Evolutionary mechanisms of rib loss in anurans: a comparative developmental approach

ABSTRACT The presence of free ribs is presumed to be a primitive morphological character observed only in a few families of Recent anurans, whereas the absence of ribs has been considered to be a derived condition that is widespread within this order. A comparative study of rib development based on representatives of several anuran lineages (Alytes, Bombina, Bufo, Discoglossus, Hyla, Pelobates, Pelodytes, Rana, and Xenopus) reveals a previously undetected diversity of developmental features in the formation and interaction between neural arches and ribs. The absence of free ribs at premetamorphic or later stages is verified in some groups, but we present for the first time evidence of the existence of larval rib rudiments in others, both in the anterior (Rana, Hyla) and posterior (Bufo, Discoglossus, Pelobates) presacral regions. Heterochrony seems to have played a major role in the processes underlying rib reduction. The intracolumnar differences between anterior (V(2)-V(4)) and posterior (V(5)-V(8)) regions are based on perturbations in the timing of early differentiation. Furthermore, a clear shift in the relative timing of ossification among evolutionary lineages was detected. In this respect Xenopus has a highly derived condition. The use of the morphological character of "rib loss" in phylogenetic analyses must be reconsidered due to the different convergent developmental paths described here. The phylogenetic analysis of a "sequence units" matrix of rib development is compared with current anuran phylogenies. Some evolutionary information appears to be clearly present in the ontogenetic data of this "missing morphology," but its value for evolutionary inferences is rather limited.     

Evolutionary mechanisms: Modularity,morphogenetic fields of gene expression,genetic regulation

Modern concepts heterochrony mechanisms, taking into account the data on modularity of ontogenetic and evolutionary processes, morphogenetic fields of gene expression are considered. In the context of evolutionary changes, features of genetic regulation of heterochronies, and also suppression of gene activity by epigenetic regulation are analyzed. Features of the origin of evolutionary novelties due to heterochronies, macromutations, and divergence of duplicated genes, which result in the formation of new genes and gene families, are discussed.     

Evolutionary mechanisms in tropical ferns

Cytotaxonomic work on tropical fern floras has now reached the stage at which it is possible to compare different geographical regions meaningfully. It is also possible, although the evidence is on a more restricted scale, to compare the taxonomic and geographical incidence of different evolutionary mechanisms of the kind which can be investigated by the experimental techniques of biosystematics. Autopolyploidy, allopolyploidy, genetical speciation without visible chromosome changes, and speciation involving visible structural chromosome changes, are all now known to have taken place in tropical examples some of which will be illustrated. Certain types of change are restricted to certain fern genera being apparently absent from others. Such restrictions do not explain the marked regional peculiarities exhibited by Africa versus India, or by Malaya when compared with Ceylon or Jamaica. Interpretation of the results requires attention to be directed to factors in the past history of the various areas which might not otherwise be recognized.     

Evolutionary mechanisms of senescence

This paper reviews theories of the evolution of senescence. The population genetic basis for the decline with age in sensitivity of fitness to changes in survival and fecundity is discussed. It is shown that this creates a presure of selection that disproportionately favors performance early in life. The extent of this bias is greater when there is a high level of extrinsic mortality; this accounts for much the diversity in life-history patterns among different taxa. The implications of quantitative genetic theory for experimental tests of alternative population genetic models of senescence are discussed. In particular, the negative genetic correlations between traits predicted by the antagonistic pleiotropy model may be obscured by positive correlations that are inevitable in a multivariate system, or by the effects of variation due to deleterious mutations. The status of the genetic evidence relevant to these theories is discussed.     

Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behaviour

Williams syndrome, a rare disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, has long intrigued neuroscientists with its unique combination of striking behavioural abnormalities, such as hypersociability, and characteristic neurocognitive profile. Williams syndrome, therefore, raises fundamental questions about the neural mechanisms of social behaviour, the modularity of mind and brain development, and provides a privileged setting to understand genetic influences on complex brain functions in a 'bottom-up' way. We review recent advances in uncovering the functional and structural neural substrates of Williams syndrome that provide an emerging understanding of how these are related to dissociable genetic contributions characterized both in special participant populations and animal models.     

Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging

An unrealized potential to understand the genetic basis of aging in humans, is to consider the immense survival advantage of the rare individuals who live 100 years or more. The Longevity Gene Study was initiated in 1998 at the Albert Einstein College of Medicine to investigate longevity genes in a selected population: the “oldest old” Ashkenazi Jews, 95 years of age and older, and their children. The study proved the principle that some of these subjects are endowed with longevity-promoting genotypes. Here we reason that some of the favorable genotypes act as mechanisms that buffer the deleterious effect of age-related disease genes. As a result, the frequency of deleterious genotypes may increase among individuals with extreme lifespan because their protective genotype allows disease-related genes to accumulate. Thus, studies of genotypic frequencies among different age groups can elucidate the genetic determinants and pathways responsible for longevity. Borrowing from evolutionary theory, we present arguments regarding the differential survival via buffering mechanisms and their target age-related disease genes in searching for aging and longevity genes. Using more than 1,200 subjects between the sixth and eleventh decades of life (at least 140 subjects in each group), we corroborate our hypotheses experimentally. We study 66 common allelic site polymorphism in 36 candidate genes on the basis of their phenotype. Among them we have identified a candidate-buffering mechanism and its candidate age-related disease gene target. Previously, the beneficial effect of an advantageous cholesteryl ester transfer protein (CETP-VV) genotype on lipoprotein particle size in association with decreased metabolic and cardiovascular diseases, as well as with better cognitive function, have been demonstrated. We report an additional advantageous effect of the CETP-VV (favorable) genotype in neutralizing the deleterious effects of the lipoprotein(a) (LPA) gene. Finally, using literature-based interaction discovery methods, we use the set of longevity genes, buffering genes, and their age-related target disease genes to construct the underlying subnetwork of interacting genes that is expected to be responsible for longevity. Genome wide, high-throughput hypothesis-free analyses are currently being utilized to elucidate unknown genetic pathways in many model organisms, linking observed phenotypes to their underlying genetic mechanisms. The longevity phenotype and its genetic mechanisms, such as our buffering hypothesis, are similar; thus, the experimental corroboration of our hypothesis provides a proof of concept for the utility of high-throughput methods for elucidating such mechanisms. It also provides a framework for developing strategies to prevent some age-related diseases by intervention at the appropriate level.     

RAPD markers for constructing intraspecific tomato genetic maps

The existing molecular genetic maps of the tomato, Lycopersicon spp, are constructed based on isozyme and RFLP polymorphisms between tomato species. These maps are useful for certain applications but have few markers that exhibit sufficient polymorphisms for intraspecific analysis and manipulations within the cultivated tomato. The purpose of this study was to investigate the relative potential of RAPD technology, as compared to isozymes and RFLPs, to generate polymorphic DNA markers within cultivated tomatoes. Sixteen isozymes and 25 RFLP clones that were known to detect polymorphism between L. esculentum and L. pennellii, and 313 random oligonucleotide primers were examined. None of the isozymes and only four of the RFLP clones (i.e., 16%) revealed polymorphism between the cultivated varieties whereas up to 63% of the RAPD primers detected one or more polymorphic DNA fragments between these varieties. All RAPD primers detected polymorphism between L. esculentum and L. pennellii genotypes. These results clearly indicate that RAPD technology can generate sufficient genetic markers exploiting sequence differences within cultivated tomatoes to facilitate construction of intraspecific genetic maps.Abbreviations RFLP restriction fragments length polymorphism - RAPD random amplified polymorphic DNA - PCR polymerase chain reaction - QTLs quantitative trait loci     

Mourning response and intervention in stillbirth: An alternative genetic counseling approach

Abstract

Stillbirth is a frequently occurring tragedy that causes intense problems for parents experiencing it. A review of the literature suggests that the grief response of parents to stillbirth or neonatal death may present more problems than do other types of bereavement. An assessment of these problems suggests that a successful plan for management requires intervention as soon as possible after the death occurs. A protocol for such intervention is presented. It is suggested that such intervention is the proper domain of genetic counselors and represents an expanded approach to genetic counseling, particularly in the light of the recent movement toward a more psychologically oriented paradigm of genetic counseling.     

