scholarly journals Pathway Evolution by Horizontal Transfer and Positive Selection Is Accommodated by Relaxed Negative Selection upon Upstream Pathway Genes in Purple Bacterial Carotenoid Biosynthesis

2009 ◽  
Vol 191 (24) ◽  
pp. 7500-7508 ◽  
Author(s):  
Jonathan L. Klassen
Keyword(s):  
Positive Selection ◽  
Horizontal Transfer ◽  
Negative Selection ◽  
Biosynthetic Pathway ◽  
Carotenoid Biosynthesis ◽  
Biochemical Network ◽  
Biosynthetic Genes ◽  
Substrate Specificities ◽  
Functional Changes ◽  
Synonymous Mutations

ABSTRACT Horizontal gene transfer and selection are major forces driving microbial evolution. However, interactions between them are rarely studied. Phylogenetic analyses of purple bacterial carotenoid biosynthesis genes suggest two lineages: one producing spheroidenone and the other producing spirilloxanthin. Of the latter lineage, Rubrivivax gelatinosus S1 and Hoeflea phototrophica DFL-43 also or instead produce spheroidenone. Evolution of the spheroidenone pathway from that producing spirilloxanthin theoretically requires changes in the substrate specificity of upstream pathway enzymes and acquisition of a terminal ketolase (CrtA). In R. gelatinosus and likely also in H. phototrophica, CrtA was acquired from the Bacteroidetes, in which it functions as a hydroxylase. Estimation of nonsynonymous and synonymous mutations using several pairwise methods indicated positive selection upon both genes, consistent with their functional changes from hydroxylases to ketolases. Relaxed negative selection upon all other carotenoid biosynthetic genes in these organisms was also apparent, likely facilitating changes in their substrate specificities. Furthermore, all genes responsible for terminal carotenoid biosynthetic pathway steps were under reduced negative selection compared to those known to govern biosynthetic pathway specificity. Horizontal transfer of crtA into R. gelatinosus and H. phototrophica has therefore likely been promoted by (i) the apparent selective advantage of spheroidenone production relative to spirilloxanthin production, (ii) reduced negative selection upon other carotenoid biosynthetic genes, facilitating changes in their substrate specificities, and (iii) preexisting low enzyme substrate specificities due to relaxed negative selection. These results highlight the importance and complexity of selection acting upon both a horizontally transferred gene and the biochemical network into which it is integrating.

scholarly journals A Tetratricopeptide Repeat Protein Regulates Carotenoid Biosynthesis and Chromoplast Development in Monkeyflowers (Mimulus)

2017 ◽  
Author(s):  
Lauren E. Stanley ◽  
Baoqing Ding ◽  
Wei Sun ◽  
Fengjuan Mou ◽  
Connor Hill ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Anthocyanin Biosynthesis ◽  
Carotenoid Biosynthesis ◽  
Chemical Mutagenesis ◽  
Developmental Genetics ◽  
Tetratricopeptide Repeat ◽  
Loss Of Function ◽  
In Planta ◽  
Biosynthetic Genes ◽  
Carotenoid Biosynthetic Pathway

ABSTRACTThe incredible diversity of floral color and pattern in nature is largely determined by the transcriptional regulation of anthocyanin and carotenoid biosynthetic genes. While the transcriptional control of anthocyanin biosynthesis is well understood, little is known about the factors regulating the carotenoid biosynthetic pathway in flowers. Here, we characterize the Reduced Carotenoid Pigmentation 2 (RCP2) locus from two monkeyflower (Mimulus) species, the bumblebee-pollinated M. lewisii and hummingbird-pollinated M. verbenaceus. We show that loss-of-function mutations of RCP2 cause drastic down-regulation of the entire carotenoid biosynthetic pathway in these species. Through bulk segregant analysis and transgenic experiments, we have identified the causal gene underlying RCP2, encoding a tetratricopeptide repeat (TPR) protein that is closely related to the Arabidopsis Reduced Chloroplast Coverage (REC) proteins. RCP2 appears to regulate carotenoid biosynthesis independently of RCP1, a previously identified R2R3-MYB master regulator of carotenoid biosynthesis. We show that RCP2 is required for chromoplast development and suggest that it most likely regulates the expression of carotenoid biosynthetic genes through chromoplast-to-nucleus retrograde signaling. Furthermore, we demonstrate that M. verbenaceus is just as amenable to chemical mutagenesis and in planta transformation as the more extensively studied M. lewisii, making these two species an excellent platform for comparative developmental genetics studies of two closely related species with dramatic phenotypic divergence.

