Low Evolutionary Rate Research Articles

The Genealogical Population Dynamics of HIV-1 in a Large Transmission Chain: Bridging within and among Host Evolutionary Rates

Transmission lies at the interface of human immunodeficiency virus type 1 (HIV-1) evolution within and among hosts and separates distinct selective pressures that impose differences in both the mode of diversification and the tempo of evolution. In the absence of comprehensive direct comparative analyses of the evolutionary processes at different biological scales, our understanding of how fast within-host HIV-1 evolutionary rates translate to lower rates at the between host level remains incomplete. Here, we address this by analyzing pol and env data from a large HIV-1 subtype C transmission chain for which both the timing and the direction is known for most transmission events. To this purpose, we develop a new transmission model in a Bayesian genealogical inference framework and demonstrate how to constrain the viral evolutionary history to be compatible with the transmission history while simultaneously inferring the within-host evolutionary and population dynamics. We show that accommodating a transmission bottleneck affords the best fit our data, but the sparse within-host HIV-1 sampling prevents accurate quantification of the concomitant loss in genetic diversity. We draw inference under the transmission model to estimate HIV-1 evolutionary rates among epidemiologically-related patients and demonstrate that they lie in between fast intra-host rates and lower rates among epidemiologically unrelated individuals infected with HIV subtype C. Using a new molecular clock approach, we quantify and find support for a lower evolutionary rate along branches that accommodate a transmission event or branches that represent the entire backbone of transmitted lineages in our transmission history. Finally, we recover the rate differences at the different biological scales for both synonymous and non-synonymous substitution rates, which is only compatible with the ‘store and retrieve’ hypothesis positing that viruses stored early in latently infected cells preferentially transmit or establish new infections upon reactivation.

Fast-evolving mitochondrial DNA in Ceriantharia: a reflection of hexacorallia paraphyly?

The low evolutionary rate of mitochondrial genes in Anthozoa has challenged their utility for phylogenetic and systematic purposes, especially for DNA barcoding. However, the evolutionary rate of Ceriantharia, one of the most enigmatic “orders” within Anthozoa, has never been specifically examined. In this study, the divergence of mitochondrial DNA of Ceriantharia was compared to members of other Anthozoa and Medusozoa groups. In addition, nuclear markers were used to check the relative phylogenetic position of Ceriantharia in relation to other Cnidaria members. The results demonstrated a pattern of divergence of mitochondrial DNA completely different from those estimated for other anthozoans, and phylogenetic analyses indicate that Ceriantharia is not included within hexacorallians in most performed analyses. Thus, we propose that the Ceriantharia should be addressed as a separate clade.

Rational design of the electrode morphology for oxygen evolution – enhancing the performance for catalytic water oxidation

The fundamental understanding of the electrode/electrolyte interface is of pivotal importance for the efficient electrochemical conversion and storage of electrical energy. However, the reasons for the low rate of electrocatalytic oxygen evolution and issues of long-term material stability, which are central constraints for attaining desirable efficiency for sustainable technologies like water electrolysis or electrochemical CO2 reduction, are still not completely resolved. While a lot of attention has been directed towards the search for new materials with unique (electro)catalytic properties, experimental results accumulated during the last four decades and prediction from models suggest that RuO2 possesses superior activity for oxygen evolution under acidic conditions. Considering that RuO2 is a material of choice, we show that tailoring the surface morphology on the meso- and macroscale has great potential for the improvement of the efficiency of this gas evolving reaction. Advanced analytical tools have been utilized for the combined investigation of both activity and stability. Namely, the potential dependent frequencies of gas-bubble evolution, an indicator for the activity of the electrode, were acquired by scanning electrochemical microscopy (SECM), while the dissolution of RuO2 was monitored using a micro electrochemical scanning flow cell combined with an inductively coupled plasma mass spectrometer (SFC-ICP-MS). The obtained fundamental insights will aid improving the design and thus performance of electrode materials for water oxidation.

Chloroplast DNA phylogeography of holy basil (Ocimum tenuiflorum) in Indian subcontinent.

