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Concentration-affinity equivalence in gene regulation: convergence of genetic and environmental effects.

It is proposed that equivalent phenotypic effects can be obtained by either structural changes in macromolecules involved in gene regulation or changes in activity of the structurally unaltered macromolecules. This equivalence between changes in activity (concentration) and changes in structure can come into play within physiologically plausible limits and seems to represent an important interface between environment and genome--namely, between environmentally determined and genetically determined gene expression. The equivalence principle helps explain the appearance of phenocopies. It also points to a general pathway favorable to the occurrence, during evolution, of frequent episodes corresponding to Waddington's genetic assimilation and is likely to represent one component of the system responsible for the high frequency of recurrence of parallel evolution.

Biological Evolution

Asymmetric Boltzmann machines.

We study asymmetric stochastic networks from two points of view: combinatorial optimization and learning algorithms based on relative entropy minimization. We show that there are non trivial classes of asymmetric networks which admit a Lyapunov function L under deterministic parallel evolution and prove that the stochastic augmentation of such networks amounts to a stochastic search for global minima of L. The problem of minimizing L for a totally antisymmetric parallel network is shown to be associated to an NP-complete decision problem. The study of entropic learning for general asymmetric networks, performed in the non equilibrium, time dependent formalism, leads to a Hebbian rule based on time averages over the past history of the system. The general algorithm for asymmetric networks is tested on a feed-forward architecture.

Algorithms

Mitosis and early meiosis in Tetrahymena pyriformis and the evolution of mitosis in the phylum Ciliophora.

The micronuclear mitotic spindle of Tetrahymena pyriformis contains several distinctive elements. The 150 or so continuous microtubules (MTs) form a peripheral sheath just inside the inner nuclear membrane while the kinetochore bundles traverse the center of the nucleoplasm. A new set of microtubules, the separation spindle, appears during the 10-fold nuclear elongation which occurs during the late anaphase. Both the separation spindle and peripheral sheath MTs are present in the macronucleus during macronuclear division but there are no definite kinetochore MTs. In the cresent stage of meiotic prophase both peripheral sheath and kinetochore MTs are present in the micronucleus. By using our own, and other workers', data in conjunction with the phylogenetic scheme for the ciliates which has been designed by Corliss (1974, 1975), we have attempted to trace out the evolutionary history of the various elements of the ciliate mitotic spindle. For example, the micronuclear separation spindle can be followed, from its point of origin within the primitive gymnostomes, throughout the phylum. The separation spindle of the macronucleus, by contrast, is lost at the level of the heterotrichs. Similarly, the anaphase breakdown and reconstitution of the nuclear envelope, which occurs in the primitive Loxodes magnus, can be followed up some phyletic branches, such as the heterotrichs, but in the suctorians and some other groups this feature seems to have been lost. Tracing the evolution of the ciliate mitotic spindle is made very difficult both by the incompleteness of the data and by what appear to be a number of cases of secondary reduction and parallel evolution. In general, however, the evolution of mitosis correlates well with the phylogeny of the ciliates constructed by Corliss and we consider this an independent substantiation of the general correctness of his phylogeny.

Biological Evolution

Sera from volunteers immunized by planned blood transfusions as source of DR cytotoxic typing reagents.

Sera from volunteers immunized with planned blood transfusions were tested for anti DR cytotoxic antibodies with a panel of HLA typed cultured human lymphoid cells using a variety of serological techniques. The majority of sera contained DR cytotoxic antibodies. The specificity of DR antibodies in seven sera was determined by testing them with a panel of B peripheral lymphocytes typed with DR alloantisera submitted to the 7th International Histocompatibility Workshop. The temporal evolution of DR and HLA-A and B cytotoxic antibodies was determined in two subjects by testing serial bleedings with B lymphoid cells, coated with Fab2 fragments from anti beta 2 mu and anti DR xenoantisera. Results indicated a parallel evolution of DR and HLA-A and B cytotoxic antibodies.

Antibody Specificity

Modern evolution of a single-copy gene: the immunoglobulin C kappa locus in wild mice.

