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PubMed1995

Paleopediatrics: or when did human infants really become human?

Modern human children take about twice as long as their closest biological relative, the chimpanzee, to mature. One standard explanation for the evolution of "delayed maturation" at an early stage of human evolution is that it provided the time necessary for immature individuals to learn complex skills, most notably those relating to tool-making abilities. However, after comparing dental maturational profiles of early hominids from South Africa (who apparently did make and use stone tools) (Susman [1994] Science 265:1570-1573) to those of extant humans and chimpanzees, we find no evidence to document an association between "delayed maturation" and tool-making abilities in the early stages of human evolution. This also suggests that the assumed association between prolonged childhood dependency and other behaviors often associated with the advent of tool-making such as cooperative hunting, food sharing, home bases, sexual division of labor, etc., is also suspect. Instead, we must look for other, or additional, selective pressures for the evolution of "delayed maturation," which may postdate the australopithecine radiation.

Animals↗
PubMed2004

Human altruism: economic, neural, and evolutionary perspectives.

Human cooperation represents a spectacular outlier in the animal world. Unlike other creatures, humans frequently cooperate with genetically unrelated strangers, often in large groups, with people they will never meet again, and when reputation gains are small or absent. Experimental evidence and evolutionary models suggest that strong reciprocity, the behavioral propensity for altruistic punishment and altruistic rewarding, is of key importance for human cooperation. Here, we review both evidence documenting altruistic punishment and altruistic cooperation and recent brain imaging studies that combine the powerful tools of behavioral game theory with neuroimaging techniques. These studies show that mutual cooperation and the punishment of defectors activate reward related neural circuits, suggesting that evolution has endowed humans with proximate mechanisms that render altruistic behavior psychologically rewarding.

Altruism↗
PubMed2006

Dynamics, stability and inheritance of somatic DNA methylation imprints.

Recent research highlights the role of CpG methylation in genomic imprinting, histone and chromatin modification, transcriptional regulation, and 'gene silencing' in cancer development. An unresolved issue, however, is the role of stable inheritance of factors that manage epigenetic imprints in renewing or expanding cell populations in soma. Here we propose a mathematical model of CpG methylation that is consistent with the cooperative roles of de novo and maintenance methylation. This model describes (1) the evolution of methylation imprints toward stable, yet noisy equilibria, (2) bifurcations in methylation levels, thus the dual stability of both hypo- and hypermethylated genomic regions, and (3) sporadic transitions from hypo- to hypermethylated equilibria as a result of methylation noise in a finite system of CpG sites. Our model not only affords an explanation of the persistent coexistence of these two equilibria, but also of sporadic changes of site-specific methylation levels that may alter preset epigenetic imprints in a renewing cell population.

Animals↗
PubMed2006

The oxygen transport system in three species of the boreal fish family Gadidae. Molecular phylogeny of hemoglobin.

The Arctic and Antarctic marine faunas differ by age and isolation. Fishes of the two polar regions have undergone different regional histories that have driven the physiological diversities. Antarctic fish are highly stenothermal, in keeping with stable water temperatures, whereas Arctic fish, being exposed to seasonal temperature variations, exhibit higher physiological plasticity. This study reports the characterization of the oxygen transport system of three Arctic species of the family Gadidae, namely the Arctic cod Arctogadus glacialis, the polar cod Boreogadus saida, and the Atlantic cod Gadus morhua. Unlike Antarctic notothenioids, the blood displays high multiplicity, i.e. it has three hemoglobins, similar to many other acanthomorph teleosts. In the most abundant hemoglobin, oxygen binding is modulated by heterotropic effectors, with marked Bohr and Root effects. Remarkably, in two species (A. glacialis and B. saida), the Hill coefficient is very close to one in the whole pH range, indicating the apparent absence of cooperativity. The amino acid sequences have been used to gain insight into the evolution history of globins of polar fish. The results indicate that Arctic and Antarctic globins have different phylogenies and lead us to suggest that the selective pressure of environment stability allows the phylogenetic signal to be maintained in the Antarctic sequences, whereas environmental variability would tend to disrupt this signal in the Gadidae sequences.

