Phototautomerism of the GC base pair of DNA

Electronic spectra and ground and excited state electronic structures of normal G and rare tautomeric G1z.sbnd;C1 base pairs as well as of the individual rare tautomeric bases (purines and pyrimidines) have been studied using the VE-PPP molecular orbital method. The nature and consequences of the lowest energy purine-localized and purine to pyrimidine charge transfer type π?π1 singlet excitations of the base pairs have been investigated. The results indicate that in these excited states, particularly in the charge transfer excited state, the probability for the GC base pair to change over to G1C1 would be larger than in the ground state. The likeliness of the relevance of results obtained experimentally by other workers from the study of a model system to the GC base pair is discussed.     

Expression of pair rule gene orthologs in the blastoderm of a myriapod: evidence for pair rule-like mechanisms?

ABSTRACT: BACKGROUND: A hallmark of Drosophila segmentation is the stepwise subdivision of the body into smaller and smaller units, and finally into the segments. This is achieved by the function of the well-understood segmentation gene cascade. The first molecular sign of a segmented body appears with the action of the pair rule genes, which are expressed as transversal stripes in alternating segments. Drosophila development, however, is derived, and in most other arthropods only the anterior body is patterned (almost) simultaneously from a pre-existing field of cells; posterior segments are added sequentially from a posterior segment addition zone. A long-standing question is to what extent segmentation mechanisms known from Drosophila may be conserved in short-germ arthropods. Despite the derived developmental modes, it appears more likely that conserved mechanisms can be found in anterior patterning. RESULTS: Expression analysis of pair rule gene orthologs in the blastoderm of the pill millipede Glomeris marginata (Myriapoda: Diplopoda) suggests that these genes are generally involved in segmenting the anterior embryo. We find that the Glomeris pairberry-1 (pby-1) gene is expressed in a pair rule pattern that is also found in insects and a chelicerate, the mite Tetraynchus urticae. Other Glomeris pair rule gene orthologs are expressed in double segment wide domains in the blastoderm, which at subsequent stages split into two stripes in adjacent segments. CONCLUSIONS: The expression patterns of the millipede pair rule gene orthologs resemble pair rule patterning in Drosophila and other insects, and thus represent evidence for the presence of an ancestral pair rule-like mechanism in myriapods. We discuss the possibilities that blastoderm patterning may be conserved in long-germ and short-germ arthropods, and that a posterior double segmental mechanism may be present in short-germ arthropods.     

Male–male relationships in chimpanzees and the evolution of human pair bonds

The evolution of monogamy has been a central question in biological anthropology. An important avenue of research has been comparisons across “socially monogamous” mammals, but such comparisons are inappropriate for understanding human behavior because humans are not “pair living” and are only sometimes “monogamous.” It is the “pair bond” between reproductive partners that is characteristic of humans and has been considered unique to our lineage. I argue that pair bonds have been overlooked in one of our closest living relatives, chimpanzees. These pair bonds are not between mates but between male “friends” who exhibit enduring and emotional social bonds. The presence of such bonds in male–male chimpanzees raises the possibility that pair bonds emerged earlier in our evolutionary history. I suggest pair bonds first arose as “friendships” and only later, in the human lineage, were present between mates. The mechanisms for these bonds were co-opted for male-female bonds in humans.     

Synthesis and characterization of the anomeric pair of 17β-glucuronides of ethynylestradiol

The α- and β-anomers of the 17β-d-glucuronide conjugate of ethynylestradiol were synthesized by the SnCl₄-promoted reaction between β-acetoxy GAM and the t-17β-hydroxyl group of EE₂-3-acetate. The conjugates were resolved by crystallization and HPLC. Positive identification was established by u.v. spectrophotometry, i.r. and mass spectrometry and ¹H- and ¹³⁴C-n.m.r. The structure of the β-anomer was confirmed by X-ray crystallographic analysis. In addition, the α-anomer was refractory to hydrolysis by bovine β-glucuronidase, establishing a biochemical difference between the conjugate pair.     

Function of pair duets in the eastern whipbird: cooperative defense or sexual conflict?

