ABSTRACT
As species diverge, a wide range of evolutionary processes lead to changes in protein-protein interaction (PPI) networks and metabolic networks. The rate at which molecular networks evolve is an important question in evolutionary biology. Previous empirical work has focused on interactomes from model organisms to calculate rewiring rates, but this is limited by the relatively small number of species and sparse nature of network data across species. We present a proxy for variation in network topology: variation in drug-drug interactions (DDIs), obtained by studying drug combinations (DCs) across taxa. Here, we propose the rate at which DDIs change across species as an estimate of the rate at which the underlying molecular network changes as species diverge. We computed the evolutionary rates of DDIs using previously published data from a high-throughput study in gram-negative bacteria. Using phylogenetic comparative methods, we found that DDIs diverge rapidly over short evolutionary time periods, but that divergence saturates over longer time periods. In parallel, we mapped drugs with known targets in PPI and cofunctional networks. We found that the targets of synergistic DDIs are closer in these networks than other types of DCs and that synergistic interactions have a higher evolutionary rate, meaning that nodes that are closer evolve at a faster rate. Future studies of network evolution may use DC data to gain larger-scale perspectives on the details of network evolution within and between species.
Subject(s)
Phylogeny , Evolution, Molecular , Protein Interaction Maps , Drug Interactions , Gram-Negative Bacteria/genetics , Biological Evolution , Metabolic Networks and PathwaysABSTRACT
There is now abundant evidence of rapid evolution in natural populations, but the genetic mechanisms of these changes remain unclear. One possible route to rapid evolution is through changes in the expression of genes that influence traits under selection. We examined contemporary evolutionary gene expression changes in plant populations responding to environmental fluctuations. We compared genome-wide gene expression, using RNA-seq, in two populations of Brassica rapa collected over four time points between 1997 and 2014, during which precipitation in southern California fluctuated dramatically and phenotypic and genotypic changes occurred. By combining transcriptome profiling with the resurrection approach, we directly examined evolutionary changes in gene expression over time. For both populations, we found a substantial number of differentially expressed genes between generations, indicating rapid evolution in the expression of many genes. Using existing gene annotations, we found that many changes occurred in genes involved in regulating stress responses and flowering time. These appeared related to the fluctuations in precipitation and were potentially adaptive. However, the evolutionary changes in gene expression differed across generations within and between populations, indicating largely independent evolutionary trajectories across populations and over time. Our study provides strong evidence for rapid evolution in gene expression, and indicates that changes in gene expression can be one mechanism of rapid evolutionary responses to selection episodes. This study also illustrates that combining resurrection studies with transcriptomics is a powerful approach for investigating evolutionary changes at the gene regulatory level, and will provide new insights into the genetic basis of contemporary evolution.
Subject(s)
Brassica rapa , Brassica rapa/genetics , Climate , Gene Expression , Gene Expression Profiling , PhenotypeABSTRACT
Whole-genome duplications (WGDs) are widespread and prevalent in vascular plants and frequently coincide with major episodes of global and climatic upheaval, including the mass extinction at the Cretaceous-Tertiary boundary (c. 65 Ma) and during more recent periods of global aridification in the Miocene (c. 10-5 Ma). Here, we explore WGDs in the diverse flowering plant clade Malpighiales. Using transcriptomes and complete genomes from 42 species, we applied a multipronged phylogenomic pipeline to identify, locate, and determine the age of WGDs in Malpighiales using three means of inference: distributions of synonymous substitutions per synonymous site (Ks ) among paralogs, phylogenomic (gene tree) reconciliation, and a likelihood-based gene-count method. We conservatively identify 22 ancient WGDs, widely distributed across Malpighiales subclades. Importantly, these events are clustered around the Eocene-Paleocene transition (c. 54 Ma), during which time the planet was warmer and wetter than any period in the Cenozoic. These results establish that the Eocene Climatic Optimum likely represents a previously unrecognized period of prolific WGDs in plants, and lends further support to the hypothesis that polyploidization promotes adaptation and enhances plant survival during episodes of global change, especially for tropical organisms like Malpighiales, which have tight thermal tolerances.