Ocimum tenuiflorum L., holy basil “Tulsi”, is an important medicinal plant that is being grown and traditionally revered throughout Indian Subcontinent for thousands of years; however, DNA sequence-based genetic diversity of this aromatic herb is not yet known. In this report, we present our studies on the phylogeography of this species using trnL-trnF intergenic spacer of plastid genome as the DNA barcode for isolates from Indian subcontinent. Our pairwise distance analyses indicated that genetic heterogeneity of isolates remained quite low, with overall mean nucleotide p-distance of 5 × 10−4. However, our sensitive phylogenetic analysis using maximum likelihood framework was able to reveal subtle intraspecific molecular evolution of this species within the subcontinent. All isolates except that from North-Central India formed a distinct phylogenetic clade, notwithstanding low bootstrap support and collapse of the clade in Bayesian Inference. North-Central isolates occupied more basal position compared to other isolates, which is suggestive of its evolutionarily primitive status. Indian isolates formed a monophyletic and well-supported clade within O. tenuiflorum clade, which indicates a distinct haplotype. Given the vast geographical area of more than 3 million km2 encompassing many exclusive biogeographical and ecological zones, relatively low rate of evolution of this herb at this locus in India is particularly interesting.

Risk assessment of H2N2 influenza viruses from the avian reservoir.

H2N2 influenza A viruses were the cause of the 1957-1958 pandemic. Historical evidence demonstrates they arose from avian virus ancestors, and while the H2N2 subtype has disappeared from humans, it persists in wild and domestic birds. Reemergence of H2N2 in humans is a significant threat due to the absence of humoral immunity in individuals under the age of 50. Thus, examination of these viruses, particularly those from the avian reservoir, must be addressed through surveillance, characterization, and antiviral testing. The data presented here are a risk assessment of 22 avian H2N2 viruses isolated from wild and domestic birds over 6 decades. Our data show that they have a low rate of genetic and antigenic evolution and remained similar to isolates circulating near the time of the pandemic. Most isolates replicated in mice and human bronchial epithelial cells, but replication in swine tissues was low or absent. Multiple isolates replicated in ferrets, and 3 viruses were transmitted to direct-contact cage mates. Markers of mammalian adaptation in hemagglutinin (HA) and PB2 proteins were absent from all isolates, and they retained a preference for avian-like α2,3-linked sialic acid receptors. Most isolates remained antigenically similar to pandemic A/Singapore/1/57 (H2N2) virus, suggesting they could be controlled by the pandemic vaccine candidate. All viruses were susceptible to neuraminidase inhibitors and adamantanes. Nonetheless, the sustained pathogenicity of avian H2N2 viruses in multiple mammalian models elevates their risk potential for human infections and stresses the need for continual surveillance as a component of prepandemic planning.

Extraordinarily low evolutionary rates of short wavelength-sensitive opsin pseudogenes

Aquatic organisms such as cichlids, coelacanths, seals, and cetaceans are active in UV–blue color environments, but many of them mysteriously lost their abilities to detect these colors. The loss of these functions is a consequence of the pseudogenization of their short wavelength-sensitive (SWS1) opsin genes without gene duplication. We show that the SWS1 gene (BdenS1ψ) of the deep-sea fish, pearleye (Benthalbella dentata), became a pseudogene in a similar fashion about 130million years ago (Mya) yet it is still transcribed. The rates of nucleotide substitution (~1.4×10−9/site/year) of the pseudogenes of these aquatic species as well as some prosimian and bat species are much smaller than the previous estimates for the globin and immunoglobulin pseudogenes.

Brain transcriptome of the violet-eared waxbillUraeginthus granatinaand recent evolution in the songbird genome

Songbirds are important models for the study of social behaviour and communication. To complement the recent genome sequencing of the domesticated zebra finch, we sequenced the brain transcriptome of a closely related songbird species, the violet-eared waxbill (Uraeginthus granatina). Both the zebra finch and violet-eared waxbill are members of the family Estrildidae, but differ markedly in their social behaviour. Using Roche 454 RNA sequencing, we generated an assembly and annotation of 11 084 waxbill orthologues of 17 475 zebra finch genes (64%), with an average transcript length of 1555 bp. We also identified 5985 single nucleotide polymorphisms (SNPs) of potential utility for future population genomic studies. Comparing the two species, we found evidence for rapid protein evolution (ω) and low polymorphism of the avian Z sex chromosome, consistent with prior studies of more divergent avian species. An intriguing outlier was putative chromosome 4A, which showed a high density of SNPs and low evolutionary rate relative to other chromosomes. Genome-wide ω was identical in zebra finch and violet-eared waxbill lineages, suggesting a similar demographic history with efficient purifying natural selection. Further comparisons of these and other estrildid finches may provide insights into the evolutionary neurogenomics of social behaviour.

