Potential Positive Selection Research Articles

Some mitochondrial genes perform better for damselfly phylogenetics: species‐ and population‐level analyses of four complete mitogenomes of Euphaea sibling species

AbstractAnimal mitochondrial genes continue to provide an efficient and inexpensive assessment of genetic diversity. However, which mitochondrial genes should be selected to best estimate species phylogeny and population genealogy remains uncertain for most under‐sampled taxa. We analysed four complete mitochondrial genomes of sibling species of Euphaea damselflies, E. decorata, E. ornata, E. formosa and E. yayeyamana (Insecta, Odonata, Euphaeidae), to examine the patterns of selection and to evaluate the phylogenetic utility of the mitochondrial genes compared with nuclear genes. The results indicated that mitochondrial protein‐coding nad2 (NADH dehydrogenase subunit 2) and noncoding A + T‐rich (control region) genes have the highest mutation rates and more phylogenetic utility [higher parsimony‐informative sites; higher α (the shape parameter of gamma distribution); lower rates of heterogeneity among sites; and higher relative substitution rates] than all the other mitochondrial and nuclear genes analysed. In contrast, the animal DNA barcoding gene cytochrome c oxidase subunit 1 (cox1) had average values for all estimated parameters of phylogenetic performance and was sometimes outperformed by other mitochondrial genes. The majority of the mitochondrial and nuclear genes in Euphaea damselflies have experienced frequent purifying selection, except for two cases of potential positive selection in NADH dehydrogenase subunit 3 (nad3) and elongation factor 1α (EF1α), and all mitochondrial genes had experienced stronger purifying selection than nuclear genes. Our findings indicated that mitochondrial nad2 and the A + T‐rich region should be selected to provide efficient and high‐resolution phylogenetic markers for damselflies at the species and population level.

Divergent evolution of Di-lysine ER retention vs. farnesylation motif-mediated anchoring of the AnkB virulence effector to the Legionella-containing vacuolar membrane

Within macrophages and amoeba, the Legionella-containing vacuole (LCV) membrane is derived from the ER. The bona fide F-box AnkB effector protein of L. pneumophila strain AA100/130b is anchored to the cytosolic side of the LCV membrane through host-mediated farnesylation of its C-terminal eukaryotic “CaaX” motif. Here we show that the AnkB homologue of the Paris strain has a frame shift mutation that led to a loss of the CaaX motif and a concurrent generation of a unique C-terminal KNKYAP motif, which resembles the eukaryotic di-lysine ER-retention motif (KxKxx). Our phylogenetic analyses indicate that environmental isolates of L. pneumophila have a potential positive selection for the ER-retention KNKYAP motif. The AnkB-Paris effector is localized to the LCV membrane most likely through the ER-retention motif. Its ectopic expression in HEK293T cells localizes it to the perinuclear ER region and it trans-rescues the ankB mutant of strain AA100/130b in intra-vacuolar replication. The di-lysine ER retention motif of AnkB-Paris is indispensable for function; most likely as an ER retention motif that enables anchoring to the ER-derived LCV membrane. Our findings show divergent evolution of the ankB allele in exploiting either host farnesylation or the ER retention motif to be anchored into the LCV membrane.

Adaptive evolution of the rbcL gene in the genus Rheum (Polygonaceae)

ABSTRACTRapid putative radiations of Rheum might be caused by the recent uplifts of the Qinghai–Tibetan Plateau and the quaternary climate oscillations. To better understand the molecular adaptation associated with Rheum radiation, in this study, the adaptive evolution of the chloroplast rbcL gene was analysed using the Phylogenetic Analysis Program. The results showed that two amino acid residues (75F, 203I) were under positive selection. The spatial analysis indicated that the site (75F) was located in the β-sheet of the N-terminal loops involved in subunit interactions in the L8S8 molecule, and the site (203I) was in the α/β-barrel active centre located on the C-terminal domain of the large subunit of Rubisco. These results suggest that potential positive selection in rbcL might have played an important role in the adaption of Rheum species to the extreme environments in Qinghai–Tibetan Plateau regions, and different species lineages might have been subjected to different selective pressures.

Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission.

Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human.

Enterovirus D68 Infections Associated with Severe Respiratory Illness in Elderly Patients and Emergence of a Novel Clade in Hong Kong.