scholarly journals Genetic Characterization of the Carotenoid Biosynthetic Pathway in Methylobacterium extorquens AM1 and Isolation of a Colorless Mutant

2003 ◽  
Vol 69 (12) ◽  
pp. 7563-7566 ◽  
Author(s):  
Stephen J. Van Dien ◽  
Christopher J. Marx ◽  
Brooke N. O'Brien ◽  
Mary E. Lidstrom
Keyword(s):  
Biosynthetic Pathway ◽  
Genetic Characterization ◽  
Carotenoid Biosynthesis ◽  
Biosynthesis Pathway ◽  
Wild Type ◽  
Methylobacterium Extorquens ◽  
Growth Properties ◽  
Carotenoid Biosynthesis Pathway ◽  
Free Strain

ABSTRACT Genomic searches were used to reconstruct the putative carotenoid biosynthesis pathway in the pink-pigmented facultative methylotroph Methylobacterium extorquens AM1. Four genes for putative phytoene desaturases were identified. A colorless mutant was obtained by transposon mutagenesis, and the insertion was shown to be in one of the putative phytoene desaturase genes. Mutations in the other three did not affect color. The tetracycline marker was removed from the original transposon mutant, resulting in a pigment-free strain with wild-type growth properties useful as a tool for future experiments.

scholarly journals Genetic Diversity and Natural Selection of Plasmodium vivax Duffy Binding Protein-II From China-Myanmar Border of Yunnan Province, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Tian-Qi Shi ◽  
Hai-Mo Shen ◽  
Shen-Bo Chen ◽  
Kokouvi Kassegne ◽  
Yan-Bing Cui ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Population Structure ◽  
Natural Selection ◽  
Genetic Differentiation ◽  
Positive Selection ◽  
Plasmodium Vivax ◽  
Yunnan Province ◽  
Duffy Binding Protein ◽  
Synonymous Mutations ◽  
Selection Of

Malaria incidence has declined dramatically over the past decade and China was certified malaria-free in 2021. However, the presence of malaria in border areas and the importation of cases of malaria parasites are major challenges for the consolidation of the achievements made by China. Plasmodium vivax Duffy binding protein (PvDBP) performs a significant role in erythrocyte invasion, and is considered a promising P. vivax vaccine. However, the highly polymorphic region of PvDBP (PvDBP-II) impedes the development of blood-stage vaccine against P. vivax. In this study, we investigated the genetic diversity and natural selection of PvDBP-II among 124 P. vivax isolates collected from the China-Myanmar border (CMB) in Yunnan Province, China, during 2009–2011. To compare genetic diversity, natural selection, and population structure with CMB isolates, 85 pvdbp-II sequences of eastern Myanmar isolates were obtained from GenBank. In addition, global sequences of pvdbp-II were retrieved from GenBank to establish genetic differentiation relationships and networks with the CMB isolates. In total, 22 single nucleotide polymorphisms reflected in 20 non-synonymous and two synonymous mutations were identified. The overall nucleotide diversity of PvDBP-II from the 124 CMB isolates was 0.0059 with 21 haplotypes identified (Hd = 0.91). The high ratio of non-synonymous to synonymous mutations suggests that PvDBP-II had evolved under positive selection. Population structure analysis of the CMB and eastern Myanmar isolates were optimally grouped into five sub-populations (K = 5). Polymorphisms of PvDBP-II display that CMB isolates were genetically diverse. Mutation, recombination, and positive selection promote polymorphism of PvDBP-II of P. vivax population. Although low-level genetic differentiation in eastern Myanmar was identified along with the more effective malaria control measures, the complexity of population structure in malaria parasites has maintained. In conclusion, findings from this study advance knowledge of the understanding of the dynamic of P. vivax population, which will contribute to guiding the rational design of a PvDBP-II based vaccine.