Paired male and female eastern whipbirds, Psophodes olivaceus,sing precisely coordinated, male-led duets. Four broad explanationshave been proposed for the function of duets: 1) cooperativeresource defense, 2) prevention of partner usurpation, 3) defenseof an individual's own position within the partnership, or 4)mate identification and localization. These 4 hypotheses makedifferent predictions about how male and female residents shouldrespond to simulated intrusion by other pairs or individuals.We compared the behavioral and vocal responses of 20 pairs ofeastern whipbirds to simulated territorial intrusions by: 1)a solitary singing male, 2) a solitary singing female, and 3)a duetting pair. Males and females did not coordinate theirapproach to the playback speaker and showed sex-specific responsesto playback. Males did not respond differently to duetting versussolo singing intruders. By contrast, females approached moreclosely during solo female song than during solo male song orduet playback. Females also produced specific vocalizationsonly in response to duet and solo female playback. Both sexesapproached the speaker more closely and quickly during playbackof same-sex solo songs than opposite-sex solo songs. Finally,females answered more of their mate's songs during simulatedintrusion by a lone female than during simulated intrusion bya lone male. Our results suggest that duets in this speciesprimarily function to allow females to defend their exclusiveposition in a partnership. Mate defense by females is unusualin birds but may be promoted in eastern whipbirds by a female-biasedsex ratio and the need for exclusive access to male care. Thus,duets result from independent and conflicting strategies ofmate and territory defense in males and females.     

Assessing the preferred solution conformation of an interacting sense–antisense (complementary) peptide pair

Sense peptides and corresponding antisense peptides, are capable of making specific interactions. Such interactions may result from inter-peptide side-chain/side-chain contacts or because peptides adopt mutually complementary three-dimensional shapes. Using a combined ¹H NMR spectroscopy/molecular modeling approach to study the interactions between one sense peptide and its corresponding antisense peptide, data are produced that provide clear support for the former hypothesis.     

Changes in behaviour associated with pair formation in the polychaete Harmothoë imbricata (L.)

Spacing between individuals in populations of Harmothoë imbricata has been investigated both on the shore and in the laboratory. Males tend to occur closer together than females, and the mean male‐male individual distance measured was less than the mean distance between females; male—female distances for immature worms were intermediate. When worms mature they pair: the male mounts the female and lies across her dorsal surface. There is evidence that after spawning the members of a pair separate. Contact responses between worms have been investigated in the laboratory. Most encounters between immature worms lead to separation, as a result of one or both worms moving rapidly away from the other or fighting; females show more marked avoidance behaviour than males. The majority of male‐male and female‐female encounters between mature worms also lead to separation but in male‐female encounters the male usually mounts the female. A male which has mounted a female becomes highly aggressive and will attack intruding males but not females.     

Derivation and testing of pair potentials for protein folding. When is the quasichemical approximation correct?

Many existing derivations of knowledge-based statistical pair potentials invoke the quasichemical approximation to estimate the expected side-chain contact frequency if there were no amino acid pair-specific interactions. At first glance, the quasichemical approximation that treats the residues in a protein as being disconnected and expresses the side-chain contact probability as being proportional to the product of the mole fractions of the pair of residues would appear to be rather severe. To investigate the validity of this approximation, we introduce two new reference states in which no specific pair interactions between amino acids are allowed, but in which the connectivity of the protein chain is retained. The first estimates the expected number of side-chain contracts by treating the protein as a Gaussian random coil polymer. The second, more realistic reference state includes the effects of chain connectivity, secondary structure, and chain compactness by estimating the expected side-chain contrast probability by placing the sequence of interest in each member of a library of structures of comparable compactness to the native conformation. The side-chain contact maps are not allowed to readjust to the sequence of interest, i.e., the side chains cannot repack. This situation would hold rigorously if all amino acids were the same size. Both reference states effectively permit the factorization of the side-chain contact probability into sequence-dependent and structure-dependent terms. Then, because the sequence distribution of amino acids in proteins is random, the quasichemical approximation to each of these reference states is shown to be excellent. Thus, the range of validity of the quasichemical approximation is determined by the magnitude of the side-chain repacking term, which is, at present, unknown. Finally, the performance of these two sets of pair interaction potentials as well as side-chain contact fraction-based interaction scales is assessed by inverse folding tests both without and with allowing for gaps.     