Despite the recent emergence of enterovirus D68 (EV-D68), its clinical impact on adult population is less well defined. To better define the epidemiology of EV-D68, 6,800 nasopharyngeal aspirates (NPAs) from 2010–2014 were subject to EV-D68 detection by RT-PCR and sequencing of 5′UTR and partial VP1. EV-D68 was detected in 30 (0.44%) NPAs from 22 children and 8 adults/elderlies. Sixteen patients (including five elderly) (53%) had pneumonia and 13 (43%) patients were complicated by small airway disease exacerbation. Phylogenetic analysis of VP1, 2C and 3D regions showed four distinct lineages of EV-D68, clade A1, A2, B1 and B3, with adults/elderlies exclusively infected by clade A2. The potentially new clade, B3, has emerged in 2014, while strains closely related to recently emerged B1 strains in the United States were also detected as early as 2011 in Hong Kong. The four lineages possessed distinct aa sequence patterns in BC and DE loops. Amino acid residues 97 and 140, within BC and DE-surface loops of VP1 respectively, were under potential positive selection. EV-D68 infections in Hong Kong usually peak in spring/summer, though with a delayed autumn/winter peak in 2011. This report suggests that EV-D68 may cause severe respiratory illness in adults/elderlies with underlying co-morbidities.

Evolution of the PEBP gene family and selective signature on FT‐like clade

AbstractThe PEBP family of proteins, which encode a phosphatidyl ethanolamine‐binding protein (PEBP) domain, serve as a hub in the network of integrating environmental and developmental signals to regulate flowering in all angiosperms. To understand how PEBP duplication genes arose and evolved during plant evolution, we identified 259 genes involved in the PEBP domain from 25 species, including angiosperms, gymnosperms, and embryophytes. We found that plant PEBP genes could be divided into three monophyletic groups, including FT‐like, TFL‐like and MFT‐like subgroups. Based on the phylogeny, FT‐like and TFL‐like subgroups split before the angiosperm divergence. The likelihood ratio test indicates that the FT‐like clade is significantly different in Ka/Ks with TFL‐like and MFT‐like clades. We found this shift in mutation might be attributed to the positive selection imposed on the fourth exon of recent FT duplications. Divergent expression patterns of FT paralogs indicated that they had undergone subfunctionalization after duplication. In addition, some of the FT‐like genes have been targets of selection during domestication in rice and maize, for which the flowering time is an important agronomic trait. These results imply potential recent positive selection on FT‐like genes with potential to increase the prevalence of novel functional alleles leading to extensive plant flowering time diversity and adaptation to environmental changes.

Adaptive Molecular Evolution of PHYE in Primulina, a Karst Cave Plant.

Limestone Karst areas possess high levels of biodiversity and endemism. Primulina is a typical component of Karst endemic floras. The high species richness and wide distribution in various Karst microenvironments make the genus an idea model for studying speciation and local adaptation. In this study, we obtained 10 full-length sequences of the phytochrome PHYE from available transcriptome resources of Primulina and amplified partial sequences of PHYE from the genomic DNA of 74 Primulina species. Then, we used maximum-likelihood approaches to explore molecular evolution of PHYE in this Karst cave plant. The results showed that PHYE was dominated by purifying selection in both data sets, and two sites were identified as potentially under positive selection. Furthermore, the ω ratio varies greatly among different functional domains of PHYE and among different species lineages. These results suggest that potential positive selection in PHYE might have played an important role in the adaption of Primulina to heterogeneous light environments in Karst regions, and different species lineages might have been subjected to different selective pressures.

Molecular variation in AVP and AVPR1a in New World monkeys (Primates, Platyrrhini): evolution and implications for social monogamy.

The neurohypophysial hormone arginine vasopressin (AVP) plays important roles in fluid regulation and vascular resistance. Differences in AVP receptor expression, particularly mediated through variation in the noncoding promoter region of the primary receptor for AVP (AVPR1a), may play a role in social phenotypes, particularly social monogamy, in rodents and humans. Among primates, social monogamy is rare, but is common among New World monkeys (NWM). AVP is a nonapeptide and generally conserved among eutherian mammals, although a recent paper demonstrated that some NWM species possess a novel form of the related neuropeptide hormone, oxytocin. We therefore characterized variation in the AVP and AVPR1a genes in 22 species representing every genus in the three major platyrrhine families (Cebidae, Atelidae and Pitheciidae). For AVP, a total of 16 synonymous substitutions were detected in 15 NWM species. No non-synonymous substitutions were noted, hence, AVP is conserved in NWM. By contrast, relative to the human AVPR1a, 66 predicted amino acids (AA) substitutions were identified in NWM. The AVPR1a N-terminus (ligand binding domain), third intracellular (G-protein binding domain), and C-terminus were variable among species. Complex evolution of AVPR1a is also apparent in NWM. A molecular phylogenetic tree inferred from AVPR1a coding sequences revealed some consensus taxonomic separation by families, but also a mixed group composed of genera from all three families. The overall dN/dS ratio of AVPR1a was 0.11, but signals of positive selection in distinct AVPR1a regions were observed, including the N-terminus, in which we identified six potential positive selection sites. AA substitutions at positions 241, 319, 399 and 409 occurred uniquely in marmosets and tamarins. Our results enhance the appreciation of genetic diversity in the mammalian AVP/AVPR1a system, and set the stage for molecular modeling of the neurohypophyseal hormones and social behavior in primates.

