Amino acid composition and the evolutionary rates of protein-coding genes

Summary Based on the rates of amino acid substitution for 60 mammalian genes of 50 codons or more, it is shown that the rate of amino acid substitution of a protein is correlated with its amino acid composition. In particular, the content of glycine residues is negatively correlated with the rate of amino acid substitution, and this content alone explains about 38% of the total variation in amino acid substitution rates among different protein families. The propensity of a polypeptide to evolve fast or slowly may be predicted from an index or indices of protein mutability directly derivable from the amino acid composition. The propensity of an amino acid to remain conserved during evolutionary times depends not so much on its being features prominently in active sites, but on its stability index, defined as the mean chemical distance [R. Grantham (1974) Science 185862–864] between the amino acid and its mutational derivatives produced by single-nucleotide substitutions. Functional constraints related to active and binding sites of proteins play only a minor role in determining the overall rate of amino acid substitution. The importance of amino acid composition in determining rates of substitution is illustrated with examples involving cytochrome c, cytochrome b₅,ras-related genes, the calmodulin protein family, and fibrinopeptides.     

Using Genome-Wide Protein Sequence Data to Predict Amino Acid Conservation

For most proteins, multiple sequence alignments are a viable method to identify functionally and structurally important amino acids, but for most organisms, there is a subset of proteins that are unique or found in a few closely related organisms. For these proteins, it is not possible to produce sequence alignments that are useful in identifying functionally or structurally important amino acids. We have investigated the relationship between amino acid conservation and five factors (the amino acid’s identity, N-terminal neighbor, C-terminal neighbor, the local hydropathy of surrounding amino acids, and the local expected net charge of the surrounding amino acids based on the primary sequence) in Escherichia coli proteins. For four of the factors examined (all but the amino acid’s identity), there is a significant relationship with conservation for some of the standard 20 amino acids. Using the combination of all five factors, we show that it is possible to calculate a score based on the primary sequences of a subset of E. coli proteins that has statistically significant predictive value with respect to predicting conserved amino acids in other E. coli proteins and Saccharomyces cerevisiae proteins. As these five variables show significant relationships with conservation, we have termed them conservation factors. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Subgrouping of bacterial populations by cellular fatty acid composition

Abstract The cellular fatty acid composition of six bacterial species isolated from the seeds and leaves of sugar beet ( Beta vulgaris ) and from soil were analysed. The quantitative data from the fatty acid methyl ester (FAME) profiles were highly reproducible. Numerical analysis of Xanthomonas maltophilia . FAME profiles sub-grouped strains according to when they were isolated in the growing season. The analytical method used was sensitive enough to differentiate strains of Klebsiella terrigena isolated from either soil or leaves. The results from this study confirm reports that analyses of bacterial FAME composition were rapid to perform, specific and allowed differentiation of strains within the same species.     

Evolutionarily Conserved Optimization of Amino Acid Biosynthesis

The “cognate bias hypothesis” states that early in evolutionary history the biosynthetic enzymes for amino acid x gradually lost residues of x, thereby reducing the threshold for deleterious effects of x scarcity. The resulting reduction in cognate amino acid composition of the enzymes comprising a particular amino acid biosynthetic pathway is predicted to confer a selective growth advantage on cells. Bioinformatic evidence from protein-sequence data of two bacterial species previously demonstrated reduced cognate bias in amino acid biosynthetic pathways. Here we show that cognate bias in amino acid biosynthesis is present in the other domains of life—Archaebacteria and Eukaryota. We also observe evolutionarily conserved underrepresentations (e.g., glycine in methionine biosynthesis) and overrepresentations (e.g., tryptophan in asparagine biosynthesis) of amino acids in noncognate biosynthetic pathways, which can be explained by secondary amino acid metabolism. Additionally, we experimentally validate the cognate bias hypothesis using the yeast Saccharomyces cerevisiae. Specifically, we show that the degree to which growth declines following amino acid deprivation is negatively correlated with the degree to which an amino acid is underrepresented in the enzymes that comprise its cognate biosynthetic pathway. Moreover, we demonstrate that cognate fold representation is more predictive of growth advantage than a host of other potential growth-limiting factors, including an amino acid’s metabolic cost or its intracellular concentration and compartmental distribution. Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users. Reviewing Editor: Dr. Niles Lehman Ethan O. Perlstein and Benjamin L. de Bivort contributed equally to this work.     