scholarly journals Background Selection Does Not Mimic the Patterns of Genetic Diversity Produced by Selective Sweeps

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 499-519 ◽  
Author(s):  
Daniel R. Schrider
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Negative Selection ◽  
False Negative ◽  
False Negative Rate ◽  
Spatial Arrangement ◽  
Background Selection ◽  
Noncoding Dna ◽  
Protein Coding ◽  
Beneficial Allele

It is increasingly evident that natural selection plays a prominent role in shaping patterns of diversity across the genome. The most commonly studied modes of natural selection are positive selection and negative selection, which refer to directional selection for and against derived mutations, respectively. Positive selection can result in hitchhiking events, in which a beneficial allele rapidly replaces all others in the population, creating a valley of diversity around the selected site along with characteristic skews in allele frequencies and linkage disequilibrium among linked neutral polymorphisms. Similarly, negative selection reduces variation not only at selected sites but also at linked sites, a phenomenon called background selection (BGS). Thus, discriminating between these two forces may be difficult, and one might expect efforts to detect hitchhiking to produce an excess of false positives in regions affected by BGS. Here, we examine the similarity between BGS and hitchhiking models via simulation. First, we show that BGS may somewhat resemble hitchhiking in simplistic scenarios in which a region constrained by negative selection is flanked by large stretches of unconstrained sites, echoing previous results. However, this scenario does not mirror the actual spatial arrangement of selected sites across the genome. By performing forward simulations under more realistic scenarios of BGS, modeling the locations of protein-coding and conserved noncoding DNA in real genomes, we show that the spatial patterns of variation produced by BGS rarely mimic those of hitchhiking events. Indeed, BGS is not substantially more likely than neutrality to produce false signatures of hitchhiking. This holds for simulations modeled after both humans and Drosophila, and for several different demographic histories. These results demonstrate that appropriately designed scans for hitchhiking need not consider BGS’s impact on false-positive rates. However, we do find evidence that BGS increases the false-negative rate for hitchhiking, an observation that demands further investigation.

scholarly journals Developmental Regulation of the Expression of Amaryllidaceae Alkaloid Biosynthetic Genes in Narcissus papyraceus

Genes ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 594 ◽  
Author(s):  
Tarun Hotchandani ◽  
Justine de Villers ◽  
Isabel Desgagné-Penix
Keyword(s):  
Gene Expression ◽  
Heterocyclic Compounds ◽  
Biosynthetic Pathway ◽  
Developmental Stages ◽  
Developmental Regulation ◽  
Biological Effects ◽  
Biosynthetic Genes ◽  
Amaryllidaceae Alkaloids ◽  
Different Parts ◽  
Gene Expression Levels

Amaryllidaceae alkaloids (AAs) have multiple biological effects, which are of interest to the pharmaceutical industry. To unleash the potential of Amaryllidaceae plants as pharmaceutical crops and as sources of AAs, a thorough understanding of the AA biosynthetic pathway is needed. However, only few enzymes in the pathway are known. Here, we report the transcriptome of AA-producing paperwhites (Narcissus papyraceus Ker Gawl). We present a list of 21 genes putatively encoding enzymes involved in AA biosynthesis. Next, a cDNA library was created from 24 different samples of different parts at various developmental stages of N. papyraceus. The expression of AA biosynthetic genes was analyzed in each sample using RT-qPCR. In addition, the alkaloid content of each sample was analyzed by HPLC. Leaves and flowers were found to have the highest abundance of heterocyclic compounds, whereas the bulb, the lowest. Lycorine was also the predominant AA. The gene expression results were compared with the heterocyclic compound profiles for each sample. In some samples, a positive correlation was observed between the gene expression levels and the amount of compounds accumulated. However, due to a probable transport of enzymes and alkaloids in the plant, a negative correlation was also observed, particularly at stage 2.