Yin and Yang of disease genes and death genes between reciprocally scale-free biological networks

Biological networks often show a scale-free topology with node degree following a power-law distribution. Lethal genes tend to form functional hubs, whereas non-lethal disease genes are located at the periphery. Uni-dimensional analyses, however, are flawed. We created and investigated two distinct scale-free networks; a protein–protein interaction (PPI) and a perturbation sensitivity network (PSN). The hubs of both networks exhibit a low molecular evolutionary rate (P < 8 × 10−12, P < 2 × 10−4) and a high codon adaptation index (P < 2 × 10−16, P < 2 × 10−8), indicating that both hubs have been shaped under high evolutionary selective pressure. Moreover, the topologies of PPI and PSN are inversely proportional: hubs of PPI tend to be located at the periphery of PSN and vice versa. PPI hubs are highly enriched with lethal genes but not with disease genes, whereas PSN hubs are highly enriched with disease genes and drug targets but not with lethal genes. PPI hub genes are enriched with essential cellular processes, but PSN hub genes are enriched with environmental interaction processes, having more TATA boxes and transcription factor binding sites. It is concluded that biological systems may balance internal growth signaling and external stress signaling by unifying the two opposite scale-free networks that are seemingly opposite to each other but work in concert between death and disease.

Twisted Signatures of GC-Biased Gene Conversion Embedded in an Evolutionary Stable Karyotype

The genomes of many vertebrates show a characteristic heterogeneous distribution of GC content, the so-called GC isochore structure. The origin of isochores has been explained via the mechanism of GC-biased gene conversion (gBGC). However, although the isochore structure is declining in many mammalian genomes, the heterogeneity in GC content is being reinforced in the avian genome. Despite this discrepancy, which remains unexplained, examinations of individual substitution frequencies in mammals and birds are both consistent with the gBGC model of isochore evolution. On the other hand, a negative correlation between substitution and recombination rate found in the chicken genome is inconsistent with the gBGC model. It should therefore be important to consider along with gBGC other consequences of recombination on the origin and fate of mutations, as well as to account for relationships between recombination rate and other genomic features. We therefore developed an analytical model to describe the substitution patterns found in the chicken genome, and further investigated the relationships between substitution patterns and several genomic features in a rigorous statistical framework. Our analysis indicates that GC content itself, either directly or indirectly via interrelations to other genomic features, has an impact on the substitution pattern. Further, we suggest that this phenomenon is particularly visible in avian genomes due to their unusually low rate of chromosomal evolution. Because of this, interrelations between GC content and other genomic features are being reinforced, and are as such more pronounced in avian genomes as compared with other vertebrate genomes with a less stable karyotype.

Why coelacanths are not ‘living fossils’

A series of recent studies on extant coelacanths has emphasised the slow rate of molecular and morphological evolution in these species. These studies were based on the assumption that a coelacanth is a 'living fossil' that has shown little morphological change since the Devonian, and they proposed a causal link between low molecular evolutionary rate and morphological stasis. Here, we have examined the available molecular and morphological data and show that: (i) low intra-specific molecular diversity does not imply low mutation rate, (ii) studies not showing low substitution rates in coelacanth are often neglected, (iii) the morphological stability of coelacanths is not supported by paleontological evidence. We recall that intra-species levels of molecular diversity, inter-species genome divergence rates and morphological divergence rates are under different constraints and they are not necessarily correlated. Finally, we emphasise that concepts such as 'living fossil', 'basal lineage', or 'primitive extant species' do not make sense from a tree-thinking perspective.