The immunoglobulin kappa light-chain constant region gene (C kappa) has been cloned and sequenced from five wild mouse species. Analysis of these data has permitted an assessment of single-copy gene evolution during a limited time period as defined by the genus Mus. Sequence conservation was found to be as high (or higher) in the 5' and enhancer regions as in the coding region. The pattern of substitutions throughout these genes suggests that parallel evolution has occurred frequently and that substitutions at replacement sites have not decreased significantly, owing to saturation during this period of approximately 10 Myr. Phylogenetic relationships have been determined among these wild species as well as among members of the genus Rattus.

Animals

[Malignant non-Hodgkin's lymphoma associated with a serum monoclonal immunoglobulin].

Among the 394 non-Hodgkin's lymphomas (NHL) observed at our hospital over a thirteen year period, we have found 17 associated monoclonal gammopathies (4.3%). Fourteen gammopathies could be correlated to the lymphoid tumor due to a study of immunological membrane markers and to the comparative evolution of the disease and the monoclonal gammopathy. Two different groups could be distinguished: Six patients out of the fourteen studied (43%) had a gammopathy similar to the surface immunoglobulins of the tumour lymphoid cells. Seven of the seventeen showed, after treatment, a parallel evolution between the tumor and the gammopathy. This originates directly from the tumoral secretion and deserves to be classified among the B lymphoid excretory tumors. Six were IgM and one was IgG. Eight of the fourteen patients studied (57%) did not show any immunological relation between the lymphoma and the monoclonal gammopathy. The evolutions (10 of the 17 patients) of the tumor and of the gammopathy were independent. Among the eleven gammopathies (1 double gammopathy), 5 were IgG, 4 were IgA and 2 were IgM. The incidence of these gammopathies related to the total group tf lymphomas is 2.5%. Given the age of these patients, the association seems fortuitous.

Adult

Genomic and phenotypic diversification of Pseudomonas aeruginosa during sustained exposure to a ciliate predator.

UNLABELLED: Predator-mediated selection is an important ecological force shaping bacterial evolution, but its effects on genomic adaptation and virulence in opportunistic pathogens are not fully understood. Here, we used experimental evolution to study how exposure to the ciliate predator Tetrahymena thermophila affects Pseudomonas aeruginosa. Replicate populations were evolved for 60 days with or without the predator, followed by whole-genome shotgun metagenomic sequencing and phenotypic analyses. Both treatments showed strong selection and evidence of parallel evolution at gene and nucleotide levels, indicating constrained adaptation. However, predator exposure altered evolutionary dynamics. Predator-evolved populations showed a wider distribution of mutation frequencies, with many mutations persisting at intermediate frequencies, consistent with increased clonal interference and ongoing competition among lineages. In contrast, populations evolved without predators showed more high-frequency mutations, consistent with selective sweeps, although some low-frequency variants remained. Despite substantial genomic change, phenotypic outcomes were variable. Virulence in an invertebrate host model did not consistently increase. Instead, evolved isolates showed context-dependent changes, including modest decreases or occasional increases. Competition assays also showed no consistent fitness advantage for predator-evolved isolates, suggesting trade-offs between predator resistance and growth in other environments. Overall, predator-mediated selection reshaped evolutionary dynamics by maintaining diversity and altering the balance of lineages rather than producing uniform increases in virulence. These results highlight how ecological complexity influences adaptive evolution and the context-dependent nature of pathogen traits. IMPORTANCE: Opportunistic pathogens such as Pseudomonas aeruginosa often evolve in environmental settings before infecting hosts, raising questions about how ecological interactions influence virulence. Predator-mediated selection has been suggested to increase virulence via coincidental evolution, but evidence is inconsistent. Here, we show that exposure to a eukaryotic predator does not consistently elevate virulence but does reshape evolutionary dynamics by altering how mutations spread in populations. Predator-exposed populations retained more intermediate-frequency mutations, consistent with increased clonal interference and ongoing competition among lineages, whereas non-predator populations were dominated by selective sweeps. These differences were also reflected in functional targets of adaptation, with predator exposure favoring mutations in genes involved in environmental sensing and interaction. Together, these findings suggest that ecological complexity shapes the dynamics of adaptation rather than driving a single evolutionary outcome, highlighting that virulence is an emergent property influenced by underlying evolutionary processes.