Extra‐pair paternity as a strategy to reduce the costs of heterospecific reproduction? Insights from the crow hybrid zone

Within hybrid zones of socially monogamous species, the number of mating opportunities with a conspecific can be limited. As a consequence, individuals may mate with a heterospecific (social) partner despite possible fitness costs to their hybrid offspring. Extra‐pair copulations with a conspecific may thus arise as a possible post hoc strategy to reduce the costs of hybridization. We here assessed the rate of extra‐pair paternity in the hybrid zone between all‐black carrion crows (Corvus (corone) corone) and grey hooded crows (C. (c.) cornix) and tested whether extra‐pair paternity (EPP) was more likely in broods where parents differed in plumage colour. The proportion of broods with at least one extra‐pair offspring and the proportion of extra‐pair offspring were low overall (6.98% and 2.90%, respectively) with no evidence of hybrid broods having higher EPP rates than purebred nests.     

Thermodynamic and structural properties of the specific binding between Ag ion and C:C mismatched base pair in duplex DNA to form C–Ag–C metal-mediated base pair

Metal ion-nucleic acid interactions have attracted considerable interest for their involvement in structure formation and catalytic activity of nucleic acids. Although interactions between metal ion and mismatched base pair duplex are important to understand mechanism of gene mutations related to heavy metal ions, they have not been well-characterized. We recently found that the Ag⁺ ion stabilized a C:C mismatched base pair duplex DNA. A C–Ag–C metal-mediated base pair was supposed to be formed by the binding between the Ag⁺ ion and the C:C mismatched base pair to stabilize the duplex. Here, we examined specificity, thermodynamics and structure of possible C–Ag–C metal-mediated base pair. UV melting indicated that only the duplex with the C:C mismatched base pair, and not of the duplexes with the perfectly matched and other mismatched base pairs, was specifically stabilized on adding the Ag⁺ ion. Isothermal titration calorimetry demonstrated that the Ag⁺ ion specifically bound with the C:C base pair at 1:1 molar ratio with a binding constant of 10⁶ M⁻¹, which was significantly larger than those for nonspecific metal ion-DNA interactions. Electrospray ionization mass spectrometry also supported the specific 1:1 binding between the Ag⁺ ion and the C:C base pair. Circular dichroism spectroscopy and NMR revealed that the Ag⁺ ion may bind with the N3 positions of the C:C base pair without distorting the higher-order structure of the duplex. We conclude that the specific formation of C–Ag–C base pair with large binding affinity would provide a binding mode of metal ion-DNA interactions, similar to that of the previously reported T-Hg-T base pair. The C–Ag–C base pair may be useful not only for understanding of molecular mechanism of gene mutations related to heavy metal ions but also for wide variety of potential applications of metal-mediated base pairs in various fields, such as material, life and environmental sciences.     

Role of terminal dipole charges in aggregation of α-helix pair in the voltage gated K+ channel

The voltage sensor domain (VSD) of the potassium ion channel KvAP is comprised of four (S1–S4) α-helix proteins, which are encompassed by several charged residues. Apart from these charges, each peptide α-helix having two inherent equal and opposite terminal dipolar charges behave like a macrodipole. The activity of voltage gated ion channel is electrostatic, where all the charges (charged residues and dipolar terminal charges) interact with each other and with the transmembrane potential. There are evidences that the role of the charged residues dominate the stabilization of the conformation and the gating process of the ion channel, but the role of the terminal dipolar charges are never considered in such analysis. Here, using electrostatic theory, we have studied the role of the dipolar terminal charges in aggregation of the S3b–S4 helix pair of KvAP in the absence of any external field (V = 0). A system attains stability, when its potential energy reaches minimum values. We have shown that the presence of terminal dipole charges (1) change the total potential energy of the charges on S3b–S4, affecting the stabilization of the α-helix pair within the bilayer lipid membrane and (2) the C- and the N-termini of the α-helices favor a different dielectric medium for enhanced stability. Thus, the dipolar terminal charges play a significant role in the aggregation of the two neighboring α-helices.     