Subject(s)
Genome, Plant , Malpighiales/genetics , Phylogeny , Adaptation, Physiological , Climate , Likelihood Functions , Malpighiales/physiologyABSTRACT
The large amounts of transcriptome data available for Arabidopsis thaliana make a compelling case for the need to generalize results across studies and extract the most robust and meaningful information possible from them. The results of various studies seeking to identify water stress-responsive genes only partially overlap. The aim of this work was to combine transcriptomic studies in a systematic way that identifies commonalities in response, taking into account variation among studies due to batch effects as well as sampling variation, while also identifying the effect of study-specific variables, such as the method of applying water stress, and the part of the plant the mRNA was extracted from. We used meta-analysis, the quantitative synthesis of independent research results, to summarize expression responses to water stress across studies, and meta-regression to model the contribution of covariates that may affect gene expression. We found that some genes with small but consistent differential responses become evident only when results are synthesized across experiments, and are missed in individual studies. We also identified genes with expression responses that are attributable to use of different plant parts and alternative methods for inducing water stress. Our results indicate that meta-analysis and meta-regression provide a powerful approach for identifying a robust gene set that is less sensitive to idiosyncratic results and for quantifying study characteristics that result in contrasting gene expression responses across studies. Combining meta-analysis with individual analyses may contribute to a richer understanding of the biology of water stress responses, and may prove valuable in other gene expression studies.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/genetics , Gene Expression Regulation, Plant , Stress, Physiological , Transcriptome , Arabidopsis/physiology , Arabidopsis Proteins/genetics , Dehydration , Gene Expression Profiling , Plant Leaves/genetics , Plant Leaves/physiology , Plant Roots/genetics , Plant Roots/physiology , Plant Shoots/genetics , Plant Shoots/physiology , Regression AnalysisABSTRACT
There is increasing evidence that evolution can occur rapidly in response to selection. Recent advances in sequencing suggest the possibility of documenting genetic changes as they occur in populations, thus uncovering the genetic basis of evolution, particularly if samples are available from both before and after selection. Here, we had a unique opportunity to directly assess genetic changes in natural populations following an evolutionary response to a fluctuation in climate. We analysed genome-wide differences between ancestors and descendants of natural populations of Brassica rapa plants from two locations that rapidly evolved changes in multiple phenotypic traits, including flowering time, following a multiyear late-season drought in California. These ancestor-descendant comparisons revealed evolutionary shifts in allele frequencies in many genes. Some genes showing evolutionary shifts have functions related to drought stress and flowering time, consistent with an adaptive response to selection. Loci differentiated between ancestors and descendants (FST outliers) were generally different from those showing signatures of selection based on site frequency spectrum analysis (Tajima's D), indicating that the loci that evolved in response to the recent drought and those under historical selection were generally distinct. Very few genes showed similar evolutionary responses between two geographically distinct populations, suggesting independent genetic trajectories of evolution yielding parallel phenotypic changes. The results show that selection can result in rapid genome-wide evolutionary shifts in allele frequencies in natural populations, and highlight the usefulness of combining resurrection experiments in natural populations with genomics for studying the genetic basis of adaptive evolution.
Subject(s)
Brassica rapa/genetics , Droughts , Evolution, Molecular , Gene Pool , Selection, Genetic , Adaptation, Physiological/genetics , California , Gene Frequency , Genetics, Population , Genome, PlantABSTRACT
Recent studies have suggested that plant genomes have undergone potentially rampant horizontal gene transfer (HGT), especially in the mitochondrial genome. Parasitic plants have provided the strongest evidence of HGT, which appears to be facilitated by the intimate physical association between the parasites and their hosts. A recent phylogenomic study demonstrated that in the holoparasite Rafflesia cantleyi (Rafflesiaceae), whose close relatives possess the world's largest flowers, about 2.1% of nuclear gene transcripts were likely acquired from its obligate host. Here, we used next-generation sequencing to obtain the 38 protein-coding and ribosomal RNA genes common to the mitochondrial genomes of angiosperms from R. cantleyi and five additional species, including two of its closest relatives and two host species. Strikingly, our phylogenetic analyses conservatively indicate that 24%-41% of these gene sequences show evidence of HGT in Rafflesiaceae, depending on the species. Most of these transgenic sequences possess intact reading frames and are actively transcribed, indicating that they are potentially functional. Additionally, some of these transgenes maintain synteny with their donor and recipient lineages, suggesting that native genes have likely been displaced via homologous recombination. Our study is the first to comprehensively assess the magnitude of HGT in plants involving a genome (i.e., mitochondria) and a species interaction (i.e., parasitism) where it has been hypothesized to be potentially rampant. Our results establish for the first time that, although the magnitude of HGT involving nuclear genes is appreciable in these parasitic plants, HGT involving mitochondrial genes is substantially higher. This may represent a more general pattern for other parasitic plant clades and perhaps more broadly for angiosperms.
