutionary rate (d and dN/dS ratio) than the ace2 lineage, suggesting that the ace1 lineage has retained the essential function of synaptic transmission following its duplication. Therefore, the putative functional transition from ace1 to ace2 observed in some Hymenopteran insects appears to be a local and relatively recent event. The amino acid sequence comparison and three-dimensional modeling of insect AChEs identified a few consistent differences in the amino acid residues in functionally crucial domains between two AChEs, which are likely responsible for the functional differentiation between two AChEs. A unique amino acid substitution causing a dramatic reduction in the catalytic activity of AChE1 in some Hymenopteran insects was suggested to be responsible for the aforementioned functional transition of ace.

Pediatric Aplastic Anemia and Refractory Cytopenia of Childhood: A Retrospective Single Institutional Analysis to Determine Outcomes and Histomorphological Predictors

IntroductionPediatric acquired aplastic anemia (AA) is a hypocellular bone marrow condition that is often difficult to distinguish from inherited bone marrow failure syndromes (IBMFS) and hypoplastic refractory cytopenia of childhood (RCC). RCC is a provisional entity for which the clinical implications are still under investigation. Historically, patients with RCC have been classified as AA. In this study, we sought to assess the intra-observer reproducibility and prognostic value of the histological criteria for RCC and AA as defined in the WHO classification. Specifically, we evaluated if RCC is an independent prognostic factor of overall survival (OS) and event-free survival (EFS), including treatment failure, disease progression and clonal evolution.MethodsWe performed a retrospective analysis of 149 AA patients seen at a single center between 1976-2010. Patients that met clinical or molecular diagnostic criteria for inherited bone marrow failure syndromes were excluded. We evaluated 5-year EFS, OS, and response rate to immunosuppressive therapy (IST); outcomes after matched HLA-identical related donor transplant (MRD) and matched unrelated donor (MUD) stem cell transplantation, as well as toxicities and clonal evolution. Of the 149 eligible individuals, 72 had diagnostic pathology material available for review. A double-blinded analysis of bone marrow aspirate and biopsy slides was undertaken by 3 pediatric hematopathologists. Each pathologist reviewed the slides of the entire study set and independently made a determination of the diagnosis. In cases where one or more differed in their assessment, the three conferred with an additional senior pediatric hematopathologist and all four reached agreement on a ‘consensus diagnosis’. To describe the degree of concordance between the assessments of the pathologists, a kappa coefficient was calculated. A logistic regression model was used to identify factors prognostic of treatment failure. Survival curves were generated using the methods of Kaplan and Meier.ResultsThe 149 patients were classified as moderate aplastic anemia (MAA) (n=58), severe aplastic anemia (SAA) (n=50) and very severe aplastic anemia (vSAA) (n=41). Ninety-one patients received IST, 50 underwent a MRD HSCT, and 8 were observed without treatment. The concordance between pathologists in the assessment of the diagnosis of AA or RCC was modest, but ultimately a consensus between the pathologists was reached. The overall EFS and OS were 50.8% and 73.1% for all patients. The 5-year OS and 5-year EFS for all patients receiving IST were 87.8% and 51.5%, respectively, with a failure to respond to IST in 48%. Patients with vSAA had worse 5-year OS compared to SAA and MAA patients, respectively (p=0.02). 5-year OS was comparable at 83.6%±7.2 and 85.3%±5.2 for patients receiving a MUD or MRD respectively. Within AA patients receiving IST, none of the following factors had prognostic value to predict failure of treatment: consensus diagnosis of RCC, macrocytosis (MCV > 100), or HgF% > 4%. An MCV >100and HgF% >4% likewise were not associated with consensus diagnosis of RCC. However, a significantly higher hemoglobin (Hgb) and absolute reticulocyte count was found in patients with RCC compared to AA. Surprisingly the diagnosis of RCC was associated with a trend towards improved 5- year OS (84.9% versus 72.5%) and 5-year EFS (71.3% versus 52.5%) compared to AA. Five patients (~3%) of the analytical cohort all with the clinical diagnosis of MAA experienced clonal evolution or disease progression. Interestingly, the clinical diagnosis of vSAA significantly correlated with the histologic appearance of AA, whereas SAA and MAA corresponded with RCC, strongly suggesting a correlation between lower disease severity as determined by peripheral counts and/or marrow cellularity and the diagnosis of RCC.ConclusionThe EFS and OS of the IST group in this single institution study is consistent with larger series. Our data indicate a low rate of clonal evolution in pediatric AA that in this series was associated exclusively with MAA. Most important, our findings suggest that the histologic diagnosis of RCC, reached by consensus among four pediatric hematopathologists does not predict disease outcome in this retrospective series of AA. These data indicate the need for larger prospective studies to determine the clinical significance of the classification. DisclosuresSartain:Hemostasis and Thrombosis Research Society: Research Funding.

Effect of hydrogen on the corrosion behavior of the Mg–xZn alloys

Abstract Hydrogen evolution reaction is inevitable during the corrosion of Mg alloys. The effect of hydrogen on the corrosion behavior of the Mg–2Zn and Mg–5Zn alloys is investigated by charging hydrogen treatment. The surface morphologies of the samples after charging hydrogen were observed using a scanning electron microscopy (SEM) and the corrosion resistance was evaluated by polarization curves. It is found that there are oxide films formed on the surface of the charged hydrogen samples. The low hydrogen evolution rate is helpful to improve the corrosion resistance of Mg alloys, while the high hydrogen evolution rate can increases the defects in the films and further deteriorates their protection ability. Also, the charging hydrogen effect is greatly associated with the microstructure of Mg substrate.

