Fixation Of Amino Acids Research Articles

Evolution under a model of functionally buffered deleterious mutations can lead to positive selection in protein-coding genes.

Selective pressures on DNA sequences often result in departures from neutral evolution that can be captured by the McDonald-Kreitman (MK) test. However, the nature of such selective forces often remains unknown to experimentalists. Amino acid fixations driven by natural selection in protein-coding genes are commonly associated with a genetic arms race or changing biological purposes, leading to proteins with new functionality. Here, we evaluate the expectations of population genetic patterns under a buffering mechanism driving selective amino acids to fixation, which is motivated by an observed phenotypic rescue of otherwise deleterious nonsynonymous substitutions at bag of marbles (bam) and Sex lethal (Sxl) in Drosophila melanogaster. These two genes were shown to experience strong episodic bursts of natural selection potentially due to infections of the endosymbiotic bacteria Wolbachia observed among multiple Drosophila species. Using simulations to implement and evaluate the evolutionary dynamics of a Wolbachia buffering model, we demonstrate that selectively fixed amino acid replacements will occur, but that the proportion of adaptive amino acid fixations and the statistical power of the MK test to detect the departure from an equilibrium neutral model are both significantly lower than seen for an arms race/change-in-function model that favors proteins with diversified amino acids. We find that the observed selection pattern at bam in a natural population of D. melanogaster is more consistent with an arms race model than with the buffering model.

Functional Divergence of the bag-of-marbles Gene in the Drosophila melanogaster Species Group.

In Drosophila melanogaster, a key germline stem cell (GSC) differentiation factor, bag of marbles (bam) shows rapid bursts of amino acid fixations between sibling species D. melanogaster and Drosophila simulans, but not in the outgroup species Drosophila ananassae. Here, we test the null hypothesis that bam’s differentiation function is conserved between D. melanogaster and four additional Drosophila species in the melanogaster species group spanning approximately 30 million years of divergence. Surprisingly, we demonstrate that bam is not necessary for oogenesis or spermatogenesis in Drosophila teissieri nor is bam necessary for spermatogenesis in D. ananassae. Remarkably bam function may change on a relatively short time scale. We further report tests of neutral sequence evolution at bam in additional species of Drosophila and find a positive, but not perfect, correlation between evidence for positive selection at bam and its essential role in GSC regulation and fertility for both males and females. Further characterization of bam function in more divergent lineages will be necessary to distinguish between bam’s critical gametogenesis role being newly derived in D. melanogaster, D. simulans, Drosophila yakuba, and D. ananassae females or it being basal to the genus and subsequently lost in numerous lineages.

Chemical cross-linking on gelatin-hyaluronan loaded with hinokitiol for the preparation of guided tissue regeneration hydrogel membranes with antibacterial and biocompatible properties

The mechanical properties and structural stability of hydrogels and their performance in antidegradation can be enhanced by cross-linking them with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC). However, residual EDC compromises the biocompatibility of cross-linked hydrogels and the formability of un-cross-linked hydrogels. In this study, a facile process for preparing hydrogel regenerative membranes exerting antibacterial effects and containing gelatin/hyaluronic acid (G/HA) through solution casting was proposed. The membranes were cross-linked with EDC (G/HA-Ec-0H) and impregnated with two concentrations of the antibacterial agent of hinokitiol (G/HA-Ec-2H and G/HA-Ec-4H). Amide bonds formed, and the rate of active amino acid fixation was higher than 90%, which was directly proportional to the degree of cross-linking. The G/HA-Ec-2H and G/HA-Ec-4H groups with hinokitiol showed good antibacterial properties. The rate of hydrogel degradation decreased, and the integrity of sample morphology was maintained at more than 80% for over 3 days in the immersion. Then, the hydrogel structures relaxed and disintegrated through a rapid degradation reaction within 24 h. The biocompatibility results showed that low concentrations of hinokitiol did not affect cell viability. Moreover, hydrogel membranes after 14 days of cell incubation showed good cell adhesion and proliferation. In summary, the membrane biostability of the cross-linked gelatin/hyaluronan hydrogels was enhanced by EDC at a biocompatible concentration, and the functionalized group of G/HA-Ec-2H shows potential as a biodegradable material for biocompatible tissue-guarded regeneration membranes with antibacterial properties.

Codon Usage Selection Can Bias Estimation of the Fraction of Adaptive Amino Acid Fixations.