Subject(s)
Evolution, Molecular , Gene Transfer, Horizontal/genetics , Host-Parasite Interactions/genetics , Plants/genetics , DNA, Mitochondrial/genetics , Flowers/genetics , Genome, Mitochondrial , Genome, Plant , Phylogeny , Plants/parasitology , RNA, Ribosomal/genetics , SymbiosisABSTRACT
Upstream regulatory sequences that control gene expression evolve rapidly, yet the expression patterns and functions of most genes are typically conserved. To address this paradox, we have reconstructed computationally and resurrected in vivo the cis-regulatory regions of the ancestral Drosophila eve stripe 2 element and evaluated its evolution using a mathematical model of promoter function. Our feed-forward transcriptional model predicts gene expression patterns directly from enhancer sequence. We used this functional model along with phylogenetics to generate a set of possible ancestral eve stripe 2 sequences for the common ancestors of 1) D. simulans and D. sechellia; 2) D. melanogaster, D. simulans, and D. sechellia; and 3) D. erecta and D. yakuba. These ancestral sequences were synthesized and resurrected in vivo. Using a combination of quantitative and computational analysis, we find clear support for functional compensation between the binding sites for Bicoid, Giant, and Krüppel over the course of 40-60 My of Drosophila evolution. We show that this compensation is driven by a coupling interaction between Bicoid activation and repression at the anterior and posterior border necessary for proper placement of the anterior stripe 2 border. A multiplicity of mechanisms for binding site turnover exemplified by Bicoid, Giant, and Krüppel sites, explains how rapid sequence change may occur while maintaining the function of the cis-regulatory element.
Subject(s)
Drosophila melanogaster/genetics , Enhancer Elements, Genetic , Evolution, Molecular , Animals , Bayes Theorem , Binding Sites , Drosophila Proteins/genetics , Genes, Insect , Genetic Speciation , Homeodomain Proteins/genetics , Models, Genetic , Phylogeny , Transcription Factors/genetics , Transcription, GeneticABSTRACT
The molecular era has fundamentally reshaped our knowledge of the evolution and diversification of angiosperms. One outstanding question is the phylogenetic placement of Amborella trichopoda Baill., commonly thought to represent the first lineage of extant angiosperms. Here, we leverage publicly available data and provide a broad coalescent-based species tree estimation of 45 seed plants. By incorporating 310 nuclear genes, our coalescent analyses strongly support a clade containing Amborella plus water lilies (i.e., Nymphaeales) that is sister to all other angiosperms across different nucleotide rate partitions. Our results also show that commonly applied concatenation methods produce strongly supported, but incongruent placements of Amborella: slow-evolving nucleotide sites corroborate results from coalescent analyses, whereas fast-evolving sites place Amborella alone as the first lineage of extant angiosperms. We further explored the performance of coalescent versus concatenation methods using nucleotide sequences simulated on (i) the two alternate placements of Amborella with branch lengths and substitution model parameters estimated from each of the 310 nuclear genes and (ii) three hypothetical species trees that are topologically identical except with respect to the degree of deep coalescence and branch lengths. Our results collectively suggest that the Amborella alone placement inferred using concatenation methods is likely misled by fast-evolving sites. This appears to be exacerbated by the combination of long branches in stem group angiosperms, Amborella, and Nymphaeales with the short internal branch separating Amborella and Nymphaeales. In contrast, coalescent methods appear to be more robust to elevated substitution rates.