Evolutionary changes in the genetic code

The genetic code has been influenced by directional mutation pressure affecting the base composition of DNA, sometimes in the direction of increased GC content and at other times, in the direction of AT. Such pressure led to changes in species-specific usages of codons and tRNA anticodons, and also in amino acid assignments of codons in mitochondria and in several intact organisms. These code changes are probably recent evolutionary events. The genetic code is not 'frozen', but instead it is still evolving.     

An evolutionary approach to enzyme kinetics: Optimization of ordered mechanisms

A theoretical investigation is presented which allows the calculation of rate constants and phenomenological parameters in states of maximal reaction rates for unbranched enzymic reactions. The analysis is based on the assumption that an increase in reaction rates was an important characteristic of the evolution of the kinetic properties of enzymes. The corresponding nonlinear optimization problem is solved taking into account the constraint that the rate constants of the elementary processes do not exceed certain upper limits. One-substrate-one-product reactions with two, three and four steps are treated in detail. Generalizations concern ordered uni-uni-reactions involving an arbitrary number of elementary steps. It could be shown that depending on the substrate and product concentrations different types of solutions can be found which are classified according to the number of rate constants assuming in the optimal state submaximal values. A general rule is derived concerning the number of possible solutions of the given optimization problem. For high values of the equilibrium constant one solution always applies to a very large range of the concentrations of the reactants. This solution is characterized by maximal values of the rate constants of all forward reactions and by non-maximal values of the rate constants of all backward reactions. Optimal kinetic parameters of ordered enzymic mechanisms with two substrates and one product (bi-uni-mechanisms) are calculated for the first time. Depending on the substrate and product concentrations a complete set of solutions is found. In all cases studied the model predicts a matching of the concentrations of the reactants and the corresponding Michaelis constants, which is in good accordance with the experimental data. It is discussed how the model can be applied to the calculation of the optimal kinetic design of real enzymes.     

Evolutionary conservation of microtubule-capture mechanisms

The dynamic nature of microtubules allows them to search the three-dimensional space of the cell. But what are they looking for? During cellular morphogenesis, microtubules are captured at sites just under the plasma membrane, and this polarizes the microtubule array and associated organelles. Recent data indicate that the signalling pathways that are involved in regulating the different microtubule cortical interactions are not only conserved between species, but also that they function in diverse processes.     

An approach to early genetic alterations in precancerous cells

To investigate the potential role of the PTEN tumor-suppressor gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations of the PTEN gene, using a laser-assisted microdissection method. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42.1%), 6 of 22 clear cell carcinomas (27.3%) and 13 of 23 solitary endometrial cysts (56.5%). Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%) and 7 of 34 solitary endometrial cysts (20.6%). In 5 endometrioid carcinomas with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis. In 7 clear cell carcinomas with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis. In no cases there were LOH events in the endometriosis only. These results indicate that inactivation of the PTEN gene is an early event in the development of both endometrioid and clear cell carcinoma of the ovary. A laser-assisted microdissection method enables us to collect target cells without contamination by non-tumor cells. We expect that this technique will be very useful for investigating genetic alterations in cancerous or precancerous lesions. Early genetic alterations in various precancerous cells detected by light microscopy can be readily identified by the tissue-microdissection method.     

Computational centrosomics: An approach to understand the dynamic behaviour of centrosome

Centrosomes are the key regulating element of cell cycle progression. Aberrations in their functional mechanism leads to several cancer related disorders. Although genomic studies in the field of centrosome have been extensively carried out, with the lack of structural conformation, the proteomic analysis of pathological genetic mutation is still a challenging task. Several computational algorithms and high range force fields are used to design the 3D structure conformation of proteins, which has now become the leading platform for in-silico drug discovery approaches. Application of these highly efficient platforms in centrosomics studies will be a novel approach to develop an efficient drug therapy for the treatment of their dysfunction disorders.     

Evolutionary roots of genetic code

It is presented the modern state of the problem on abiogenic synthesis of molecular mechanisms connected with genetic information storage and transfer. On the base of experimental results it is suggested model of the common ancestor of tRNA and prime mechanism of the specific peptide synthesis.