Pseudomonas aeruginosa

[Morphological evolution of the first lower premolar of some higher primates].

Recent discoveries in Africa, in Asia and in Europe of new fossils attributed to the Ramapithecinae and/or to the Australopithecinae seem to point out the monocuspid origin of Man's first lower premolar the bicuspidy of the Gigantopithecidae, the Oreopithecidae' and the Hominidae' first lower premolar, reached at different geological ages, give an example of parallel evolution.

Animals

Evolution of transcribed and spacer sequences in the ribosomal RNA genes of Drosophila.

Examination of the ribosomal RNA (rRNA) gene of six sibling species that make up the D. melanogaster subgroup reveals that the nontranscribed spacer is highly conserved during evolution. Indeed, the spacer is at least as conserved as the transcribed rRNA sequence in four of the six species and only slightly less conserved in the others. These data support the hypothesis previously suggested (Tartof and Dawid, 1976) that selection has a significant role in maintaining the parallel evolution of genetically separate but homologous redundant gene clusters.

Animals

A rapid, light-induced transient in electron paramagnetic resonance signal II activated upon inhibition of photosynthetic oxygen evolution.

A rapid, light-induced reversible component in Signal II is observed upon inhibition of oxygen evolution in broken spinach chloroplasts. The inhibitory treatments used include Tris washing, heat, treatment with chaotropic agents, and aging. This new Signal II component is in a 1 : 1 ratio with Signal I (P700). Its formation corresponds to a light-induced oxidation which occurs in less than 500 mus. The subsequent decay of the radical results from a reduction which occurs more rapidly as this free radical component is complete following a single 10-mus flash, and it occurs with a quantum efficiency similar to that observed for Signal I formation. Red light is more effective than far-red light in the generation of this species, and, in preilluminated chloroplasts, 3-(3,4-dichlorophenyl)-1,1-dimethylurea blocks its formation. Inhibition studies show that the decline in oxygen evolution parallels the activation of this Signal II component. These results are interpreted in terms of a model in which two pathways, one involving water, the other involving the rapid Signal II component, compete for oxidizing equivalents generated by Photosystem II. In broken chloroplasts this Signal II pathway is deactivated and water is the principal electron donor. However, upon inhibition of oxygen evolution, the Signal II pathway is activated.

Chloroplasts

Trends in the functional morphology and sensorimotor control of feeding behavior in salamanders: an example of the role of internal dynamics in evolution.

Organisms are self-producing and self-maintaining, or "autopoietic" systems. Therefore, the course of evolution and adaptation of an organism is strongly determined by its own internal properties, whatever role "external" selection may play. The internal properties may either act as constraints that preclude certain changes or they open new pathways: the organism canalizes its own evolution. As an example the evolution of feeding mechanisms in salamanders, especially in the lungless salamanders of the family Plethodontidae, is discussed. In this family a large variety of different feeding mechanisms is found. The authors reconstruct this evolutionary process as a series of "bifurcation points" of either constraints or opportunities forming a sequence of preconditions for the formation of a high-speed projectile tongue characteristic of tropical salamanders. Furthermore, it is shown how parallel evolution of seemingly unrelated domains within an organism such as respiratory physiology, life history biology and pattern of ontogeny has rather direct relevance to the feeding biology, thus demonstrating that organisms always evolve as wholes.

Animals

[Biventricular functional adaptation during a prolonged race. An analysis of global and regional ventricular function].

