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The Bicoid-based anterior patterning system of Drosophila embryogenesis appears to be unique to higher dipterans. A new study suggests how this may have evolved out of an alternative mechanism based on cooperating Orthodenticle and Hunchback proteins, the two mechanisms intersecting at the level of downstream target genes.
Many components of the innate immune system in vertebrates can be reliably traced to urochordates and successful strategies for the detection and elimination of pathogens are present at that level of animal evolution, but the issue of where and how the adaptive immune system emerged is still obscure. There is a paucity of evidence for a gradual transition from the innate immune system of invertebrates to the recombinatorial immune system of higher vertebrates. None of the classical elements of MHC based transplantation immunity (MHC, TCR) or humoral immunity (Ig) have been found in urochordates or Agnathans. Nevertheless there is abundant evidence for adaptive immune responses in the agnathans. This remarkable paradox raises a number of questions. How do these ancestral chordates discriminate between the constituents of the external world and the constituents of "self"? Are these strategies universal within the animal kingdom and among chordates, or are different strategies used by representatives of the different taxonomic groups? The current state of our knowledge indicates that the immune system of lower chordates is very different from that of cartilaginous fishes. Pure homology hunting for vertebrate-specific immuno-relevant molecules in invertebrates is therefore of limited value. A more promising approach may involve unbiased functional screening methods. To understand better the evolution of adaptive immune systems, more comparative data from jawless vertebrates (lamprey or hagfish) and a representative of Acrania (e.g. Amphioxus) are clearly needed.
A large body of sequence data has accumulated for the chloroplast-encoded gene ribulose-1,5-biphosphate carboxylase/oxygenase (rbcL) as the result of a cooperative effort involving many laboratories. The data span all seed plants, including most major lineages from the angiosperms, and as such they provide an unprecedented opportunity to study plant evolutionary history. The full analysis of this large data set poses many problems and opportunities for plant evolutionary biologists and for biostatisticians.
Immunoglobulin variable domains are generally thought of as well conserved platforms providing the base for antigen binding loops of highly varying sequence and structure. However, domain evolution must ensure a balance between optimizing antigen affinity and the requirements of a stable, cooperatively folding domain. Since random mutations can carry a significant penalty for domain stability, constraints are imposed both on the repertoire of germline sequences and on somatic amino acid replacements during affinity maturation. Analyzing these constraints in the conceptual framework of statistical mechanics, we have been able to predict stabilizing mutations in the McPC603 V kappa domain from sequence information alone with better than 60% success rate. The validity of this concept not only has far reaching implications for antibody engineering but may also be generalized to engineer other proteins for higher stability.
Mammals and birds have evolved three primary, discrete, interrelated emotion-motivation systems in the brain for mating, reproduction, and parenting: lust, attraction, and male-female attachment. Each emotion-motivation system is associated with a specific constellation of neural correlates and a distinct behavioral repertoire. Lust evolved to initiate the mating process with any appropriate partner; attraction evolved to enable individuals to choose among and prefer specific mating partners, thereby conserving their mating time and energy; male-female attachment evolved to enable individuals to cooperate with a reproductive mate until species-specific parental duties have been completed. The evolution of these three emotion-motivation systems contribute to contemporary patterns of marriage, adultery, divorce, remarriage, stalking, homicide and other crimes of passion, and clinical depression due to romantic rejection. This article defines these three emotion-motivation systems. Then it discusses an ongoing project using functional magnetic resonance imaging of the brain to investigate the neural circuits associated with one of these emotion-motivation systems, romantic attraction.
1. Overexpression of the c-myc oncogene is associated with a variety of both human and experimental tumours, and cooperation of other oncogenes and growth factors with the myc family are critical in the evolution of the malignant phenotype. 2. Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human transforming growth factor (TGF-alpha) cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumourigenesis. 3. Coexpression of c-myc and TGF-alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumours were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. 4. These observations suggest that the interaction of c-myc and TGF-alpha, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. 5. We have now extended these studied and examined the interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in the transgenic mouse model. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Similarly, tumour promotion by phenobarbitone was completely inhibited in the c-myc/HGF double transgenic mice whereas phenobarbitone was an effective tumour promoter in the c-myc single transgenic mice. 6. The results indicate that HGF may function as a tumour suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. Furthermore, we show for the first time that interaction of c-myc with HGF or TGF-alpha results in profoundly different outcomes of the neoplastic process in the liver.