scholarly journals Detecting Signatures of Positive Selection against a Backdrop of Compensatory Processes

2020 ◽  
Vol 37 (11) ◽  
pp. 3353-3362
Author(s):  
Peter B Chi ◽  
Westin M Kosater ◽  
David A Liberles
Keyword(s):  
Amino Acids ◽  
Statistical Model ◽  
Positive Selection ◽  
Traditional Method ◽  
3D Structure ◽  
Evolutionary Time ◽  
Synonymous Substitutions ◽  
Synonymous Mutations ◽  
Parametric Bootstrapping

Abstract There are known limitations in methods of detecting positive selection. Common methods do not enable differentiation between positive selection and compensatory covariation, a major limitation. Further, the traditional method of calculating the ratio of nonsynonymous to synonymous substitutions (dN/dS) does not take into account the 3D structure of biomacromolecules nor differences between amino acids. It also does not account for saturation of synonymous mutations (dS) over long evolutionary time that renders codon-based methods ineffective for older divergences. This work aims to address these shortcomings for detecting positive selection through the development of a statistical model that examines clusters of substitutions in clusters of variable radii. Additionally, it uses a parametric bootstrapping approach to differentiate positive selection from compensatory processes. A previously reported case of positive selection in the leptin protein of primates was reexamined using this methodology.

scholarly journals Positive and negative selection invoke distinct signaling pathways.

1996 ◽  
Vol 184 (1) ◽  
pp. 9-18 ◽  
Author(s):  
J Alberola-Ila ◽  
K A Hogquist ◽  
K A Swan ◽  
M J Bevan ◽  
R M Perlmutter
Keyword(s):  
T Cell ◽  
Positive Selection ◽  
Negative Selection ◽  
Mapk Pathway ◽  
Cell Receptor ◽  
Dominant Negative ◽  
Mapk Cascade ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

During T cell development, interaction of the T cell receptor (TCR) with cognate ligands in the thymus may result in either maturation (positive selection) or death (negative selection). The intracellular pathways that control these opposed outcomes are not well characterized. We have generated mice expressing dominant-negative Ras (dnRas) and Mek-1 (dMek) transgenes simultaneously, either in otherwise normal animals, or in animals expressing a transgenic TCR, thereby permitting a comprehensive analysis of peptide-specific selection. In this system, thymocyte maturation beyond the CD4+8+ stage is blocked almost completely, whereas negative selection, assessed using an in vitro deletion protocol, is quantitatively intact. This suggests that activation of the mitogen-activated protein kinase (MAPK) cascade is necessary for positive selection, but irrelevant for negative selection. Generation of gamma/delta and of CD4-8- alpha/beta T cells proceeds normally despite blockade of the MAPK cascade. Hence, only cells that mature via conventional, TCR-mediated repertoire selection require activation of the MAPK pathway to complete their maturation.

Changes in Bone Marrow Plasma Cell Surface Markers Following CD138-Magnetic Bead Based Positive Selection.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3516-3516
Author(s):  
Teresa K. Kimlinger ◽  
S. Vincent Rajkumar ◽  
Michael P. Kline ◽  
Jessica L. Haug ◽  
Michael M. Timm ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Positive Selection ◽  
Plasma Cell ◽  
Negative Selection ◽  
Plasma Cells ◽  
Cell Types ◽  
Magnetic Bead ◽  
The Other ◽  
Activation Markers ◽  
Cell Markers