A growing number of molecular evolutionary studies are estimating the proportion of adaptive amino acid substitutions (α) from comparisons of ratios of polymorphic and fixed DNA mutations. Here, we examine how violations of two of the model assumptions, neutral evolution of synonymous mutations and stationary base composition, affect α estimation. We simulated the evolution of coding sequences assuming weak selection on synonymous codon usage bias and neutral protein evolution, α = 0. We show that weak selection on synonymous mutations can give polymorphism/divergence ratios that yield α-hat (estimated α) considerably larger than its true value. Nonstationary evolution (changes in population size, selection, or mutation) can exacerbate such biases or, in some scenarios, give biases in the opposite direction, α-hat < α. These results demonstrate that two factors that appear to be prevalent among taxa, weak selection on synonymous mutations and non-steady-state nucleotide composition, should be considered when estimating α. Estimates of the proportion of adaptive amino acid fixations from large-scale analyses of Drosophila melanogaster polymorphism and divergence data are positively correlated with codon usage bias. Such patterns are consistent with α-hat inflation from weak selection on synonymous mutations and/or mutational changes within the examined gene trees.

Effect of reassortment on the nucleotide and amino acid changes of human A/H3N2 RNP subunits during 1998–2009

Background The ribonucleoprotein (RNP) complex of influenza virus consists of four subunits PB2, PB1, PA, and NP, which are essential for replication. While reassortment plays an important role in the evolution and virulence of influenza viruses, limited studies have investigated the effect of reassortment on the evolution of the internal RNP subunits. Objective To examine the effect of reassortment on the nucleotide and amino acid changes of human A/H3N2 RNP subunits during the period 1998–2009. Study design A total of 240 A/H3N2 RNP subunit sequences were obtained from 23 clinical isolates in Australia and 217 isolates from National Centre for Biotechnology Information (NCBI) database. Rates of nucleotide change, amino acid substitution profile and phylogenetic analysis of each subunit during the 12-year period were determined using MEGA5. Result A major reassortment event within the A/H3N2 RNP subunits occurred in 2003. The rates of nucleotide change for PB2, PB1 and PA differed significantly before and after 2003, and were low compared to surface protein haemagglutinin (HA). No change was observed for NP. The amino acid substitution profile of the RNP subunits during the 12-year period showed the presence of simultaneous amino acid fixations in a pattern similar to HA, with an average amino acid fixation rate of 1.57 years. Conclusion Reassortment can affect the evolution of the influenza RNP subunits. Monitoring the amino acid substitution profile and evolution of the RNP subunits is necessary for the surveillance of future reassortments and emergence of potential virulence markers in the population.

Impact of CCR5delta32 Host Genetic Background and Disease Progression on HIV-1 Intrahost Evolutionary Processes: Efficient Hypothesis Testing through Hierarchical Phylogenetic Models

The interplay between C-C chemokine receptor type 5 (CCR5) host genetic background, disease progression, and intrahost HIV-1 evolutionary dynamics remains unclear because differences in viral evolution between hosts limit the ability to draw conclusions across hosts stratified into clinically relevant populations. Similar inference problems are proliferating across many measurably evolving pathogens for which intrahost sequence samples are readily available. To this end, we propose novel hierarchical phylogenetic models (HPMs) that incorporate fixed effects to test for differences in dynamics across host populations in a formal statistical framework employing stochastic search variable selection and model averaging. To clarify the role of CCR5 host genetic background and disease progression on viral evolutionary patterns, we obtain gp120 envelope sequences from clonal HIV-1 variants isolated at multiple time points in the course of infection from populations of HIV-1-infected individuals who only harbored CCR5-using HIV-1 variants at all time points. Presence or absence of a CCR5 wt/Δ32 genotype and progressive or long-term nonprogressive course of infection stratify the clinical populations in a two-way design. As compared with the standard approach of analyzing sequences from each patient independently, the HPM provides more efficient estimation of evolutionary parameters such as nucleotide substitution rates and d(N)/d(S) rate ratios, as shown by significant shrinkage of the estimator variance. The fixed effects also correct for nonindependence of data between populations and results in even further shrinkage of individual patient estimates. Model selection suggests an association between nucleotide substitution rate and disease progression, but a role for CCR5 genotype remains elusive. Given the absence of clear d(N)/d(S) differences between patient groups, delayed onset of AIDS symptoms appears to be solely associated with lower viral replication rates rather than with differences in selection on amino acid fixation.