Expression of the yeast arginase gene (CAR1) responds to both induction and nitrogen catabolite repression. Regulation is mediated through sequences that both positively and negatively modulate CAR1 transcription. A short sequence, 5'-TAGCCGCCGAGGG-3', possessing characteristics of a repressor binding site, plays a central role in the induction process. A fragment containing this upstream repression sequence (URS1) repressed gene expression when placed either 5' or 3' to the upstream activation sequences of the heterologous gene CYC1. Action of the URS and its cognate repressor was overcome by CAR1 induction when the URS was situated cis to the CAR1 flanking sequences. This was not observed, however, when it was situated downstream of a heterologous CYC1 upstream activation sequence indicating that URS function is specifically neutralized by cis-acting elements associated with CAR1 induction. Searches of sequences in various gene banks revealed that URS1-like sequences occur ubiquitously in genetic regulatory regions including those of bacteriophage lambda, yeast, mammalian, and viral genes. In a significant number of cases the sequence is contained in a region associated with negative control of yeast gene regulation. These data suggest the URS identified in this work is a generic repressor target site that apparently has been conserved during the evolution of transcriptional regulatory systems.
Overexpression of the c-myc oncogene is associated with a variety of both human and experimental tumors, and cooperation of other oncogenes and growth factors with the myc family are critical in the evolution of the malignant phenotype. The interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in a transgenic mouse model has been analyzed. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Furthermore, tumor promotion by phenobarbital was completely inhibited in the c-myc/HGF double transgenic mice, whereas phenobarbital was an effective tumor promoter in the c-myc single transgenic mice. The results indicate that HGF may function as a tumor suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine.
Molecular dynamics simulations of the binding of the heterochiral tripeptide KkN to the transactivation responsive (TAR) RNA of HIV-1 is presented, using an all-atom force field with explicit water. To obtain starting structures for the TAR-KkN complex, semirigid docking calculations were performed that employ an NMR structure of free TAR RNA. The molecular dynamics simulations show that the starting structures in which KkN binds to the major groove of TAR (as it is the case for the Tat-TAR complex of HIV-1) are unstable. On the other hand, the minor-groove starting structures are found to lead to several binding modes, which are stabilized by a complex interplay of stacking, hydrogen bonding, and electrostatic interactions. Although the ligand does not occupy the binding position of Tat protein, it is shown to hinder the interhelical motion of free TAR RNA. The latter is presumably necessary to achieve the conformational change of TAR RNA to bind Tat protein. Considering the time evolution of the trajectories, the binding process is found to be ligand-induced and cooperative. That is, the conformational rearrangement only occurs in the presence of the ligand and the concerted motion of the ligand and a large part of the RNA binding site is necessary to achieve the final low-energy binding state.
The authors present a case of a 29 year old patient who has been diagnosed on the right eye with Cogen-Reese syndrome and secondary glaucoma in 1997. This case came in the Ophtalmologic department from the lassy Railway Hospital in August 2000. For the treatment of the glaucoma and other associated complications it was realised on this eye: Cairns trabeculectomy with 5 FU, perforated keratoplasty, Laserphaco with PC-IOL, Laser selerostomy, goniotrepanation, explant of the IOL. Despite of the best cooperation of the patient and the numerous applicated therapeutical methods this case has a harm evolution and the obtaining of a morpho-functional balance on this eye seems to be a purpose impossible to reach.
The paper deals with the milestones of the space biomedicine advancement, its integration in the system of sciences and the life of humanity, and the role of Oleg G. Gazenko in its evolution.