Subject(s)
Classification/methods , Magnoliopsida/classification , Nymphaea/classification , Phylogeny , Computer Simulation , Genes, Plant/genetics , Magnoliopsida/genetics , Nymphaea/genetics , Plastids/geneticsABSTRACT
Levels of gene expression show considerable variation in eukaryotes, but no fine-scale maps have been made of the fitness consequences of such variation in controlled genetic backgrounds and environments. To address this, we assayed fitness at many levels of up- and down-regulated expression of a single essential gene, LCB2, involved in sphingolipid synthesis in budding yeast Saccharomyces cerevisiae. Reduced LCB2 expression rapidly decreases cellular fitness, yet increased expression has little effect. The wild-type expression level is therefore perched on the edge of a nonlinear fitness cliff. LCB2 is upregulated when cells are exposed to osmotic stress; consistent with this, the entire fitness curve is shifted upward to higher expression under osmotic stress, illustrating the selective force behind gene regulation. Expression levels of LCB2 are lower in wild yeast strains than in the experimental lab strain, suggesting that higher levels in the lab strain may be idiosyncratic. Reports indicate that the effect sizes of alleles contributing to variation in complex phenotypes differ among environments and genetic backgrounds; our results suggest that such differences may be explained as simple shifts in the position of nonlinear fitness curves.
Subject(s)
Gene Expression Regulation, Fungal , Genetic Fitness , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Biological Evolution , Carrier Proteins/genetics , Carrier Proteins/metabolism , Environment , Protein Binding , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Serine C-Palmitoyltransferase/genetics , Serine C-Palmitoyltransferase/metabolismABSTRACT
Thraustochytrids (phylum: Labyrinthulomycota) are nonphotosynthetic marine protists. Some thraustochytrids have crtIBY, a trifunctional fusion gene encoding a protein capable of ß-carotene biosynthesis from geranylgeranyl pyrophosphate. Here we show that crtIBY is essential in, and encodes the sole pathway for, carotenoid biosynthesis in the thraustochytrid Aurantiochytrium limacinum ATCC MYA-1381. We explore the evolutionary origins of CrtIBY and discover that the closest related protein domains are present in a small but diverse group of other heterotrophic protists, including the apusomonad Thecamonas trahens and the dinoflagellates Oxyrrhis marina and Noctiluca scintillans. Each organism within this cluster also contains one or more ß-carotene 15-15' oxygenase genes (blh and rpe65), suggesting that the acquisition of ß-carotene biosynthesis genes may have been related to the production of retinal. Our findings support a novel origin of eukaryotic (apo)carotenoid biosynthesis by horizontal gene transfer from Actinobacteria, Bacteroidetes, and/or Archaea. This reveals a remarkable case of parallel evolution of eukaryotic (apo)carotenogenesis in divergent protistan lineages by repeated gene transfers.
Subject(s)
Carotenoids , Stramenopiles , beta Carotene/genetics , Gene Transfer, Horizontal , Bacteria/geneticsABSTRACT
Viruses are the most abundant biological entities in the world's oceans, where they play important ecological and biogeochemical roles. Metagenomics is revealing new groups of eukaryotic viruses, although disconnected from known hosts. Among these are the recently described mirusviruses, which share some similarities with herpesviruses.1 50 years ago, "herpes-type" viral particles2 were found in a thraustochytrid member of the labyrinthulomycetes, a diverse group of abundant and ecologically important marine eukaryotes,3,4 but could not be further characterized by methods then available. Long-read sequencing has allowed us to connect the biology of mirusviruses and thraustochytrids. We sequenced the genome of the genetically tractable model thraustochytrid Aurantiochytrium limacinum ATCC MYA-1381 and found that its 26 linear chromosomes have an extraordinary configuration. Subtelomeric ribosomal DNAs (rDNAs) found at all chromosome ends are interspersed with long repeated sequence elements denoted as long repeated-telomere and rDNA spacers (LORE-TEARS). We identified two genomic elements that are related to mirusvirus genomes. The first is a â¼300-kbp episome (circular element 1 [CE1]) present at a high copy number. Strikingly, the second, distinct, mirusvirus-like element is integrated between two sets of rDNAs and LORE-TEARS at the left end of chromosome 15 (LE-Chr15). Similar to metagenomically derived mirusviruses, these putative A. limacinum mirusviruses have a virion module related to that of herpesviruses along with an informational module related to nucleocytoplasmic large DNA viruses (NCLDVs). CE1 and LE-Chr15 bear striking similarities to episomal and endogenous latent forms of herpesviruses, respectively, and open new avenues of research into marine virus-host interactions.