Correlations between nucleotide frequencies and amino acid composition in 115 bacterial species

We studied the correlations between amino acid composition and mononucleotide and dinucleotide frequencies in 115 bacterial genomes of varying G+C content. Observed amino acid frequencies were compared with those expected from the actual mononucleotide and dinucleotide frequencies. Both mononucleotide and dinucleotide frequencies correlate well with the amino acid frequency, with dinucleotide frequencies doing so better. Despite the strong correlations, some of the observed amino acid frequencies, in particular for Arg, Val, Asp, Glu, Ser, and Cys, were consistently different from predicted values in all genomes. We suggest that this variation from predicted values is a consequence of selection pressure at the level of amino acids, while the close correspondence to the predictions in residues such as Thr, Phe, Lys, and Asn arises only from mutation and selection pressure at the level of the nucleic acid sequences.     

Amino acid determination in some edible Mexican insects

Summary The amino acid contents of edible insects from different provinces of Mexico and reference proteins were analysed by reversed-phase high-performance liquid chromatography and ion exchange chromatography. The insect amino acid contents were higher than the adult requirements indicated by the WHO/FAO pattern.     

Amino acid derivatization and analysis in five minutes

A convenient method permits acid separation by capillary gas chromatography in minutes — the suitable analytic forms are prepared in seconds.     

Nonrandom amino acid substitution and estimation of the number of nucleotide substitutions in evolution

Summary A method of estimating the number of nucleotide substitutions from amino acid sequence data is developed by using Dayhoff's mutation probability matrix. This method takes into account the effect of nonrandom amino acid substitutions and gives an estimate which is similar to the value obtained by Fitch's counting method, but larger than the estimate obtained under the assumption of random substitutions (Jukes and Cantor's formula). Computer simulations based on Dayhoff's mutation probability matrix have suggested that Jukes and Holmquist's method of estimating the number of nucleotide substitutions gives an overestimate when amino acid substitution is not random and the variance of the estimate is generally very large. It is also shown that when the number of nucleotide substitutions is small, this method tends to give an overestimate even when amino acid substitution is purely at random.     

The broken-stick model for amino acid composition in proteins

Summary The relative abundances among the amino acids, which are functionally similar to one another, were explained by random partition of a unit interval.     

Amino acid profiles in some scented rice varieties

Summary Twelve scented (basmati) and one non-scented variety were analysed for their amino acid composition. The essential amino acid profiles of scented varieties when compared with non-scented, revealed that these varieties exhibited higher values, which ranged from 2.82 to 4.86 gm/100 gm protein for lysine, 1.92 to 3.13 for methionine, 1.67 to 4.23 for tyrosine, 3.65 to 4.91 for phenylalanine, 5.50 to 8.95 for leucine, 2.25 to 3.40 for isoleucine, 2.84 to 3.46 for threonine, 3.36 to 5.33 for valine. When these values were compared to FAO recommended standards, it was observed that most of the scented varieties had comparable or superior values, while varieties such as, Type 3, Basmati sufaid 100, Likitimachi, Randhunipagalu and Basmati 370 showed superior lysine, phenylalanine, leucine, and methionine content. These observations suggest that the scented varieties posses better amino acid profiles and exhibit superior nutritional qualities, which could be utilised in breeding varieties with improved amino acid composition.     

Compositional variation in bacterial genes and proteins with potential expression level

Usage of guanine and cytosine at three codon sites in eubacterial genes vary distinctly with potential expressivity, as predicted by Codon Adaptation Index (CAI). In bacteria with moderate/high GC-content, G(3) follows a biphasic relationship, while C(3) increases with CAI. In AT-rich bacteria, correlation of CAI is negative with G(3), but non-specific with C(3). Correlations of CAI with residues encoded by G-starting codons are positive, while with those by C-starting codons are usually negative/random. Average Size/Complexity Score and aromaticity of gene-products decrease with CAI, confirming general validity of cost-minimization principle in free-living eubacteria. Alcoholicity of bacterial gene-products usually decreases with expressivity.     