A new lysozyme (cv-lysozyme 2) with a MALDI molecular mass of 12 984.6 Da was purified from crystalline styles and digestive glands of eastern oysters (Crassostrea virginica) and its cDNA sequenced. Quantitative real time RT-PCR detected cv-lysozyme 2 gene expression primarily in digestive gland tissues, and in situ hybridization located cv-lysozyme 2 gene expression in basophil cells of digestive tubules. Cv-lysozyme 2 showed high amino acid sequence similarity to other bivalve mollusk lysozymes, including cv-lysozyme 1, a lysozyme recently purified from C. virginica plasma. Differences between cv-lysozyme 2 and cv-lysozyme 1 molecular characteristics, enzymatic properties, antibacterial activities, distribution in the oyster body and site of gene expression indicate that the main role of cv-lysozyme 2 is in digestion. While showing that a bivalve mollusk employs different lysozymes for different functions, findings in this study suggest adaptive evolution of i type lysozymes for nutrition.
The species of thrips found on Acacia constitute a major component of the Australian thrips fauna, with at least 235 species in more than 30 genera, many of these being in the process of description as new. These thrips exhibit social behaviours, ranging from solitary and colonial species to a variety of more complex social organisations. Furthermore, the domiciliary habits of these species include domicile construction, gall induction, and opportunistic use of abandoned galls and domiciles. This suite of thrips also includes a variety of inquiline and kleptoparasitic taxa. To understand how these various traits have evolved and interact in this diverse group, we have reconstructed a phylogeny for 42 species of thrips associated with Acacia around Australia. We obtained DNA sequence data from two nuclear genes (Elongation Factor-1alpha and wingless) and one mitochondrial gene (cytochrome oxidase I) and analysed these using maximum parsimony and maximum likelihood methods. A phylogeny resulting from such analysis allows inference of evolutionary transitions in domiciliary habits, social organisations, and parasitic behaviours. Gall induction and parasitic behaviour are postulated to each have a single origin, with no losses of either trait. Once parasitism evolved a remarkable radiation followed that allowed exploitation of very diverse hosts. Our data do not allow hypotheses of single versus multiple origins of domicile building to be resolved while opportunistic gall use appears to have arisen several times.
Scientific development is pregnant with a breakthrough, epigenetic studies are pushing the genetics forward. Epigenetics is the study of heritable changes in gene expression that occurs without a change in DNA sequence. Epigenetics not only has practical significance for medicine and agriculture, but also provides new views on understanding heredity and evolution. Human genome contains information in two forms: the genetic information provides the blueprint for the manufacture of all the proteins necessary to create a living thing while the epigenetic information provides instructions on how, where, and when the genetic information should be used. The interrelationship of genetics and epigenetics is like a yin-yan, they are different from each other, and cooperatively take part in regulation of a variety of living activities. In this paper concept of gene and problems of evolution has been also discussed according to epigenetic viewpoints.
A biophysical theory is presented that supports a causal link between EMF exposures and the different biological endpoints of cancer and spontaneous abortion. The model for time-dependent instability of DNA specificity [Biochem. Genet. 32, 383 (1994)] is assumed to have been operational since DNA became selected as the molecular structure for the genome. Species were consequently required to adapt mechanisms to protect haploid gene pools from the continuous time-dependent accumulation of evolutionary base substitutions. To this end, conserved genetic domains containing mutation-intolerance thresholds are a result of natural selection operating on time-dependent base substitutions. "P53-type" genes are examples of such conserved domains with point mutation thresholds. When the oocyte is fertilized, conserved domains express wild type keto-amino genetic information. During subsequent development and growth, time-dependent evolution events populate G-C sites with enol-imine stationary states that can be transcribed and/or replicated to express transversion and transition mutations. As the level of evolution events would approach the intolerance threshold in the haploid genome, point mutation sensitive genes from conserved diploid domains, e.g. "p53-type" genes, would generate amino acid substituted proteins that have been evolutionarily selected to participate in species preservation by removing from the gene pool those haploid genomes containing advanced levels of mutation which, if propagated, would be inconsistent with survival. Consistent with the evolutionary origin of cancer hypothesis [Cancer Biochem. Biophys: 13, 147 (1993)], perturbations that would enhance rates of populating G-C sites with enol-imine states could accelerate point mutation "activation" of "p53-type" genes that could be manifested as premature cancer in living populations or expressed as spontaneous abortion in unborn populations. The evolution event "rate constant" is (gamma/h)2 where gamma is the quantum mechanical energy shift between G-C states. This expression implies that "additional" magnetic fields could increase rates of populating enol-imine states due to Lorentz force momentum transfer to metastable proton oscillators where induced electric fields and local currents would subject elevated energy proton oscillators to collisional de-exciatations which would increase the energy density of chemical bonds that support hydrogen bonds in DNA, thereby introducing larger energy shift values in (gamma/h)2. This hypothesis is explored for "additional" magnetic fields in the range of 0.15 to 0.01 gauss where the influence of magnetic enhancement energies on rates of populating enol-imine stationary states is evaluated, using Gurney and Condon tunneling time calculations for unperturbed and magnetically enhanced protons to escape metastable keto-amino energy wells. Model calculations are qualitative and are consistent with the experimentally testable hypothesis that "additional" magnetic fields could cause increased rates of accumulating evolutionary base substitutions, thereby increasing probabilities of activating "p53-type" genes which could cause increased incidence of spontaneous abortion in unborn populations and increased incidence of cancer in living populations.
