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At least 19 recordsLinked to original sources
PubMed1978

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

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.

Amino Acid Sequence↗
PubMed1979

Two types of amino acid substitutions in protein evolution.

The frequency of amino acid substitutions, relative to the frequency expected by chance, decreases linearly with the increase in physico-chemical differences between amino acid pairs involved in a substitution. This correlation does not apply to abnormal human hemoglobins. Since abnormal hemoglobins mostly reflect the process of mutation rather than selection, the correlation manifest during protein evolution between substitution frequency and physico-chemical difference in amino acids can be attributed to natural selection. Outside of 'abnormal' proteins, the correlation also does not apply to certain regions of proteins characterized by rapid rates of substitution. In these cases again, except for the largest physico-chemical differences between amino acid pairs, the substitution frequencies seem to be independent of the physico-chemical parameters. The limination of the substituents involving the largest physico-chemical differences can once more be attributed to natural selection. For smaller physico-chemical differences, natural selection, if it is operating in the polypeptide regions, must be based on parameters other than those examined.

Amino Acid Sequence↗
PubMed1975

The influence of amino acid substitutions on the conformational energy of cytochrome c.

Conformational energies have been evaluated for each of the staggered side-chain conformations associated with the 261 amino acid substitutions known to occur among 60 eucaryotic species. At least 86% of these substitutions can be sterically accommodated (one at a time) within the structure of horse-heart cytochrome c resulting from conformational energy refinement. Simultaneous incorporation of all pertinent amino acid substitutions found in eight representative species into the refined horse-heart structure is also shown to be sterically possible, with few exceptions. In two cases (Pekin duck cytochrome with 10 substitutions and Samia cynthia cytochrome with 24 substitutions), all substitutions could be readily incorporated, and the total energies associated with their computed structures differed by less than 10 kcal/mol from that of horse-heart cytochrome c. In the cytochromes from rattlesnake (22 substitutions), tuna (18 substitutions), and Neurospora crassa (36 substitutions), tyrosine could not be substituted for phenylalanine at position 46, within the constraints of the calculations. However, when all of the remaining substitutions were incorporated into these three cytochromes, their computed conformational energies differed by less than 30 kcal/mol from that of horse-heart cytochrome c. Between two and four amino acid substitutions cause high energies in the cytochromes from human, baker's yeast, and cotton seed, but all of the remaining substitutions are consistent with a low energy conformation. These results suggest that the structures of homologous proteins may be even more similar than has previously been recognized. Substitutions of all possible amino acid types at the invariant positions (where all eucaryotic cytochromes c bear the same amino acid) have revealed some cases where different amino acids can be accommodated, thus demonstrating that the biological constraints on amino acid substitutions are often different from the purely steric constraints investigated in this work.

Amino Acid Sequence↗
PubMed1978

Volume and polarity changes accompanied by amino acid substitutions in protein evolution.

We evaluated the volume and polarity changes accompanied by amino acid substitutions along branches of the phylogenetic trees of cytochrome c, myoglobin and hemoglobin alpha and beta chains. In most cases the volume changes accompanied by the substitutions were found to be much larger than the volume of cavities existing in the interior of X-ray-analysed proteins. This implies that the interior of the proteins is very flexible and the necessary space for a larger amino acid residue substitution can be provided by adjusting nearby structures. Also, the volume and polarity changes are not particularly dependent on whether the substituted site is located in the exterior or interior of the proteins. This result supports the concept of the covarions by Fitch and Markowitz, when combined with the known fact that the exterior sites are more variable than the interior ones during protein evolution.

Amino Acids↗
PubMed1976

Photolysis of N-methyl and N-acetyl substituted amino acids.

Experiments on the production of free radicals in aqueous solutions of N-methyl and N-acetyl substituted amino acids by UV light are reported. The ESR spectra observed at 77 K show that the bond of the CH3- group of these substances is ruptured to a great deal compared with other bond ruptures producing paramagnetic centres. But in N-methyl substituted amino acids the methyl radical is less predominant than in N-acetyl substituted ones. At temperatures higher than 200 K the ESR spectra of all substances studied in our experiments are similar. It is supposed that a radical is formed with an unpaired spin near an oxygen atom.

Electron Spin Resonance Spectroscopy↗
PubMed1977

[Effect of amino acid substitutions in the polypeptide chain of DNA-polymerase on manifestation of the mutator effect].

Thin map of gene 43, controlling the synthesis of T4 DNA polymerase, is obtained by mapping experiments performed with 39 amber mutants, and is used for analysis of the sites of DNA polymerase gene from the point of view of displaying the mutator effect. The mutant sites studied possessed different reaction on amino acid substitutions in the polypeptide chain of the enzyme. Most of sites of the DNA polymerase gene, with the exception of two "supersensitive", responsed only on the apparent type of the amino acid substitutions: the mutator effect of amber mutations, which are located at these sites, was exhibited only in the case of insertion of the definite amino acid in the respective point of polypeptide chain. The proposed system of amber mutations for studying the mutator effect, allowed the authors to obtain the data on the effect of concrete alterations in the polypeptide chain of the enzyme on the development of its mutator properties.