Genome-Wide Evidence for Efficient Positive and Purifying Selection in Capsella grandiflora, a Plant Species with a Large Effective Population Size

Recent studies comparing genome-wide polymorphism and divergence in Drosophila have found evidence for a surprisingly high proportion of adaptive amino acid fixations, but results for other taxa are mixed. In particular, few studies have found convincing evidence for adaptive amino acid substitution in plants. To assess the generality of this finding, we have sequenced 257 loci in the outcrossing crucifer Capsella grandiflora, which has a large effective population size and low population structure. Using a new method that jointly infers selective and demographic effects, we estimate that 40% of amino acid substitutions were fixed by positive selection in this species, and we also infer a low proportion of slightly deleterious amino acid mutations. We contrast these estimates with those for a similar data set from the closely related Arabidopsis thaliana and find significantly higher rates of adaptive evolution and fewer nearly neutral mutations in C. grandiflora. In agreement with results for other taxa, genes involved in reproduction show the strongest evidence for positive selection in C. grandiflora. Taken together, these results imply that both positive and purifying selection are more effective in C. grandiflora than in A. thaliana, consistent with the contrasting demographic history and effective population sizes of these species.

Functional evolution of the trace amine associated receptors in mammals and the loss of TAAR1 in dogs

BackgroundThe trace amine associated receptor family is a diverse array of GPCRs that arose before the first vertebrates walked on land. Trace amine associated receptor 1 (TAAR1) is a wide spectrum aminergic receptor that acts as a modulator in brain monoaminergic systems. Other trace amine associated receptors appear to relate to environmental perception and show a birth-and-death pattern in mammals similar to olfactory receptors.ResultsAcross mammals, avians, and amphibians, the TAAR1 gene is intact and appears to be under strong purifying selection based on rates of amino acid fixation compared to neutral mutations. We have found that in dogs it has become a pseudogene. Our analyses using a comparative genetics approach revealed that the pseudogenization event predated the emergence of the Canini tribe rather than being coincident with canine domestication. By assessing the effects of the TAAR1 agonist β-phenylethylamine on [3H]dopamine uptake in canine striatal synaptosomes and comparing the degree and pattern of uptake inhibition to that seen in other mammals, including TAAR1 knockout mice, wild type mice and rhesus monkey, we found that the TAAR1 pseudogenization event resulted in an uncompensated loss of function.ConclusionThe gene family has seen expansions among certain mammals, notably rodents, and reductions in others, including primates. By placing the trace amine associated receptors in an evolutionary context we can better understand their function and their potential associations with behavior and neurological disease.

The Molecular Basis of Host Adaptation in Cactophilic Drosophila: Molecular Evolution of a GlutathioneS-Transferase Gene (GstD1) inDrosophila mojavensis

Drosophila mojavensis is a cactophilic fly endemic to the northwestern deserts of North America. This species includes four genetically isolated cactus host races each individually specializing on the necrotic tissues of a different cactus species. The necrosis of each cactus species provides the resident D. mojavensis populations with a distinct chemical environment. A previous investigation of the role of transcriptional variation in the adaptation of D. mojavensis to its hosts produced a set of candidate loci that are differentially expressed in response to host shifts, and among them was glutathione S-transferase D1 (GstD1). In both D. melanogaster and Anopheles gambiae, GstD1 has been implicated in the resistance of these species to the insecticide dichloro-diphenyl-trichloroethane (DDT). The pattern of sequence variation of the GstD1 locus from all four D. mojavensis populations, D. arizonae (sister species), and D. navojoa (outgroup) has been examined. The data suggest that in two populations of D. mojavensis GstD1 has gone through a period of adaptive amino acid evolution. Further analyses indicate that of the seven amino acid fixations that occurred in the D. mojavensis lineage, two of them occur in the active site pocket, potentially having a significant effect on substrate specificity and in the adaptation to alternative cactus hosts.