Nucleotide Composition Bias Affects Amino Acid Content in Proteins Coded by Animal Mitochondria

We show that in animal mitochondria homologous genes that differ in guanine plus cytosine (G + C) content code for proteins differing in amino acid content in a manner that relates to the G + C content of the codons. DNA sequences were analyzed using square plots, a new method that combines graphical visualization and statistical analysis of compositional differences in both DNA and protein. Square plots divide codons into four groups based on first and second position A + T (adenine plus thymine) and G + C content and indicate differences in amino acid content when comparing sequences that differ in G + C content. When sequences are compared using these plots, the amino acid content is shown to correlate with the nucleotide bias of the genes. This amino acid effect is shown in all protein-coding genes in the mitochondrial genome, including cox I, cox II, and cyt b, mitochondrial genes which are commonly used for phylogenetic studies. Furthermore, nucleotide content differences are shown to affect the content of all amino acids with A + T- and G + C-rich codons. We speculate that phylogenetic analysis of genes so affected may tend erroneously to indicate relatedness (or lack thereof) based only on amino acid content. Received: 3 July 1996 / Accepted: 6 November 1996     

嗜热与嗜常温微生物的蛋白质氨基酸组成比较

嗜热微生物的嗜热特性与其蛋白质的高度热稳定性紧密相关。为了探索嗜热蛋白质的热稳定机制,比较嗜热和嗜常温微生物的蛋白质在氨基酸组成上的差别,收集110对分别来自嗜热和嗜常温微生物的同源蛋白质序列,比较两组蛋白质各种氨基酸含量以及疏水性氨基酸组成、疏水性指数和荷电氨基酸组成的差别,结果两者在多种氨基酸含量上存在微小但统计学上显著的差别,嗜热蛋白质比嗜常温蛋白质具有较高的平均疏水性和荷电氨基酸组成。对两组蛋白质的“脂肪族氨基酸指数”进行分析,证明嗜热蛋白质之所以具有较高的脂肪族氨基酸指数是由于其亮氨酸含量较高,与影响该指数的其它几种氨基酸无关;从而认为该指数的意义值得怀疑。通过对大量同源嗜热蛋白质和嗜常温蛋白质氨基酸组成的比较,能够揭示一些有关蛋白质热稳定性的普遍规律。     

半滑舌鳎受精卵、卵黄囊仔鱼和开口仔鱼氨基酸及脂肪酸的变化

采用气相色谱仪和氨基酸分析仪测定了半滑舌鳎(Cynoglossus semilaevis)受精卵、卵黄囊仔鱼和开口仔鱼的氨基酸与脂肪酸组成的变化。结果表明:总氨基酸组成在受精卵和卵黄囊仔鱼之间变化明显,但是在卵黄囊仔鱼和开口仔鱼之间只有细微的变化。开口仔鱼与其摄食的轮虫的总必需氨基酸组成相关。受精卵、卵黄囊仔鱼、开口仔鱼的游离氨基酸含量分别为139 mg/g、3.6 mg/g和2.5 mg/g,占总氨基酸含量的22.3%、3.6%和2.5%。饱和脂肪酸的总量从受精卵到卵黄囊仔鱼明显下降,但是发育到开口仔鱼含量无显著变化。单不饱和脂肪酸和多不饱和脂肪酸的总量在不同发育阶段无显著变化,而EPA和DHA的含量从卵黄囊仔鱼到开口仔鱼有明显下降。这表明在早期发育阶段半滑舌鳎主要利用饱和脂肪酸作为能量代谢的基质,对饱和脂肪酸的利用程度大于单不饱和脂肪酸和多不饱和脂肪酸。半滑舌鳎似乎需要长链的多不饱和脂肪酸如EPA、DHA和ARA。     

SuccSite: Incorporating Amino Acid Composition and Informative k-spaced Amino Acid Pairs to Identify Protein Succinylation Sites