Subject(s)
Viruses , DNA, Ribosomal , Genome , Heterochromatin , Eukaryota , Telomere , PhylogenyABSTRACT
BACKGROUND: Recent studies have shown that plant genomes have potentially undergone rampant horizontal gene transfer (HGT). In plant parasitic systems HGT appears to be facilitated by the intimate physical association between the parasite and its host. HGT in these systems has been invoked when a DNA sequence obtained from a parasite is placed phylogenetically very near to its host rather than with its closest relatives. Studies of HGT in parasitic plants have relied largely on the fortuitous discovery of gene phylogenies that indicate HGT, and no broad systematic search for HGT has been undertaken in parasitic systems where it is most expected to occur. RESULTS: We analyzed the transcriptomes of the holoparasite Rafflesia cantleyi Solms-Laubach and its obligate host Tetrastigma rafflesiae Miq. using phylogenomic approaches. Our analyses show that several dozen actively transcribed genes, most of which appear to be encoded in the nuclear genome, are likely of host origin. We also find that hundreds of vertically inherited genes (VGT) in this parasitic plant exhibit codon usage properties that are more similar to its host than to its closest relatives. CONCLUSIONS: Our results establish for the first time a substantive number of HGTs in a plant host-parasite system. The elevated rate of unidirectional host-to- parasite gene transfer raises the possibility that HGTs may provide a fitness benefit to Rafflesia for maintaining these genes. Finally, a similar convergence in codon usage of VGTs has been shown in microbes with high HGT rates, which may help to explain the increase of HGTs in these parasitic plants.
Subject(s)
Gene Transfer, Horizontal/genetics , Magnoliopsida/genetics , Codon/genetics , DNA, Plant/genetics , Host-Parasite Interactions/genetics , Magnoliopsida/classification , Magnoliopsida/parasitology , Phylogeny , Transcriptome/geneticsABSTRACT
Common fragile sites (CFSs) represent large, highly unstable regions of the human genome. CFS sequences are sensitive to perturbation of replication; however, the molecular basis for the instability at CFSs is poorly understood. We hypothesized that a unique epigenetic pattern may underlie the unusual sensitivity of CFSs to replication interference. To examine this hypothesis, we analyzed chromatin modification patterns within the six human CFSs with the highest levels of breakage, and their surrounding non-fragile regions (NCFSs). Chromatin at most of the CFSs analyzed has significantly less histone acetylation than that of their surrounding NCFSs. Trichostatin A and/or 5-azadeoxycytidine treatment reduced chromosome breakage at CFSs. Furthermore, chromatin at the most commonly expressed CFS, the FRA3B, is more resistant to micrococcal nuclease than that of the flanking non-fragile sequences. These results demonstrate that histone hypoacetylation is a characteristic epigenetic pattern of CFSs, and chromatin within CFSs might be relatively more compact than that of the NCFSs, indicating a role for chromatin conformation in genomic instability at CFSs. Moreover, lack of histone acetylation at CFSs may contribute to the defective response to replication stress characteristic of CFSs, leading to the genetic instability characteristic of this regions.