A flipped ion pair at the dynein–microtubule interface is critical for dynein motility and ATPase activation

Dynein is a motor protein that moves on microtubules (MTs) using the energy of adenosine triphosphate (ATP) hydrolysis. To understand its motility mechanism, it is crucial to know how the signal of MT binding is transmitted to the ATPase domain to enhance ATP hydrolysis. However, the molecular basis of signal transmission at the dynein–MT interface remains unclear. Scanning mutagenesis of tubulin identified two residues in α-tubulin, R403 and E416, that are critical for ATPase activation and directional movement of dynein. Electron cryomicroscopy and biochemical analyses revealed that these residues form salt bridges with the residues in the dynein MT-binding domain (MTBD) that work in concert to induce registry change in the stalk coiled coil and activate the ATPase. The R403-E3390 salt bridge functions as a switch for this mechanism because of its reversed charge relative to other residues at the interface. This study unveils the structural basis for coupling between MT binding and ATPase activation and implicates the MTBD in the control of directional movement.     

A haplotype-linked four base pair deletion upstream of the Aγ globin gene coincides with decreased gene expression

Summary During normal human development, a switch is classically observed in the relative expression of the two globin genes, the G/A ratio varying from 70/30 at birth to 40/60 by the end of the first year. An exception to this developmental pattern is linked to the presence of an XmnI restriction site at a position — 158 to the Cap site of the G gene. Another exception is observed in individuals homozygous for two easily detectable variations of the A gene: the presence of a threonine residue at codon 75 and a HindIII site within the second intron. A 4-bp deletion has been described around position — 225 in some thalassemic patients presenting with these variations. In this study, we find this deletion to be haplotypelinked in a series of 156 individuals of various ethnic origins and presenting with various normal and pathological phenotypes. In sickle cell patients heterozygous for this 4-bp deletion, the relative expression of the A genes on the two chromosomes can be measured by estimating the AT and AI chains, the former always being synthesized at a lower rate. These results suggest a functional role for the deleted sequence.     

Were the main mountain ranges in the Korean Peninsula a glacial refugium for plants? Insights from the congeneric pair Lilium cernuum – Lilium amabile

The main Korean mountain range (the so-called “Baekdudaegan”), which stretches from north to south across most of the country, has been thought to harbor glacial refugia for boreal plant species, where they likely found relatively stable habitats and maintained large population sizes. Under this scenario, high levels of genetic variation and low or moderate degree of differentiation among populations within these species were expected. To test this hypothesis, we examined levels of allozyme diversity (14 loci) in eight populations of the boreal herb Lilium cernuum, which in Korea occurs largely along the Baekdudaegan and, as a reference, in eight populations of its congener Lilium amabile, a temperate species that is distributed on lower hillsides in peripheral regions of the Baekdudaegan. L. cernuum harbored higher levels of genetic variation within populations than L. amabile (%P = 49.1 vs. 25.0, A = 1.71 vs. 1.34, and H_e = 0.159 vs. 0.048). Genetic differentiation among populations was low for both species (F_ST = 0.119 and 0.014 for L. cernuum and L. amabile, respectively). A series of historical and ecological factors may explain the contrasting levels of genetic diversity between L. cernuum and L. amabile: occurrence within the main ranges of the Baekdudaegan (enduring the glacial periods in macrorefugia) vs. low elevation peripheral areas (in microrefugia) and shade-tolerant vs. shade-intolerant. This study, as well as previous population genetics studies, strongly suggests that the Baekdudaegan merits high priority for conservation given its proposed role as glacial refugia for montane species.     

Interaction-induced electric (hyper)polarizability in the dihydrogen–neon pair: basis set and electron correlation effects

We investigated the interaction (hyper)polarizability of neon–dihydrogen pairs by performing high-level ab initio calculations with atom/molecule-specific, purpose-oriented Gaussian basis sets. We obtained interaction-induced electric properties at the SCF, MP2, and CCSD levels of theory. At the CCSD level, for the T-shaped configuration, around the respective potential minimum of 6.437 a₀, the interaction-induced mean first hyperpolarizability varies for 5?<? R/a₀?<?10 as

$$ \left[{\overline{\beta}}_{\mathrm{int}}(R)\hbox{-} {\overline{\beta}}_{\mathrm{int}}\left({R}_{\mathrm{e}}\right)\right]/{e}^3{a_0}^3{E_{\mathrm{h}}}^{-2}=-0.91\left(R\hbox{-} {R}_{\mathrm{e}}\right)+0.50{\left(R\hbox{-} {R}_{\mathrm{e}}\right)}^2\hbox{--} 0.13{\left(R\hbox{-} {R}_{\mathrm{e}}\right)}^3+0.01{\left(R\hbox{-} {R}_{\mathrm{e}}\right)}^4. $$