Abstract Background: Isolation of malignant plasma cells from bone marrow of patients with monoclonal gammopathies is critical for studies into the disease biology. The isolation of plasma cells have generally been performed by positive selection using plasma cell markers such as CD138 or by negative selection by removing other marrow cells using a cocktail of antibodies. We have previously demonstrated differences in apoptotic rates in plasma cells with and without this enrichment step. Here we have examined the effect of CD138 magnetic bead selection on the surface phenotype of plasma cells by flow cytometry. Methods: Bone marrow aspirates from patients with myeloma (n=12) were first washed, and then lysed with ACK to eliminate red cells. The samples were split with a portion of the cells further processed for CD138 selection. ACK lysed only whole bone marrow (WBM) and sorted cells were stained with CD38, CD45, CD56, activation markers CD71 and CD69, adhesion markers CD49d, CD11b, and CD66, B cell markers CD19 and CD20, and clonality (kappa and lambda). Gates were drawn around the plasma cells and plasma cell subsets on the basis of CD38/45 expression for both sorted and unsorted samples. In addition, an aliquot of the sorted preparation was examined by immunohistochemistry to calculate the purity of the sorted sample. Results: Significant differences were observed in terms of the percentage of plasma cells expressing the different antigens when the cells were selected using CD138. This difference included a greater than 10% difference in expression between the two preparations as well as a change from positive to negative in several cases. There was a substantial loss in the expression of CD20, CD71 and CD11b on plasma cells following CD138 based sorting (Table). Among the other markers, CD49d remains unchanged and changes are variable for the other markers. In addition, in 8 of the 12 cases, there was a nearly complete loss of the CD45 positive subset with a loss of discrimination between CD45 negative and CD45 positive plasma cell subsets in the remaining CD138 sorted preparations (figure: unsorted left, sorted right). Conclusion: In conclusion, the process of CD138 sorting of plasma cells appears to change important markers on the plasma cells and may even eliminate a key subset from further analysis. This should be kept in mind when isolating plasma cells using CD138 positive selection for analysis such as gene expression profiling. Consideration should be given to negative selection using antibodies against other cell types to deplete them. Marker Unsorted % Sorted % CD56 74 67 CD69 11 2 CD71 23 8 CD49d 95 92 CD11b 33 4 CD66 5 1 CD20 16 6 Figure Figure

scholarly journals Extreme C-terminal sites are posttranslocationally glycosylated by the STT3B isoform of the OST

2013 ◽  
Vol 201 (1) ◽  
pp. 81-95 ◽  
Author(s):  
Shiteshu Shrimal ◽  
Steven F. Trueman ◽  
Reid Gilmore
Keyword(s):  
Endoplasmic Reticulum ◽  
Positive Selection ◽  
Protein C ◽  
Negative Selection ◽  
Bioinformatics Analysis ◽  
Chain Termination ◽  
Catalytic Subunits ◽  
C Terminus ◽  
Glycosylation Sites ◽  
Selection Of

Metazoan organisms assemble two isoforms of the oligosaccharyltransferase (OST) that have different catalytic subunits (STT3A or STT3B) and partially nonoverlapping roles in asparagine-linked glycosylation. The STT3A isoform of the OST is primarily responsible for co-translational glycosylation of the nascent polypeptide as it enters the lumen of the endoplasmic reticulum. The C-terminal 65–75 residues of a glycoprotein will not contact the translocation channel–associated STT3A isoform of the OST complex before chain termination. Biosynthetic pulse labeling of five human glycoproteins showed that extreme C-terminal glycosylation sites were modified by an STT3B-dependent posttranslocational mechanism. The boundary for STT3B-dependent glycosylation of C-terminal sites was determined to fall between 50 and 55 residues from the C terminus of a protein. C-terminal NXT sites were glycosylated more rapidly and efficiently than C-terminal NXS sites. Bioinformatics analysis of glycopeptide databases from metazoan organisms revealed a lower density of C-terminal acceptor sites in glycoproteins because of reduced positive selection of NXT sites and negative selection of NXS sites.

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