Molecular evolution of the sulphite efflux gene SSU1 in Saccharomyces cerevisiae

The SSU1 gene encoding a membrane sulfite pump is a main facilitator invovled in sulfite efflux. In Saccharomyce cerevisiae, various range of resistance to sulfite was observed among strains. To explore the evolution traits of SSU1 gene, the population data of S. cerevisiae were collected and analyzed. The phylogenetic analysis indicated that S. cerevisiae population can be classified into three sub-populations, and the positive selection was detected in population by McDonald-Kreitman test. The anaylsis of Ka/Ks ratios further showed that S. cerevisiae sub-population was undergoing positive selection. This finding was also supported by PAML branch model. Nine potential positive selection sites were predicted by branch-site model, and four sites exclusively belong to the sub-population under positive seletion. The data from ssulp protein structure demonstrated that three sites are substitutions between polar and hydrophobic amino acids, and only one site of substitutaion from basic amino acid to basic amino acid (345R/K). Because amino acid pKa values are crucial for sulfite pump to maintain their routine function, positive selection of these amino acid substitutions might affect sulfite efflux efficient.

Small Ancestry Informative Marker panels for complete classification between the original four HapMap populations

A protocol for the identification of Ancestry Informative Markers (AIMs) from genome-wide Single Nucleotide Polymorphism (SNP) data is proposed. The protocol consists of three main steps: identification of potential positive selection regions via F(ST) extremity measurement, SNP screening via two-stage attribute selection and classification model construction using a Naïve Bayes classifier. The two-stage attribute selection is composed of a newly developed round robin Symmetrical Uncertainty (SU) ranking technique and a wrapper embedded with a Naïve Bayes classifier. The protocol has been applied to the HapMap Phase II data. Two AIM panels, which consist of 10 and 16 SNPs that lead to complete classification between CEU, CHB, JPT and YRI populations, are identified. Moreover, the panels are at least four times smaller than those reported in previous studies. The results suggest that the protocol could be useful in a scenario involving a larger number of populations.

D N / d S does not show positive selection drives separation of polar‐tropical SAR11 populations

Mol Syst Biol. 8: 625 Large‐scale sequencing of environmental microorganisms (including genomes, metagenomes, and metatranscriptomes) now allows researchers to apply sequence‐based evolutionary genetics approaches to microbial ecology questions, including studying how microbes adapt to a diversity of natural environments. There is, however, a danger for misapplication and misinterpretation if the caveats and limitations of these evolutionary methods are not fully appreciated. Here, we highlight an example of such problems in an evolutionary analysis of potential positive selection within strains of SAR11 marine bacteria (Brown et al , 2012). We feel that these issues deserve wider recognition, particularly as evolutionary approaches become more widespread among environmental microbiologists. In the vast majority of genes, the ratio (ω) of non‐synonymous substitutions per non‐synonymous site ( d N ) to synonymous substitutions per synonymous site ( d S ) is 1, then this may be indicative of positive selection favoring amino‐acid replacements (Hughes and Nei, 1988, Hughes, 1999). If ω is not statistically different from 1, then there is evidence for neither purifying nor positive selection. Positive selection is not the only factor that can cause ω to be >1; since ω is a ratio, an unusually high ω value may indicate either an unusually high d N or an unusually low d S . For example, purifying selection on synonymous mutations can lead to a low d S and thus high ω (Parmley and Hurst, 2007). Approaches for calculating d S and d N can be classified into two categories, based on whether the underlying nucleotide evolutionary model takes into account the base/codon frequency bias (Supplementary Table S1; Zhang et al , 2006). For instance, the Yang and Nielsen method (YN00) considers the base/codon …