Membrane Environment Imposes Unique Selection Pressures on Transmembrane Domains of G Protein-Coupled Receptors

We have investigated the influence of the plasma membrane environment on the molecular evolution of G protein-coupled receptors (GPCRs), the largest receptor family in Metazoa. In particular, we have analyzed the site-specific rate variation across the two primary structural partitions, transmembrane (TM) and extramembrane (EM), of these membrane proteins. We find that TM domains evolve more slowly than do EM domains, though TM domains display increased rate heterogeneity relative to their EM counterparts. Although the majority of residues across GPCRs experience strong to weak purifying selection, many GPCRs experience positive selection at both TM and EM residues, albeit with a slight bias towards the EM. Further, a subset of GPCRs, chemosensory receptors (including olfactory and taste receptors), exhibit increased rates of evolution relative to other GPCRs, an effect which is more pronounced in their TM spans. Although it has been previously suggested that the TM's low evolutionary rate is caused by their high percentage of buried residues, we show that their attenuated rate seems to stem from the strong biophysical constraints of the membrane itself, or by functional requirements. In spite of the strong evolutionary constraints acting on the TM spans of GPCRs, positive selection and high levels of evolutionary rate variability are common. Thus, biophysical constraints should not be presumed to preclude a protein's ability to evolve.

Slow evolving satellite DNAs: the case of a centromeric satellite in Chalcides ocellatus (Forskål, 1775) (Reptilia, Scincidae)

Satellite DNAs represent a preponderant portion of eukaryotic genomes, and despite the ample literature on satDNAs of eukaryotes little is known about these repetitive elements in reptiles. Studies on reptiles satellite DNAs have been mainly focused on lacertid lizards and only one aimed at characterising these repetitive elements in skinks. Here, the isolation and characterisation of a satellite DNA in two populations of the ocellated skink, Chalcides ocellatus (Forskål, 1775), is presented. The repetitive element isolated is located at centromeres of all chromosomes of the complement, shows a tendency towards AT enrichment (53.5%), and contains short motifs that are common in centromeric satellites of eukaryotes (TG/CA, GAAA). The satellite shows an extremely low evolutionary rate (0.13% per million year) that make it unsuitable as a phylogenetic probe to assess the genetic differentiation of the populations investigated, that show a deep genetic divergence at mitochondrial level. The influence of satellite location on chromosomes and chromosomal morphology are invoked to explain this unusually slow mutation rate.

Genetic analysis of Newcastle disease virus from Punjab, Pakistan

The strains of Newcastle disease virus (NDV) were isolated from five suspected outbreaks of ND in broiler (n = 3) and layers (n = 2) poultry farms. The egg-isolated viruses were subjected to biological and genetic characterization. Based on the biological characterization, isolates showed haemagglutination titer ≥log 2(7), mean death time <55 h, intracerebral pathogenecity index ≤1.8, and egg lethal dose 50 from 10(-7.15) to 10(-9.31)/1 ml. Genetic characterization of the fusion (F) gene revealed that the isolates clustered with NDV strains of genotype VII (VIIf) within class II, which remained predominant genotype in the domestic poultry of Asia. The deduced amino acid sequence of the isolates confirmed virulent motif (112)RRQKRF(117) at the F protein cleavage site. A bioinformatics and pairwise comparison approach was applied to estimate the synonymous and non-synonymous substitution rates (dN/dS) and selective evolutionary pressure for the F protein. The dN/dS calculated for genotype VII indicate purifying selection, which resulted in a low evolution rate in F gene. The F protein shows a strong negative pressure throughout the length of the protein and no recombination event was determined. Collectively, the results suggest that very similar virulent strains of NDV are involved during current wave of disease outbreak throughout the country. From these results, in conjunction with our recent reports of NDV from Pakistan, it is possible to conclude that emergence of novel group may require revisiting the diagnostics and vaccine control strategies.