Protein succinylation is a biochemical reaction in which a succinyl group (-CO-CH2-CH2-CO-) is attached to the lysine residue of a protein molecule. Lysine succinylation plays important regulatory roles in living cells. However, studies in this field are limited by the difficulty in experimentally identifying the substrate site specificity of lysine succinylation. To facilitate this process, several tools have been proposed for the computational identification of succinylated lysine sites. In this study, we developed an approach to investigate the substrate specificity of lysine succinylated sites based on amino acid composition. Using experimentally verified lysine succinylated sites collected from public resources, the significant differences in position-specific amino acid composition between succinylated and non-succinylated sites were represented using the Two Sample Logo program. These findings enabled the adoption of an effective machine learning method, support vector machine, to train a predictive model with not only the amino acid composition, but also the composition of k-spaced amino acid pairs. After the selection of the best model using a ten-fold cross-validation approach, the selected model significantly outperformed existing tools based on an independent dataset manually extracted from published research articles. Finally, the selected model was used to develop a web-based tool, SuccSite, to aid the study of protein succinylation. Two proteins were used as case studies on the website to demonstrate the effective prediction of succinylation sites. We will regularly update SuccSite by integrating more experimental datasets. SuccSite is freely accessible at http://csb.cse.yzu.edu.tw/SuccSite/.     

Amino acid metabolism in hepatocytes isolated from lactating rats

Parenchymal hepatocytes isolated from lactating rats had similar rates of amino acid incorporation into protein, but increased rates of urea formation compared to hepatocytes from non-lactating rats. The increased urea formation may be due to increased amino acid transport and degradation. The liver contributes to the increased utilization of amino acids during lactation.     

Amino acid fermentation and hydrogen transfer in mixed cultures

Abstract The degradation of the following amino acids was investigated in mixed cultures obtained from a waste water purification plant: aspartate, glutamate, serine, alanine, valine and leucine. Inhibition of sulfate-reducing bacteria in these mixed cultures by molybdate was found to inhibit amino acid degradation. The degradation of serine, alanine, valine and leucine was accelerated considerably by active sulfate reduction. The fermentation of aspartate and glutamate was not stimulated by the presence of sulfate-reducing bacteria. The existence of species which are able to ferment valine and leucine by coupling their oxidation to the reduction of exogenous acetate to butyrate was demonstrated.     

Amino acid network and its scoring application in protein-protein docking

Protein-protein complex, composed of hydrophobic and hydrophilic residues, can be divided into hydrophobic and hydrophilic amino acid network structures respectively. In this paper, we are interested in analyzing these two different types of networks and find that these networks are of small-world properties. Due to the characteristic complementarity of the complex interfaces, protein-protein docking can be viewed as a particular network rewiring. These networks of correct docked complex conformations have much more increase of the degree values and decay of the clustering coefficients than those of the incorrect ones. Therefore, two scoring terms based on the network parameters are proposed, in which the geometric complementarity, hydrophobic-hydrophobic and polar-polar interactions are taken into account. Compared with a two-term energy function, a simple scoring function HPNet which includes the two network-based scoring terms shows advantages in two aspects, not relying on energy considerations and better discrimination. Furthermore, combing the network-based scoring terms with some other energy terms, a new multi-term scoring function HPNet-combine can also make some improvements to the scoring function of RosettaDock.     

Selection for Highly Biased Amino Acid Frequency in the TolA Cell Envelope Protein of Proteobacteria

The bacterial cell envelope protein TolA functions to maintain the integrity of the cell membrane. This protein contains high levels of alanine and lysine that are used in the formation of alpha helices, which are required for normal protein function. The neutral model of molecular evolution predicts that amino acid composition and nucleotide composition are driven by the underlying GC content, as a result of mutation bias. However, this study shows that selection has acted to maintain high levels of alanine and lysine in the TolA protein of Proteobacteria, which in turn has biased nucleotide composition in the corresponding tolA gene.     

Amino acid composition and N-terminal sequence of the NADP-linked glutamate dehydrogenase from Trypanosoma cruzi

Abstract The NADP-linked glutamate dehydrogenase (NADP-GDH) from epimastigotes of Trypanosoma cruzi , Tul 2 stock, has been purified by an improved procedure. The enzyme has subunit molecular weight (47 kDa), amino acid composition and N-terminal sequence similar to those of the NADP-GDH from Escherichia coli , including the N-terminal extension of 15 amino acids present in the E. coli enzyme, but not in the NADP-GDH from Neurospora crassa .