Subject(s)
Chromosome Fragile Sites , Genome, Human , Histones/metabolism , Acetylation , Cell Line , Chromatin/genetics , Chromatin/metabolism , Epigenesis, Genetic , Female , Genomic Instability , Histones/genetics , HumansABSTRACT
BACKGROUND: Pathogens are key components in natural and agricultural plant systems. There is evidence of evolutionary changes in disease susceptibility as a consequence of climate change, but we know little about the underlying genetic basis of this evolution. To address this, we took advantage of a historical seed collection of a Brassica rapa population, which we previously demonstrated evolved an increase in disease susceptibility to a necrotrophic fungal pathogen following a drought. RESULTS: Previously, we combined a resurrection experiment with genome-wide sequencing of 124 pooled ancestral and descendant plants. Here, using these previously generated sequence data (Franks et al. in Mol Ecol 25(15):3622-3631, 2016), we show that well-characterized necrotrophic fungal pathogen response (NFPR) genes have evolved, as indicated by changes in allele frequency, between ancestors and descendants, with several of them identified as extreme FST outliers. The jasmonic acid (JA) signaling pathway in particular seems to underlie the evolution of disease susceptibility, in addition to its well characterized role in plastic disease response. We identify a list of 260 genes that are both NFPR genes and are differentially expressed in response to drought, based on publicly available data. We present evidence that five of these genes evolved between ancestors and descendants, suggesting that the drought acted as the evolutionary driver, and that the accompanying increase in disease susceptibility may have been a consequence of genetic pleiotropy. CONCLUSIONS: Our study provides evidence that for this population, standing variation in NFPR genes is affected by natural selection related to climate change. Our results reveal potentially important candidates that may underlie trait evolution in both crops and natural systems. Additionally, this trade-off between adaptation to biotic and abiotic stresses is an example of how climate change can have diverse and unexpected consequences.
Subject(s)
Brassica rapa , Droughts , Acclimatization , Adaptation, Physiological/genetics , Brassica rapa/genetics , Disease SusceptibilityABSTRACT
BACKGROUND: Determining an absolute timescale for avian evolutionary history has proven contentious. The two sources of information available, paleontological data and inference from extant molecular genetic sequences (colloquially, 'rocks' and 'clocks'), have appeared irreconcilable; the fossil record supports a Cenozoic origin for most modern lineages, whereas molecular genetic estimates suggest that these same lineages originated deep within the Cretaceous and survived the K-Pg (Cretaceous-Paleogene; formerly Cretaceous-Tertiary or K-T) mass-extinction event. These two sources of data therefore appear to support fundamentally different models of avian evolution. The paradox has been speculated to reflect deficiencies in the fossil record, unrecognized biases in the treatment of genetic data or both. Here we attempt to explore uncertainty and limit bias entering into molecular divergence time estimates through: (i) improved taxon (n = 135) and character (n = 4594 bp mtDNA) sampling; (ii) inclusion of multiple cladistically tested internal fossil calibration points (n = 18); (iii) correction for lineage-specific rate heterogeneity using a variety of methods (n = 5); (iv) accommodation of uncertainty in tree topology; and (v) testing for possible effects of episodic evolution. RESULTS: The various 'relaxed clock' methods all indicate that the major (basal) lineages of modern birds originated deep within the Cretaceous, although temporal intraordinal diversification patterns differ across methods. We find that topological uncertainty had a systematic but minor influence on date estimates for the origins of major clades, and Bayesian analyses assuming fixed topologies deliver similar results to analyses with unconstrained topologies. We also find that, contrary to expectation, rates of substitution are not autocorrelated across the tree in an ancestor-descendent fashion. Finally, we find no signature of episodic molecular evolution related to either speciation events or the K-Pg boundary that could systematically mislead inferences from genetic data. CONCLUSION: The 'rock-clock' gap has been interpreted by some to be a result of the vagaries of molecular genetic divergence time estimates. However, despite measures to explore different forms of uncertainty in several key parameters, we fail to reconcile molecular genetic divergence time estimates with dates taken from the fossil record; instead, we find strong support for an ancient origin of modern bird lineages, with many extant orders and families arising in the mid-Cretaceous, consistent with previous molecular estimates. Although there is ample room for improvement on both sides of the 'rock-clock' divide (e.g. accounting for 'ghost' lineages in the fossil record and developing more realistic models of rate evolution for molecular genetic sequences), the consistent and conspicuous disagreement between these two sources of data more likely reflects a genuine difference between estimated ages of (i) stem-group origins and (ii) crown-group morphological diversifications, respectively. Further progress on this problem will benefit from greater communication between paleontologists and molecular phylogeneticists in accounting for error in avian lineage age estimates.