To determine the effects of a six-hour competitive race on left and right ventricular performance, 99mTc gated blood pool scans were performed to 6 long distance runners before the race (rest), each hour during the race and one hour after concluding the exercise (recovery). Heart rate increased during the race, peaking at 4th hour of competition (55 +/- 3 to 110 +/- 9 lpm; p = 0.001). Evolution of right ventricular ejection fraction showed a similar behavior with the evolution of left ventricular ejection fraction during the competition (r = 0.39; p = 0.006). Blood volume in the lungs increased at the end of the race (index 1.13 +/- 0.14) normalizing at recovery (index 1.03 +/- 0.03). Left and right ventricular peak filling rate had an inverse correlation with pulmonary blood volume (r = -0.31; p = 0.041 and r = -0.47; p = 0.001 respectively). Both left and right ventricular ejection fraction had an inverse correlation with pulmonary blood volume (r = -0.38; p = 0.006 and r = -0.34; p = 0.01 respectively). The anteroseptal regional ejection fraction showed an inverse correlation with end-systolic and end-diastolic volume (r = -0.32; p = 0.03 and r = -0.4; p less than 0.01 respectively). The posterolateral region showed a parallel evolution with the global ejection fraction for both left and right ventricles (r = 0.57; p less than 0.0001 and r = 0.38; p = 0.009 respectively). In conclusion, a transient biventricular functional adaptation during a prolonged race is related to pulmonary blood volume redistribution and to a higher preload for both ventricles and a greater afterload for the right ventricle. The posterolateral and inferoapical regions show a similar behavior as both left and right ventricular ejection fraction, response that does not occur with the anteroseptal regional ejection fraction.

Adaptation, Physiological

Intra- and interspecies analyses of the carcinoembryonic antigen (CEA) gene family reveal independent evolution in primates and rodents.

Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders.

Animals

Lack of correlation between cardiac mass and arteriolar structural changes in mild-to-moderate hypertension.

A morphological restructuring of cardiac and arteriolar tissue is common in hypertension. The parallel evolution of these two processes as a compensatory response to pressure overload is a frequently assumed but unsubstantiated hypothesis. To evaluate this possibility, we have concomitantly measured left ventricular mass (LVM; two-dimensional echo) and minimal forearm vascular resistance (FVR; derived from the ratio of intra-arterial blood pressure: forearm blood flow by venous plethysmography) at maximal postischemic (13 min ischemia + 1 min hand exercise) reactive hyperemia. The study was performed on 29 essential hypertensive patients (15 males, 14 females, aged 50 +/- 10 years) who had not been undergoing treatment for hypertension for at least 15 days at the time of study. Minimum FVR was taken as a hemodynamic index of the integrated arteriolar lumen at the forearm level. LVM index and minimum FVR ranged from normal to clearly altered values. In spite of a wide spread of values, no correlation existed between the individual values of the two variables. Systemic mean blood pressure correlated with minimum FVR and tended to correlate with LVMI. Thus, morphological restructing of cardiac and arteriolar tissue does not seem to evolve in parallel in human hypertension. Pressure overload may contribute to cardiovascular hypertrophy, but other unrelated mechanisms may also underlie the development of cardiac and arteriolar abnormalities of human hypertension.

Arterioles

Evolution of mesenchymal cells in fetal rat lung.

The evolution of connective tissue cells in the developing fetal rat lung is studied under the electron microscope from the 15th until the 21st day of gestation and is compared to the evolution of epithelial cells. Three successive types of stem cells ("mesocytoblasts") are present during the first stages of lung development studied (15 to 18 days of gestation). These stem cells appear to be able to differentiate into fibroblasts or into smooth muscle cells, according to their localization along the broncho-alveolar tubule. Myoblasts are situated near the bronchial epithelium, whereas fibroblasts occur under the alveolar epithelium. Epithelo-mesenchymal interactions are assumed to play a role in this differentiation process. Synthesis of both, collagen and elastic fibers and of cytoplasmic filaments by fibroblasts as well as by myoblasts reveal the multiple potentialities of the mesenchymal stem cell and suggest a common origin. The early fibroblast in characterized by long cytoplasmic processes which contain numerous cytofilaments, and by the presence of collagen fibers in the vicinity of the cell. Later on, (20 days of gestation) the mature fibroblast of the lung mesenchyme shows areas of RER, glycogen and lipidic vacuoles in its cytoplasm. Cytofilaments are numerous within very long cytoplasmic processes and elastic and collagen fibers are very frequent beside the cytoplasmic membrane. The earliest fibroblast differentiation occurs under the epithelium of primitive respiratory bronchioles, which indicate the limit between the bronchial and the alveolar territories. Later on, differentiating fibroblasts are found throughout the whole alveolar walls. Connective tissue cells other than mesenchymal stem cells, fibroblasts or myoblasts are observed during lung development. Vacuolar cells, similar to Hofbauer cells, transiently appear on the 16th day of gestation. On the 20th and the 21st day macrophage-like cells are present in the septal space of the alveolar wall. The absence of intermediate stages of differentiation and parallel evolution of blood cells suggest that those connective tissue cells are differentiated elsewhere and have then migrated from blood into lung mesenchyme. No cell death has been observed in the developing lung.