Insights into the Evolutionary Features of Human Neurodegenerative Diseases

Comparative analyses between human disease and non-disease genes are of great interest in understanding human disease gene evolution. However, the progression of neurodegenerative diseases (NDD) involving amyloid formation in specific brain regions is still unknown. Therefore, in this study, we mainly focused our analysis on the evolutionary features of human NDD genes with respect to non-disease genes. Here, we observed that human NDD genes are evolutionarily conserved relative to non-disease genes. To elucidate the conserved nature of NDD genes, we incorporated the evolutionary attributes like gene expression level, number of regulatory miRNAs, protein connectivity, intrinsic disorder content and relative aggregation propensity in our analysis. Our studies demonstrate that NDD genes have higher gene expression levels in favor of their lower evolutionary rates. Additionally, we observed that NDD genes have higher number of different regulatory miRNAs target sites and also have higher interaction partners than the non-disease genes. Moreover, miRNA targeted genes are known to have higher disorder content. In contrast, our analysis exclusively established that NDD genes have lower disorder content. In favor of our analysis, we found that NDD gene encoded proteins are enriched with multi interface hubs (party hubs) with lower disorder contents. Since, proteins with higher disorder content need to adapt special structure to reduce their aggregation propensity, NDD proteins found to have elevated relative aggregation propensity (RAP) in support of their lower disorder content. Finally, our categorical regression analysis confirmed the underlined relative dominance of protein connectivity, 3′UTR length, RAP, nature of hubs (singlish/multi interface) and disorder content for such evolutionary rates variation between human NDD genes and non-disease genes.

Analysis of the relationships between evolvability, thermodynamics, and the functions of intrinsically disordered proteins/regions

The evolvability of proteins is not only restricted by functional and structural importance, but also by other factors such as gene duplication, protein stability, and an organism's robustness. Recently, intrinsically disordered proteins (IDPs)/regions (IDRs) have been suggested to play a role in facilitating protein evolution. However, the mechanisms by which this occurs remain largely unknown. To address this, we have systematically analyzed the relationship between the evolvability, stability, and function of IDPs/IDRs. Evolutionary analysis shows that more recently emerged IDRs have higher evolutionary rates with more functional constraints relaxed (or experiencing more positive selection), and that this may have caused accelerated evolution in the flanking regions and in the whole protein. A systematic analysis of observed stability changes due to single amino acid mutations in IDRs and ordered regions shows that while most mutations induce a destabilizing effect in proteins, mutations in IDRs cause smaller stability changes than in ordered regions. The weaker impact of mutations in IDRs on protein stability may have advantages for protein evolvability in the gain of new functions. Interestingly, however, an analysis of functional motifs in the PROSITE and ELM databases showed that motifs in IDRs are more conserved, characterized by smaller entropy and lower evolutionary rate, than in ordered regions. This apparently opposing evolutionary effect may be partly due to the flexible nature of motifs in IDRs, which require some key amino acid residues to engage in tighter interactions with other molecules. Our study suggests that the unique conformational and thermodynamic characteristics of IDPs/IDRs play an important role in the evolvability of proteins to gain new functions.

Purifying selection modulates the estimates of population differentiation and confounds genome-wide comparisons across single-nucleotide polymorphisms.

An improved understanding of the biological and numerical properties of measures of population differentiation across loci is becoming increasingly more important because of their growing use in analyzing genome-wide polymorphism data for detecting population structures, inferring the rates of migration, and identifying local adaptations. In a genome-wide analysis, we discovered that the estimates of population differentiation (e.g., F(ST), θ, and Jost's D) calculated for human single-nucleotide polymorphisms (SNPs) are strongly and positively correlated to the position-specific evolutionary rates measured from multispecies alignments. That is, genomic positions (loci) experiencing higher purifying selection (lower evolutionary rates) produce lower values for the degree of population differentiation than those evolving with faster rates. We show that this pattern is completely mediated by the negative effects of purifying selection on the minor allele frequency (MAF) at individual loci. Our results suggest that inferences and methods relying on the comparison of population differentiation estimates (F(ST), θ, and Jost's D) based on SNPs across genomic positions should be restricted to loci with similar MAFs and/or the rates of evolution in genome scale surveys.