Alleles↗
PubMed1977

Hemoglobin Arlington Park. A new hemoglobin variant with two amino acid substitutions in the beta chain.

Hemoglobin Arlington Park was detected accidentally as result of the use of a hemolysate which contained hemoglobin with normal electrophoretic mobility as a control for peptide mapping. Peptide maps of this hemolysate revealed 3 new peptides resulting from 2 amino acid substitutions to give to new variant with the composition (beta6 Glu replaced by Lys, 95 Lys replaced by Glu).

Amino Acids↗
PubMed1977

Hemoglobin S Travis: a sickling hemoglobin with two amino acid substitutions [beta6(A3)glutamic acid leads to valine and beta142 (h20) alanine leads to valine).

Hb S Travis is a previously undescribed sickling hemoglobin with two amino acid substitutions in the beta chain: beta6 Glu leads to Val and beta142 Ala leads to Val. The beta6 Glu leads to Val mutation imparts to Hb S Travis the characteristic properties of sickling hemoglobin, namely its association with erythrocyte sickling, the insolubility of the hemoglobin in the reduced form, and a minimum gelling concentration value identical to Hb S. Unlike Hb S, Hb S Travis exhibits an increased oxygen affinity and a decreased affinity for 2,3-bisphosphoglycerate and inositol hexakisphosphate. In addition, the variant hemoglobin's tendency to autoxidize and its mechanical precipitability suggest that there are conformational differences between Hb S and Hb S Travis.

Alanine↗
PubMed1979

Amino acid substitution: its use in detection and analysis of genetic variants.

Techniques of chemical analysis, amino acid sequencing and autoradiography are being used to study the frequency of incorporation of normally noncoded amino acids into hemoglobins and seminal fluid proteins. We are studying, by the sequencing of radiolabeled proteins followed by the recovery of [3H]isoleucine phenylthiohydantoin by high-performance liquid chromatography, the frequency at which normally noncoded isoleucine is incorporated into hemoglobin because of base-substitution mutations versus translational errors. Irradiation increases the isoleucine content of human hemoglobin and the frequency of substitution of isoleucine for specific amino acids in rabbit hemoglobin. Studies to date indicate that these techniques have been developed sufficiently for initial analysis of the potential of drugs and environmental pollutants to induce base-substitution mutations in mammalian somatic cells.

Amino Acid Sequence↗
PubMed2025

Amino Acid Substitutions in the Na+/K+-ATPase May Contribute to Salinity Tolerance in Insects.

Environmental salinity levels vary naturally across terrestrial ecosystems but can be heightened locally by coastal proximity and desertification as well as human activities such as road salt application and agriculture. Since salt is essential for many physiological processes in insects, rising environmental sodium concentrations may drive behavioral changes, where insects select environments and food sources with suitable sodium levels, or evolutionary changes in constitutive or plastic physiological mechanisms to process salt, potentially altering ecological dynamics and species interactions.Numerous hematophagous (blood feeding) insects such as the yellow-fever mosquito Aedes aeqypti are known to be able to breed in relatively saline environments. Among phytophagous (plant feeding) insects, grasshoppers can be important herbivores in arid and coastal salt-affected regions, whereas the monarch butterfly (Danaus plexippus) appears to perform relatively well on milkweed host plants growing in roadsides influenced by salt runoff. Several of these insects share a common trait: amino acid substitutions in the first extracellular loop of the Na+/K+-ATPase (NKA), a sodium pump crucial for maintaining ion balance. For the monarch these substitutions confer resistance to toxic cardenolides from milkweeds, but it is unclear whether NKA substitutions may influence salt tolerance.Here, we investigate whether the NKA substitutions found in these insects may contribute to salt tolerance using gene-edited Drosophila melanogaster mutant strains as models. We show that flies with substitution Q111L (found in Aedes mosquitoes) or a combination of Q111L and A119S (found in grasshoppers) exhibited greater salt tolerance, whereas flies carrying the combination of substitutions found in the monarch (Q111V, A119S, and N122H) did not.Our results suggest that the monarch may rely on alternate mechanisms for salt tolerance and that its NKA substitutions are important primarily for cardenolide resistance. However, substitution Q111L and the combination of Q111L and A119S may be relevant for salt tolerance in a variety of insects. Uncovering mechanisms of salt tolerance enhances our understanding of species distributions, ecological interactions, and evolutionary physiology in response to changing environmental salinity levels.

Journal Article↗
PubMed1975

Branched-chain amino acid substitutions in the biosynthesis of the antibiotic actinomycin.

Actinomycins normally contain N-methyl-l-valine and either d-valine, d-alloisoleucine or both amino acids in the molecule. During antibiotic formation in a medium supplemented with one of the four isoleucine stereoisomers, Streptomyces parvulus and S. chrysomallus form complex actinomycin mixtures (C(1), C(2), C(3), E(1), and E(2)-like compounds). Although chromatographic techniques suggested that single homogeneous components had been isolated, subsequent studies indicated that such chromatographic fractions probably consisted of multiple isomers of actinomycin. Amino acid analyses revealed the presence of N-methylvaline and/or N-methylalloisoleucine and, in addition, d-isoleucine, d-valine, and d-alloisoleucine were frequently found in a given fraction.

Amino Acids↗