Animals

Progress and challenges in psychosocial and behavioral research in cancer in the twentieth century.

Research in the psychosocial and behavioral aspects of cancer has shown steady growth since the 1950s, and its course of development has paralleled the history of medical techniques in treating cancer. Table 1 outlines this parallel evolution from the 1850s to the 1960s. The roles of the American Cancer Society and the National Cancer Institute (NCI) in spearheading and nurturing research in this area are documented. Interest in psychooncologic questions can be traced back for centuries to the search for etiologic factors and psychologic variables that would explain individual vulnerability to cancer. The first psychologic studies of cancer patients were reported in 1951 and 1952 from the Massachusetts General Hospital and Memorial Sloan-Kettering Cancer Center, respectively. The 1970s saw new interest in psychosocial and behavioral research with many issues being addressed for the first time: better care of the terminally ill through more humanistic approaches including better means of pain control; ethical concerns related to patient rights and their status as subjects in experimental protocols; trying to measure quality of life for cancer patients on protocols; seeing the need for multidisciplinary collaborative groups to make up for the absence of formal training in this area; and the need to design valid, accurate measuring scales specific to the symptomology of patients with cancer. Table 4 outlines how the 1980s gave increasing recognition and support to the psychosocial dimensions of cancer. This period produced a series of key conferences that examined a broad research and education perspective and produced recommendations that remain a benchmark in regard to instrumentation, conceptual models, pitfalls of psychosocial research, training, and education, and the organization of research efforts. New precision has been added to the field in the past 6 years: studies measuring concurrent psychologic, endocrine, and immune function; use of statistical modeling to incorporate quality of life data as a correction factor in survival data (TWiST and QALY); and broadened definitions of medical outcome to include functional status, thus allowing advances in psychiatric measurements to help answer questions in cancer. The challenges for the 1990s are identified in a summary in Table 9. Especially noteworthy is the observation that the comprehensive research needed today cannot be carried out by any one discipline alone. New approaches call for areas of the social sciences formerly inactive in cancer research (e.g., anthropology) to contribute the tools and expertise required to address the problems.

Adult

Complete pattern of ocular dominance stripes in V1 of a New World monkey, Cebus apella.

The presence of ocular dominance (OD) stripes in layer IVc of striate cortex (V1) is characteristic of all Old World simians so far studied. In contrast, some species of New World monkeys do not have ocular dominance stripes, and in those that do, the pattern of stripes may be different from that shown in Old World monkeys. This difference has led to the suggestion that OD stripes evolved independently in both groups. We have mapped the entire system of OD stripes in the New World monkey Cebus, by means of cytochrome oxidase histochemistry after monocular enucleation. A striking similarity was found between the patterns in Cebus and Macaca, which is suggestive of common ancestry, rather than parallel evolution.

Animals

Cross-coupled effects of repeated vestibular and optokinetic stimulations on the dynamics of the vestibulo-ocular and optokinetic reflexes in the cat.

Cats were submitted to repeated step stimulations either vestibular or optokinetic. Regardless of which of the two stimuli was used, dynamic modifications were observed in both vestibulo-ocular response and optokinetic after-nystagmus (OKAN). The progressive changes in post-rotational nystagmus and OKAN were quantified by measuring the duration of their primary phase. A parallel evolution of these two parameters was found. When repeated unidirectional vestibular stimulations were used, the same asymmetry was induced in both vestibuloocular responses and OKAN. These results support the hypothesis that the vestibulo-ocular and the optokinetic reflex share a common velocity storage mechanism, although alternative hypotheses cannot be excluded.

Animals