Subject(s)
Birds/genetics , DNA, Mitochondrial/genetics , Evolution, Molecular , Fossils , Genetic Speciation , Animals , Bayes Theorem , Birds/classification , Genetic Variation , PhylogenyABSTRACT
Marine protists are a polyphyletic group of organisms playing major roles in the ecology and biogeochemistry of the oceans, including performing much of Earth's photosynthesis and driving the carbon, nitrogen, and silicon cycles. In addition, marine protists occupy key positions in the tree of life, including as the closest relatives of metazoans. Despite all the reasons to better understand them, knowledge of the cell biology of most marine protist lineages is sparse. This is beginning to change thanks to vibrant growth in the development of new model organisms. Here, we survey some recent advances in studying the cell biology of marine protists toward understanding the functional basis of their unique features, gaining new perspectives on universal eukaryotic biology, and for understanding homologous biology within metazoans and the evolution of metazoan traits.
Subject(s)
Eukaryota/physiology , Marine Biology , Plankton , Animals , Biological Evolution , Eukaryota/geneticsABSTRACT
ATP-competitive kinase inhibitors often bind several kinases due to the high conservation of the ATP binding pocket. Through clustering analysis of a large kinome profiling dataset, we found a cluster of eight promiscuous kinases that on average bind more than five times more kinase inhibitors than the other 398 kinases in the dataset. To understand the structural basis of promiscuous inhibitor binding, we determined the co-crystal structure of the receptor tyrosine kinase DDR1 with the type I inhibitors dasatinib and VX-680. Surprisingly, we find that DDR1 binds these type I inhibitors in an inactive conformation typically reserved for type II inhibitors. Our computational and biochemical studies show that DDR1 is unusually stable in this inactive conformation, giving a mechanistic explanation for inhibitor promiscuity. This phenotypic clustering analysis provides a strategy to obtain functional insights not available by sequence comparison alone.
Subject(s)
Discoidin Domain Receptor 1/antagonists & inhibitors , Protein Kinase Inhibitors/chemistry , Amino Acid Sequence , Binding Sites , Cluster Analysis , Dasatinib/chemistry , Dasatinib/metabolism , Discoidin Domain Receptor 1/genetics , Discoidin Domain Receptor 1/metabolism , Humans , Molecular Dynamics Simulation , Mutagenesis , Piperazines/chemistry , Piperazines/metabolism , Protein Binding , Protein Kinase Inhibitors/metabolism , Protein Kinases/chemistry , Protein Kinases/metabolism , Protein Structure, Tertiary , Sequence AlignmentABSTRACT
Recent studies have demonstrated adaptive evolutionary responses to climate change, but little is known about how these responses may influence ecological interactions with other organisms, including natural enemies. We used a resurrection experiment in the greenhouse to examine the effect of evolutionary responses to drought on the susceptibility of Brassica rapa plants to a fungal pathogen, Alternaria brassicae. In agreement with previous studies in this population, we found an evolutionary shift to earlier flowering postdrought, which was previously shown to be adaptive. Here, we report the novel finding that postdrought descendant plants were also more susceptible to disease, indicating a rapid evolutionary shift to increased susceptibility. This was accompanied by an evolutionary shift to increased specific leaf area (thinner leaves) following drought. We found that flowering time and disease susceptibility displayed plastic responses to experimental drought treatments, but that this plasticity did not match the direction of evolution, indicating that plastic and evolutionary responses to changes in climate can be opposed. The observed evolutionary shift to increased disease susceptibility accompanying adaptation to drought provides evidence that even if populations can rapidly adapt in response to climate change, evolution in other traits may have ecological effects that could make species more vulnerable.