Analysis of Liriope spicata and Its Related Species Based on DNA Barcoding Technique

To discuss the potential of cpDNA trnL-F and psbA-trnH as DNA barcode of Liriope spicata(Thunberg) Loureiro and its related species,cpDNA trnL-F and psbA-trnH sequences were analysed.These two regions were respectively amplified by PCR and then purified and sequenced successfully.The results showed that the lengths of trnL-F sequences in 18 plant samples belonging to 9 species of liriopogons varied from 355 to 356 bp.There was no difference in the trnL-F of various species of liriope,but some specifically variable sites were found in this fragment,which led to the identification between Ophiopogon japonicus(Thunb.) Ker-Gawl and Ophiopogon bodinieri Levl.The length of psbA-trnH region was 543-544 bp,there were only some identification sites in O.japonicus(Thunb.) Ker-Gawl.Because of the low rate of evolution and the high conservation,these two cpDNA spacer regions could be only appropriate as a DNA barcode to identify liriopogons at generic level,but there is a degree of limit at lower taxonomic level.

The chemical‐speciation hypothesis in Liolaemus: a response to Pincheira‐Donoso

The chemical‐speciation hypothesis in <i><scp>L</scp>iolaemus</i>: a response to <scp>P</scp>incheira‐<scp>D</scp>onoso

Highly Variable Chloroplast Markers for Evaluating Plant Phylogeny at Low Taxonomic Levels and for DNA Barcoding

BackgroundAt present, plant molecular systematics and DNA barcoding techniques rely heavily on the use of chloroplast gene sequences. Because of the relatively low evolutionary rates of chloroplast genes, there are very few choices suitable for molecular studies on angiosperms at low taxonomic levels, and for DNA barcoding of species.Methodology/Principal FindingsWe scanned the entire chloroplast genomes of 12 genera to search for highly variable regions. The sequence data of 9 genera were from GenBank and 3 genera were of our own. We identified nearly 5% of the most variable loci from all variable loci in the chloroplast genomes of each genus, and then selected 23 loci that were present in at least three genera. The 23 loci included 4 coding regions, 2 introns, and 17 intergenic spacers. Of the 23 loci, the most variable (in order from highest variability to lowest) were intergenic regions ycf1-a, trnK, rpl32-trnL, and trnH-psbA, followed by trnSUGA-trnGUCC, petA-psbJ, rps16-trnQ, ndhC-trnV, ycf1-b, ndhF, rpoB-trnC, psbE-petL, and rbcL-accD. Three loci, trnSUGA-trnGUCC, trnT-psbD, and trnW-psaJ, showed very high nucleotide diversity per site (π values) across three genera. Other loci may have strong potential for resolving phylogenetic and species identification problems at the species level. The loci accD-psaI, rbcL-accD, rpl32-trnL, rps16-trnQ, and ycf1 are absent from some genera. To amplify and sequence the highly variable loci identified in this study, we designed primers from their conserved flanking regions. We tested the applicability of the primers to amplify target sequences in eight species representing basal angiosperms, monocots, eudicots, rosids, and asterids, and confirmed that the primers amplified the desired sequences of these species.Significance/ConclusionsChloroplast genome sequences contain regions that are highly variable. Such regions are the first consideration when screening the suitable loci to resolve closely related species or genera in phylogenetic analyses, and for DNA barcoding.

Theoretical Investigation of the Metal-Doped SrTiO3 Photocatalysts for Water Splitting

The effects of a series metal dopants on the photocatalytic activity of SrTiO3-based photocatalyst are investigated using first principle DFT calculations. The SrTiO3:Rh(1%) loaded with Pt has been found to give the best efficiency in water splitting. However, the same host doped with Ru leads to very low H2 evolution rate even it has a better visible light response. The analysis of the density of states and the calculated absorption spectra were used to illustrate the mechanisms that influence the photocatalytic efficiency. Our calculation results suggested that the two competing factors, the free electron generation (via light harvesting) and the charge recombination (due to the presence of recombination centers) process resulted in the existence of the optimal dopant concentration for the transition-metal-doped SrTiO3 lattice. The energy states introduced by dopant Rh in the bandgap of SrTiO3 were found to be very close to the valence band maximum. These new states thus reduce the bandgap of catalyst and enhance its light absorption capability. Furthermore, the proximity of these states to the valence band allows for efficient electron replenishment and thus reduces the probability of trapping electrons from the conduction band. In contrast, the energy states introduced by dopant Ru are significantly higher than the valence band making them an isolated recombination center. These Ru associated states also reduces the driving force for oxidation reaction. As a result, the Rh-doped SrTiO3 catalysts are found to provide a high H2 evolution rate.