Recurrent Positive Selection at Bgcn, a Key Determinant of Germ Line Differentiation, Does Not Appear to be Driven by Simple Coevolution with Its Partner Protein Bam

Surveys of nucleotide sequence polymorphism in Drosophila melanogaster and Drosophila simulans were performed at 2 interacting loci crucial for gametogenesis: bag-of-marbles (bam) and benign gonial cell neoplasm (bgcn). At the polymorphism level, both loci appear to be evolving under the expectations of the neutral theory. However, ratios of polymorphism and divergence for synonymous and nonsynonymous mutations depart significantly from neutral expectations for both loci consistent with a previous observation of positive selection at bam. The deviations suggest either an excess of synonymous polymorphisms or an excess of nonsynonymous fixations at both loci. Synonymous evolution appears to conform to neutrality at bam. At bgcn, there is evidence of positive selection affecting preferred synonymous mutations along the D. simulans lineage. However, there is also a significantly higher rate of nonsynonymous fixations at bgcn within D. simulans. Thus, the deviation from neutrality detected by the McDonald-Kreitman test at these 2 loci is likely due to the selective acceleration of nonsynonymous fixations. Differences in the pattern of amino acid fixations between these 2 interacting proteins suggest that the detected positive selection is not due to a simple model of coevolution.

Multiple Signatures of Positive Selection Downstream of Notch on the X Chromosome in Drosophila melanogaster

To identify genomic regions affected by the rapid fixation of beneficial mutations (selective sweeps), we performed a scan of microsatellite variability across the Notch locus region of Drosophila melanogaster. Nine microsatellites spanning 60 kb of the X chromosome were surveyed for variation in one African and three non-African populations of this species. The microsatellites identified an approximately 14-kb window for which we observed relatively low levels of variability and/or a skew in the frequency spectrum toward rare alleles, patterns predicted at regions linked to a selective sweep. DNA sequence polymorphism data were subsequently collected within this 14-kb region for three of the D. melanogaster populations. The sequence data strongly support the initial microsatellite findings; in the non-African populations there is evidence of a recent selective sweep downstream of the Notch locus near or within the open reading frames CG18508 and Fcp3C. In addition, we observe a significant McDonald-Kreitman test result suggesting too many amino acid fixations species wide, presumably due to positive selection, at the unannotated open reading frame CG18508. Thus, we observe within this small genomic region evidence for both recent (skew toward rare alleles in non-African populations) and recurring (amino acid evolution at CG18508) episodes of positive selection.

Activity variation in alcohol dehydrogenase paralogs is associated with adaptation to cactus host use in cactophilicDrosophila

Drosophila mojavensis and Drosophila arizonae are species of cactophilic flies that share a recent duplication of the alcohol dehydrogenase (Adh) locus. One paralog (Adh-2) is expressed in adult tissues and the other (Adh-1) in larvae and ovaries. Enzyme activity measurements of the ADH-2 amino acid polymorphism in D. mojavensis suggest that the Fast allozyme allele has a higher activity on 2-propanol than 1-propanol. The Fast allele was found at highest frequency in populations that utilize hosts with high proportions of 2-propanol, while the Slow allele is most frequent in populations that utilize hosts with high proportions of 1-propanol. This suggests that selection for ADH-2 allozyme alleles with higher activity on the most abundant alcohols is occurring in each D. mojavensis population. In the other paralog, ADH-1, significant differences between D. mojavensis and D. arizonae are associated with a previously shown pattern of adaptive protein evolution in D. mojavensis. Examination of protein sequences showed that a large number of amino acid fixations between the paralogs have occurred in catalytic residues. These changes are potentially responsible for the significant difference in substrate specificity between the paralogs. Both functional and sequence variation within and between paralogs suggests that Adh has played an important role in the adaptation of D. mojavensis and D. arizonae to their cactophilic life.

Amino acid composition of Brazilian surubim fish ( Pseudoplatystoma coruscans) fed diets with different levels and sources of fat

Surubim ( Pseudoplatystoma coruscans) is a river fish from the Brazilian São Francisco basin which presents a great potential for commercialization. The amino acid composition of carcasses of surubim fed isoproteic diets with variable levels and sources of fat were determined. The increase of soybean oil at levels of 4%, 8% and 12% in the rations promoted a corresponding increase in nitrogen fixation in the fish carcass, reflected by higher amino acid contents. However, the application of 12% added amounts of pig lard, corn oil, linseed oil or soybean oil, as different sources of fat, did not promote much variation in the fish amino acid fixation. The determination of the essential amino acid composition in the fish carcasses and the A/E ratios of individual amino acids provided a pattern of amino acid requirements of surubim fish.

Excess of amino acid substitutions relative to polymorphism between X-linked duplications in Drosophila melanogaster.