CPuORF correlates with miRNA responsive elements on protein evolutionary rates

miRNA is increasingly being recognized as a key regulator of metabolism in animals. A wealth of evidence has suggested that miRNA mainly binds 3′ UTR of mRNA and modulates the cell activities via repressing the mRNA translation. However, as the translation initiates at 5′ UTR, cis elements like upstream open reading frame (uORF) resided in 5′ UTR may also affect the translation efficiency or elongation. In this study, we performed a systematic analysis of miRNA responsive elements (MREs) and uORF of the same transcript in three model organisms (human, mouse, and Drosophila). Intriguingly, we found that the 3′ UTR length grew with the complexity of species (human>mouse>Drosophila), in sharp contrast with the invariability of 5′ UTR. Additionally, MRE number correlated well with the 3′ UTR length, while uORF number showed a weak correlation with the 5′ UTR length. Further, we found that human genes with conserved peptide upstream open reading frame (CPuORF) tend to have more MREs and lower evolutionary rates, which provides new insights into the correlation between UTR properties and translational control in animals.

The mitochondrial genome of Frankliniella intonsa: Insights into the evolution of mitochondrial genomes at lower taxonomic levels in Thysanoptera

Thrips is an ideal group for studying the evolution of mitochondrial (mt) genomes in the genus and family due to independent rearrangements within this order. The complete sequence of the mitochondrial DNA (mtDNA) of the flower thrips Frankliniella intonsa has been completed and annotated in this study. The circular genome is 15,215bp in length with an A+T content of 75.9% and contains the typical 37 genes and it has triplicate putative control regions. Nucleotide composition is A+T biased, and the majority of the protein-coding genes present opposite CG skew which is reflected by the nucleotide composition, codon and amino acid usage. Although the known thrips have massive gene rearrangements, it showed no reversal of strand asymmetry. Gene rearrangements have been found in the lower taxonomic levels of thrips. Three tRNA genes were translocated in the genus Frankliniella and eight tRNA genes in the family Thripidae. Although the gene arrangements of mt genomes of all three thrips species differ massively from the ancestral insect, they are all very similar to each other, indicating that there was a large rearrangement somewhere before the most recent common ancestor of these three species and very little genomic evolution or rearrangements after then. The extremely similar sequences among the CRs suggest that they are ongoing concerted evolution. Analyses of the up and downstream sequence of CRs reveal that the CR2 is actually the ancestral CR. The three CRs are in the same spot in each of the three thrips mt genomes which have the identical inverted genes. These characteristics might be obtained from the most recent common ancestor of this three thrips. Above observations suggest that the mt genomes of the three thrips keep a single massive rearrangement from the common ancestor and have low evolutionary rates among them.

An evolutionary perspective on leaf economics: phylogenetics of leaf mass per area in vascular plants.

In plant leaves, resource use follows a trade-off between rapid resource capture and conservative storage. This “worldwide leaf economics spectrum” consists of a suite of intercorrelated leaf traits, among which leaf mass per area, LMA, is one of the most fundamental as it indicates the cost of leaf construction and light-interception borne by plants. We conducted a broad-scale analysis of the evolutionary history of LMA across a large dataset of 5401 vascular plant species. The phylogenetic signal in LMA displayed low but significant conservatism, that is, leaf economics tended to be more similar among close relatives than expected by chance alone. Models of trait evolution indicated that LMA evolved under weak stabilizing selection. Moreover, results suggest that different optimal phenotypes evolved among large clades within which extremes tended to be selected against. Conservatism in LMA was strongly related to growth form, as were selection intensity and phenotypic evolutionary rates: woody plants showed higher conservatism in relation to stronger stabilizing selection and lower evolutionary rates compared to herbaceous taxa. The evolutionary history of LMA thus paints different evolutionary trajectories of vascular plant species across clades, revealing the coordination of leaf trait evolution with growth forms in response to varying selection regimes.

Studying tumorigenesis through network evolution and somatic mutational perturbations in the cancer interactome.

Cells govern biological functions through complex biological networks. Perturbations to networks may drive cells to new phenotypic states, for example, tumorigenesis. Identifying how genetic lesions perturb molecular networks is a fundamental challenge. This study used large-scale human interactome data to systematically explore the relationship among network topology, somatic mutation, evolutionary rate, and evolutionary origin of cancer genes. We found the unique network centrality of cancer proteins, which is largely independent of gene essentiality. Cancer genes likely have experienced a lower evolutionary rate and stronger purifying selection than those of noncancer, Mendelian disease, and orphan disease genes. Cancer proteins tend to have ancient histories, likely originated in early metazoan, although they are younger than proteins encoded by Mendelian disease genes, orphan disease genes, and essential genes. We found that the protein evolutionary origin (age) positively correlates with protein connectivity in the human interactome. Furthermore, we investigated the network-attacking perturbations due to somatic mutations identified from 3,268 tumors across 12 cancer types in The Cancer Genome Atlas. We observed a positive correlation between protein connectivity and the number of nonsynonymous somatic mutations, whereas a weaker or insignificant correlation between protein connectivity and the number of synonymous somatic mutations. These observations suggest that somatic mutational network-attacking perturbations to hub genes play an important role in tumor emergence and evolution. Collectively, this work has broad biomedical implications for both basic cancer biology and the development of personalized cancer therapy.