Acclimatization↗
PubMed1999

Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their autoinhibitory domains.

The transcription factors Ets-1 and AML1 (the alphaBl subunit of PEBP2/CBF) play critical roles in hematopoiesis and leukemogenesis, and cooperate in the transactivation of the T cell receptor (TCR) beta chain enhancer. The DNA binding capacity of both factors is blocked intramolecularly but can be activated by the removal of negative regulatory domains. These include the exon VII domain for Ets-1 and the negative regulatory domain for DNA binding (NRDB) for alphaB1. Here we report that the direct interaction between the two factors leads to a reciprocal stimulation of their DNA binding activity and activation of their transactivation function. Detailed mapping revealed two independent contact points involving the exon VII and NRDB regions as well as the two DNA binding domains. Using deletion variants and dominant interfering mutants, we demonstrate that the interaction between exon VII and NRDB is necessary and sufficient for cooperative DNA binding. The exon VII and NRDB motifs are highly conserved in evolution yet deleted in natural variants, suggesting that the mechanism described is of biological relevance. The mutual activation of DNA binding of Ets and AML1 through the intermolecular interaction of autoinhibitory domains may represent a novel principle for the regulation of transcription factor function.

Amino Acid Sequence↗
PubMed2001

Mechanisms of T-cell homing to skin.

Although many individual components of the lymphocyte's migratory machinery have been identified and analyzed for function in vitro, interesting questions remain regarding the in vivo integration of these components. How does the lymphocyte "choose" a direction for migration in the complex cytokine/chemokine environment of inflamed dermis when multiple chemokines secreted by multiple cell types are present? Can differences in chemokine expression explain the clinical and histologic differences seen in different inflammatory skin disease? What are the roles of proteins such as VAP-1? Our present understanding of lymphocyte migration has already led to the use of monoclonal antibodies to integrins such as LFA-1 that can potentially be of therapeutic use in skin diseases such as psoriasis. Small molecule inhibitors of T lymphocyte-specific receptors such as CCR4 or CXCR3 are promising agents for controlling T cell-mediated inflammation but have yet to be developed. These receptors may have greater selective expression on skin-homing T cells and thus may decrease the risk of iatrogenic immunosuppression. Close cooperation between the pharmaceutical industry and basic scientists will hopefully lead to the evolution of such compounds and toward more effective treatment of inflammatory skin diseases.

Antibodies, Monoclonal↗
PubMed1998

Mutation and selection within the individual.

Selection within the individual may have played a critical and creative role in evolution, boosting the survival chances of mutations beneficial to the cell and the individual, hindering the spread of deleterious mutations, and reducing the genetic load imposed on the population. We review the literature and present new results to describe the effects of cell-lineage selection on the rate and fixation probability of new mutations. Cell-lineage selection can alter these quantities by several orders of magnitude. Cell-lineage selection is especially important in the case of rare recessive mutations, which are hidden from selection at the individual level but may be exposed to selection at cellular level. Because selection within the individual acts as a sieve eliminating deleterious mutations and increasing the frequency of beneficial ones, mutations observed among progeny will have been pre-selected and are more likely to increase cell proliferation than would randomly generated mutations. Although many authors have focused on the potential conflict between selection at the cellular and individual levels, it must be much more common that the two levels act concordantly. When selection at the cell and individual levels act in a cooperative manner, increased rather than decreased opportunity for germline selection will be favored by evolution.

Animals↗
PubMed1997

Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells.