We have obtained sequence polymorphism data from 13 genes belonging to 5 gene families in Drosophila melanogaster where the K(a)/K(s) between copies is greater than 1. Twelve of these 13 loci are X-linked. In general, there is evidence of purifying selection in all families, as inferred both from levels of silent and replacement variation and insertion/deletion variation, suggesting that the loci are likely functional. Shared polymorphisms indicative of gene conversion between paralogs are rare among the X-linked families, in contrast to available data from autosomal duplicates. McDonald-Kreitman tests between duplicates reveal an excess of amino-acid fixations between copies in the X-linked families, suggesting that the divergence between these loci was driven by positive selection. In contrast, available data from autosomal duplicates show a deficit of fixations, consistent with gene conversion being a strong homogenizing force.

Simultaneous hydrogen bonding and metal coordination interactions in the two-point fixation of amino acids with a bifunctional metalloporphyrin receptor

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimultaneous hydrogen bonding and metal coordination interactions in the two-point fixation of amino acids with a bifunctional metalloporphyrin receptorYasuhiro Aoyama, Masumi Asakawa, Atsushi Yamagishi, Hiroo Toi, and Hisanobu OgoshiCite this: J. Am. Chem. Soc. 1990, 112, 8, 3145–3151Publication Date (Print):April 1, 1990Publication History Published online1 May 2002Published inissue 1 April 1990https://doi.org/10.1021/ja00164a041RIGHTS & PERMISSIONSArticle Views301Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (970 KB) Get e-Alerts Get e-Alerts

ChemInform Abstract: Molecular Recognition. Part 2. Molecular Recognition of Amino Acids: Two‐Point Fixation of Amino Acids with Bifunctional Metalloporphyrin Receptors.

AbstractThe first successful two‐point fixation of amino acids and amino esters in nonionic forms via simultaneous metal‐coordination and hydrogen‐bonding interactions with bifunctional metalloporphyrin receptors is reported.

Molecular recognition. 2. Molecular recognition of amino acids: two-point fixation of amino acids with bifunctional metalloporphyrin receptors

Molecular recognition. 2. Molecular recognition of amino acids: two-point fixation of amino acids with bifunctional metalloporphyrin receptors

Polymères thiocarboxyliques, 3. Réaction avec les dérivés amines: ammoniac, amines, diamines, amino‐acides, dipeptides, colorants

AbstractDithiocarboxylic groups as side groups on linear or crosslinked polymers were transformed quantitatively into the corresponding thioamides by ammonia and primary or secondary amines, whereas reaction with 1,2‐diaminoethane led to poly(Δ2‐imidazoline)s. Due to the high reactivity of carboxymethyl diethioesters [(2‐thioacylthio)acetic acid] the fixation of amino acids, dipeptides, and amino dyes on macromolecular chains was realized with high yields.

Ligand-exchange separations of amino acids : I. Distribution equilibria of some amino acids between ammoniacal copper(II) nitrate solutions and phosphonic, carboxylic and iminodiacetic ion exchangers in the copper(II) form

The ligand-exchange process for the distribution of glycine, alanine and leucine between a copper(II) phosphonate resin and ammoniacal solutions of copper nitrate has been studied. The formation in both resin and solution phases of mixed CuA(NH3)i+ complexes (i = 1–3) was demonstrated. A theoretical expression for the distribution coefficient, taking into account the various parameters upon which it depends, has been established and verified experimentally. Some experiments carried out with carboxylic and iminodiacetic resin in the Cu(II) form confirmed the validity of the theoretical model.The distribution of an amino acid by ligand exchange occurs as a complex phenomenon that brings many equilibria into play. However, by simplifying the theory with some approximations, it is possible to describe the distribution by means of two equilibria, one of ion exchange and the other of the formation in solution of mixed complexes. This simplified theory clearly displays how the ammonia and copper(II) concentrations affect the amino acid fixation. Some experimental graphs illustrate the variation of the distribution coefficients for different amino acids with each of these parameters.Finally, some observations on the selectivity that may be expected from this process are made. In particular, it is shown how the optimal conditions for the separation of two amino acids can be determined.

Tintinnida: Feeding Experiments and Lorica Development1

SYNOPSIS. These experiments describe culturing conditions and autoradiographic methods for investigating food utilization and amino acid fixation for 2 species of Tintinnida.