Differential expression of stem cell markers in human follicular bulge and interfollicular epidermal compartments

Although skin contains a number of stem cell repositories, their characterization has been hindered by a lack of specific markers and an unclear in vivo localization. In this study, we whole mounted single human scalp hair follicles and examined their profiles using in situ immunohistochemistry and multicolor immunofluorescence in search of markers to distinguish between stem cells residing in the interfollicular epidermis (IFE) and bulge. Our study revealed that expression of several biomarkers localized uniquely to the basal IFE (CD34 and CD117), bulge region (CD200), or both (CK15, CD49f, and CD29). In addition, we found that both basal IFE and bulge stem cells did not express CD71 or CD24 suggesting their potential utility as negative selection markers. Dermal papilla but not basal IFE or bulge stem cells expressed CD90, making it a potential positive selection marker for dermal hair follicle stem cells. The markers tested in this study may enable pursuit of cell sorting and purification strategies aimed at determining each stem cell population's unique molecular signature.

Delicious poison: genetics of Drosophila host plant preference

Insects use chemical cues to identify host plants, which suggests that chemosensory perception could be a target of natural selection during host specialization. Five papers using data from the 12 recently sequenced Drosophila genomes examined chemosensory gene function and evolution across specialist and generalist species. A functional study identifies odorant binding proteins that mediate loss of toxin avoidance in a specialist, and targeted genomic studies indicate specialists and island endemics lose chemosensory genes more rapidly than generalist and mainland relatives. Together, these studies suggest a mode of chemoreceptor evolution dominated by birth/death dynamics, coupled with a low level of potential positive selection.

Evidence for Positive Darwinian Selection of Vip Gene in Bacillus thuringiensis

Vegetative insecticidal proteins (VIPs), produced during the vegetative stage of their growth in Bacillus thuringiensis, are a group of insecticidal proteins and represent the second generation of insecticidal trans-genes that will complement the novel d-endotoxins in future. Fewer structural and functional relationships of Vip proteins are known in comparison with those of d-endotoxins. In this study, both the maximum-likelihood methods and the maximum parsimony based sliding window analysis were used to evaluate the molecular evolution of Vip proteins. As a result, strong evidence was found that Vip proteins are subject to the high rates of positive selection, and 16 sites are identified to be under positive selection using the Bayes Empirical Bayesian method. Interestingly, all these positively selected sites are located from site-705 to site-809 in the C-terminus of the Vip proteins. Most of these sites are exposed and clustered in the loop regions when mapped onto its computational predicted secondary tertiary and a part of the tertiary structure. It has been postulated that the high divergence in the C-terminal of Vip proteins may not result from the lack of functional constraints, but rather from the rapid mutation to adapt their targeted insects, driven by positive selection. The potential positive selection pressures may be an attempt to adapt for the “arm race” between Vip proteins and the targeted insects, or to enlarge their target's host range. Sites identified to be under positive selection may be related to the insect host range, which may shed a light on the investigation of the Vip proteins’ structural and functional relationships.

Salvage surgical resection after high-dose ifosfamide (HDIF) based regimens in advanced soft tissue sarcoma (ASTS): a potential positive selection bias--a study of the Spanish group for research on sarcomas (GEIS).

To assess the impact of different factors on response rate (RR), time to tumor progression (TTP), and overall survival time (OS) in patients with locally advanced or metastatic soft tissue sarcoma (ASTS), included in three protocols with high-dose ifosfamide (HDIF). One hundred fifty six ASTS patients included in three consecutive phase II trials with HDIF (>10 g/m(2)), alone or in combination with doxorubicin (DX), were analyzed. Cofactors were institution, trial, gender, age, performance status, histologic type, grade of malignancy, prior radiotherapy, presence of locoregional disease, metastatic site, salvage surgery, number of organs involved, and disease-free interval. By multivariate analysis performance status >0 and lack of salvage surgery correlated with a poorer survival. A good-risk and a poor-risk group were identified, with median survival time (OS) of 29, 5, and 10 months, respectively (P = 0.00001). The 1-, 2-, and 3-year OS for 83 good-risk patients (either with PS = 0 or receiving salvage surgery) was 83, 44, and 29%, respectively, those figures being 37, 7, and 3% for 73 poor-risk patients. The design of randomized trials in ASTS including HDIF should consider those prognostic factors as stratification variables.