Subject(s)
Alternaria/physiology , Brassica rapa/microbiology , Droughts , Plant Diseases/microbiology , Acclimatization , Biological Evolution , Brassica rapa/physiology , Climate Change , Host-Pathogen InteractionsABSTRACT
The sudden appearance and potential lethality of severe acute respiratory syndrome associated coronavirus (SARS-CoV) in humans has focused attention on understanding its origins. Here, we assess phylogenetic relationships for the SARS-CoV lineage as well as the history of host-species shifts for SARS-CoV and other coronaviruses. We used a Bayesian phylogenetic inference approach with sliding window analyses of three SARS-CoV proteins: RNA dependent RNA polymerase (RDRP), nucleocapsid (N) and spike (S). Conservation of RDRP allowed us to use a set of Arteriviridae taxa to root the Coronaviridae phylogeny. We found strong evidence for a recombination breakpoint within SARS-CoV RDRP, based on different, well supported trees for a 5' fragment (supporting SARS-CoV as sister to a clade including all other coronaviruses) and a 3' fragment (supporting SARS-CoV as sister to group three avian coronaviruses). These different topologies are statistically significant: the optimal 5' tree could be rejected for the 3' region, and the optimal 3' tree could be rejected for the 5' region. We did not find statistical evidence for recombination in analyses of N and S, as there is little signal to differentiate among alternative trees. Comparison of phylogenetic trees for 11 known host-species and 36 coronaviruses, representing coronavirus groups 1-3 and SARS-CoV, based on N showed statistical incongruence indicating multiple host-species shifts for coronaviruses. Inference of host-species associations is highly sensitive to sampling and must be considered cautiously. However, current sampling suggests host-species shifts between mouse and rat, chicken and turkey, mammals and manx shearwater, and humans and other mammals. The sister relationship between avian coronaviruses and the 3' RDRP fragment of SARS-CoV suggests an additional host-species shift. Demonstration of recombination in the SARS-CoV lineage indicates its potential for rapid unpredictable change, a potentially important challenge for public health management and for drug and vaccine development.
Subject(s)
Host-Parasite Interactions/physiology , RNA-Dependent RNA Polymerase/genetics , Recombination, Genetic , Severe acute respiratory syndrome-related coronavirus/physiology , Animals , Bayes Theorem , Coronavirus/physiology , Humans , Membrane Glycoproteins/genetics , Nucleocapsid/genetics , Phylogeny , Severe acute respiratory syndrome-related coronavirus/genetics , Spike Glycoprotein, Coronavirus , Viral Envelope Proteins/geneticsABSTRACT
Nine proteins have been assigned to date to the superfamily of mammalian small heat shock proteins (sHsps): Hsp27 (HspB1, Hsp25), myotonic dystrophy protein kinase-binding protein (MKBP) (HspB2), HspB3, alphaA-crystallin (HspB4), alphaB-crystallin (HspB5), Hsp20 (p20, HspB6), cardiovascular heat shock protein (cvHsp [HspB7]), Hsp22 (HspB8), and HspB9. The most pronounced structural feature of sHsps is the alpha-crystallin domain, a conserved stretch of approximately 80 amino acid residues in the C-terminal half of the molecule. Using the alpha-crystallin domain of human Hsp27 as query in a BLAST search, we found sequence similarity with another mammalian protein, the sperm outer dense fiber protein (ODFP). ODFP occurs exclusively in the axoneme of sperm cells. Multiple alignment of human ODFP with the other human sHsps reveals that the primary structure of ODFP fits into the sequence pattern that is typical for this protein superfamily: alpha-crystallin domain (conserved), N-terminal domain (less conserved), central region (variable), and C-terminal tails (variable). In a phylogenetic analysis of 167 proteins of the sHsp superfamily, using Bayesian inference, mammalian ODFPs form a clade and are nested within previously identified sHsps, some of which have been implicated in cytoskeletal functions. Both the multiple alignment and the phylogeny suggest that ODFP is the 10th member of the superfamily of mammalian sHsps, and we propose to name it HspB10 in analogy with the other sHsps. The C-terminal tail of HspB10 has a remarkable low-complexity structure consisting of 10 repeats of the motif C-X-P. A BLAST search using the C-terminal tail as query revealed similarity with sequence elements in a number of Drosophila male sperm proteins, and mammalian type I keratins and cornifin-alpha. Taken together, the following findings suggest a specialized role of HspB10 in cytoskeleton: (1) the exclusive location in sperm cell tails, (2) the phylogenetic relationship with sHsps implicated in cytoskeletal functions, and (3) the partial similarity with cytoskeletal proteins.