Again, at the CCSD level, but for the L-shaped configuration around the respective potential minimum of 6.572 a₀, this property varies for 5?<? R/a₀?<?10 as

$$ \left[{\overline{\beta}}_{\mathrm{int}}(R)\hbox{-} {\overline{\beta}}_{\mathrm{int}}\left({R}_{\mathrm{e}}\right)\right]/{e}^3{a_0}^3{E_{\mathrm{h}}}^{-2}=-1.33\left(R\hbox{-} {R}_{\mathrm{e}}\right)+0.75{\left(R\hbox{-} {R}_{\mathrm{e}}\right)}^2-0.20{\left(R\hbox{-} {R}_{\mathrm{e}}\right)}^3+0.02{\left(R\hbox{-} {R}_{\mathrm{e}}\right)}^4. $$

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Graphical Abstract Interaction-induced mean dipole polarizability (\( \overline{a} \)) for the T-shaped configuration of H₂–Ne calculated at the SCF, MP2, and CCSD levels of theory

     

Can simple codon pair usage predict protein-protein interaction?

Deciphering functional interactions between proteins is one of the great challenges in biology. Sequence-based homology-free encoding schemes have been increasingly applied to develop promising protein-protein interaction (PPI) predictors by means of statistical or machine learning methods. Here we analyze the relationship between codon pair usage and PPIs in yeast. We show that codon pair usage of interacting protein pairs differs significantly from randomly expected. This motivates the development of a novel approach for predicting PPIs, with codon pair frequency difference as input to a Support Vector Machine predictor, termed as CCPPI. 10-fold cross-validation tests based on yeast PPI datasets with balanced positive-to-negative ratios indicate that CCPPI performs better than other sequence-based encoding schemes. Moreover, it ranks the best when tested on an unbalanced large-scale dataset. Although CCPPI is subjected to high false positive rates like many PPI predictors, statistical analyses of the predicted true positives confirm that the success of CCPPI is partly ascribed to its capability to capture proteomic co-expression and functional similarities between interacting protein pairs. Our findings suggest that codon pairs of interacting protein pairs evolve in a coordinated manner and consequently they provide additional information beyond amino acids-based encoding schemes. CCPPI has been made freely available at: http://protein.cau.edu.cn/ccppi.     

Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the Elα subunit

Summary We report the molecular characterization of a case of a functional PDH-El (E1 subunit of pyruvate dehydrogenase) deficiency, a cause of severe congenital lactic acidosis. Residual PDH-El activity was reduced to 10% of normal values, although the subunit appeared to be quantitatively and qualitatively normal at the protein level as determined by Western blotting. The sequence of PDH-El mRNA and the corresponding genomic DNA revealed an in-frame 21-bp insertion between codons 305 and 306 of the normal Ela cDNA. The mutational insert commences with a novel GAT codon and is a nearly perfect tandem duplication of the wild type DNA sequence. A serine phosphorylation site regulating the activity of the PDH complex is altered by this insertion, which in all likelihood is responsible for the functional enzymatic deficiency leading to lactic acidosis.     

Does nest predation risk affect the frequency of extra‐pair paternity in a socially monogamous passerine?

While considerable variations in both the frequency of extra‐pair paternity (EPP) and the behavioral events that produce it are recognized among species, populations, individuals, and breeding attempts, the determinants of these variations are surprisingly difficult to establish. Nest predation may be one such determinant, since it is the most important source of reproductive failure, and past studies have suggested a variety of reproductive flexibilities under nest predation risk. However, despite its potentially significant effect on mating behaviors, nest predation risk has rarely been discussed in association with variations in intraspecific EPP patterns. Here, we examined the effect of naturally occurring nest predation, which varied between sites, years, and breeding attempts, on patterns of EPP in 92 broods (132 adults and 710 nestlings) of the Japanese great tit Parus major minor. We found that the frequency of extra‐pair offspring was positively correlated with the nest predation rate, along with a correlation to breeding attempts in a season, but not with other factors such as individual quality or breeding density. Under high nest‐predation risk, it may be adaptive for males to search for additional extra‐pair copulation to spread the risk of losing all offspring and to invest less in mate‐guarding, which also enables females to seek additional extra‐mating. The results of this study suggest that nest predation risk, among other factors, may significantly influence paternity allocation in birds.