Gene duplication is commonly regarded as the main evolutionary path toward the gain of a new function. However, even with gene duplication, there is a loss-versus-gain dilemma: most newly born duplicates degrade to pseudogenes, since degenerative mutations are much more frequent than advantageous ones. Thus, something additional seems to be needed to shift the loss versus gain equilibrium toward functional divergence. We suggest that epigenetic silencing of duplicates might play this role in evolution. This study began when we noticed in a previous publication (Lynch M, Conery JS [2000] Science 291:1151-1155) that the frequency of functional young gene duplicates is higher in organisms that have cytosine methylation (H. sapiens, M. musculus, and A. thaliana) than in organisms that do not have methylated genomes (S. cerevisiae, D. melanogaster, and C. elegans). We find that genome data analysis confirms the likelihood of much more efficient functional divergence of gene duplicates in mammals and plants than in yeast, nematode, and fly. We have also extended the classic model of gene duplication, in which newly duplicated genes have exactly the same expression pattern, to the case when they are epigenetically silenced in a tissue- and/or developmental stage-complementary manner. This exposes each of the duplicates to negative selection, thus protecting from "pseudogenization." Our analysis indicates that this kind of silencing (i) enhances evolution of duplicated genes to new functions, particularly in small populations, (ii) is quite consistent with the subfunctionalization model when degenerative but complementary mutations affect different subfunctions of the gene, and (iii) furthermore, may actually cooperate with the DDC (duplication-degeneration-complementation) process.
Win-stay, lose-shift, the principle to retain a successful action is a simple and general learning rule that can be applied to all types of repeated decision problems. In this paper I consider win-stay, lose-shift strategies with diverse memory sizes and strategies that adapt their aspiration levels, i.e. the payoff level considered as "success". I study their evolution for the Prisoner's Dilemma, as well as in a rapidly changing environment, where a randomly selected game is assigned to the players. For win-stay, lose-shift strategies with memory one the average payoffs are computed and their evolutionary stability is discussed. Using computer simulations I show that the win-stay, lose-shift strategies with longer memory are very successful both for the Prisoner's Dilemma, where cooperation dominates even for high noise levels, and the randomly assigned games, where the players achieve nearly the expected Pareto optimal payoffs. I discuss the impact of noise and show that the memory length of the players increases with the noise level. These results indicate that the win-stay, lose-shift principle is a very successful strategy in repeated games with noise.
Economists and psychologists have been testing Nash equilibrium predictions of game theory models of human behavior. In many instances, humans do not conform to the predictions. These results are of great interest to biologists because they also raise questions about well-known ESS models of cooperation. Cooperation in certain one-shot, anonymous interactions, and a willingness to punish others at a net cost to oneself are some of the most intriguing deviations from standard theory. One proposed explanation for these results that is receiving increasing attention invokes the cultural group selection of 'other regarding' social norms. We critically review this explanation. We conclude that experimental results reveal limits in two implicit models of cognitive structure commonly employed by economists and evolutionary biologists.