The transcriptional regulatory elements of many inducible T-cell genes contain adjacent or overlapping binding sites for the Ets and NF-kappaB/NFAT families of transcription factors. Similar arrays of functionally important NF-kappaB/NFAT and Ets binding sites are present in the transcriptional enhancers of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2), suggesting that this pattern of nuclear protein binding sites reflects an evolutionarily conserved mechanism for regulating inducible T-cell gene expression that has been co-opted during HIV evolution. Despite these findings, the molecular mechanisms by which Ets and NF-kappaB/NFAT proteins cooperatively regulate inducible T-cell gene expression remained unknown. In the studies described in this report, we demonstrated a physical interaction between multiple Ets and NF-kappaB/NFAT proteins both in vitro and in activated normal human T cells. This interaction is mediated by the Ets domain of Ets proteins and the C-terminal region of the Rel homology domains of NF-kappaB/NFAT proteins. In addition, the Ets-NF-kappaB/NFAT interaction requires the presence of DNA binding sites for both proteins, as it is abolished by the DNA intercalating agents propidium iodide and ethidium bromide and enhanced by the presence of synthetic oligonucleotides containing binding sites for Ets and NF-kappaB proteins. A dominant-negative mutant of NF-kappaB p50 that binds DNA but fails to interact with Ets proteins inhibits the synergistic activation of the HIV-1 and HIV-2 enhancers by NF-kappaB (p50 + p65) and Ets-1, suggesting that physical interaction between Ets and NF-kappaB proteins is required for the transcriptional activity of the HIV-1 and HIV-2 enhancers. Taken together, these findings suggest that evolutionarily conserved physical interactions between Ets and NF-kappaB/NFAT proteins are important in regulating the inducible expression of T-cell genes and viruses. These interactions represent a potential target for the development of novel immunosuppressive and antiviral therapies.

Base Sequence↗
PubMed1999

Experimental observations of non-Gaussian behavior and stringlike cooperative dynamics in concentrated quasi-two-dimensional colloidal liquids.

We report, from direct observation of particle trajectories as a function of time, the presence of stringlike cooperative motion in a quasi-two-dimensional liquid. We have used digital video microscopy to study the equilibrium dynamics of suspensions of sterically stabilized uncharged poly(methylmethacrylate) spheres confined in a thin glass cell. Our experiments reveal the existence, in semidilute and dense liquid states, of a transition in the qualitative dynamical behavior of the system. At short times particles undergo unhindered Brownian motion, at intermediate times they undergo uncorrelated binary collisions, and at long times these one-particle self-diffusive modes are coupled to collective longitudinal acoustic modes of the fluid, the signature of which is local fluctuating domains of enhanced particle mobility. We study the properties of these domains by examining the density dependence of the van Hove self-correlation function and its deviation from Gaussian behavior. We observe that periods of non-Gaussian behavior correlate precisely with the timing of events involved in the relaxation of "caged" particles and their nearest neighbors. In contrast with relaxation processes in supercooled liquids, the lifetime of dynamical heterogeneities in a dissipative colloidal suspension is found to shift towards shorter time scales with increasing particle density. During time periods for which a quasi-two-dimensional system follows Gaussian behavior, we observe that, as predicted by Cichocki and Felderhof [J. Phys. Condens. Matter 6, 7287 (1994)], the time dependence of the evolution of the effective diffusion coefficient from its short time to its long time value has the form (ln t)/t. This last finding is true for all observed particle densities. To our knowledge, these results are the first experimental verification of the existence of microscopic cooperativity and the predicted temporal evolution of the diffusion coefficient for Brownian motion in concentrated quasi-two-dimensional liquids.

Journal Article↗
PubMed2006

A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon.

KCNQ (KV7) potassium channels underlie subthreshold M-currents that stabilize the neuronal resting potential and prevent repetitive firing of action potentials. Here, antibodies against four different KCNQ2 and KCNQ3 polypeptide epitopes show these subunits concentrated at the axonal initial segment (AIS) and node of Ranvier. AIS concentration of KCNQ2 and KCNQ3, like that of voltage-gated sodium (NaV) channels, is abolished in ankyrin-G knock-out mice. A short motif, common to KCNQ2 and KCNQ3, mediates both in vivo ankyrin-G interaction and retention of the subunits at the AIS. This KCNQ2/KCNQ3 motif is nearly identical to the sequence on NaV alpha subunits that serves these functions. All identified NaV and KCNQ genes of worms, insects, and molluscs lack the ankyrin-G binding motif. In contrast, vertebrate orthologs of NaV alpha subunits, KCNQ2, and KCNQ3 (including from bony fish, birds, and mammals) all possess the motif. Thus, concerted ankyrin-G interaction with KCNQ and NaV channels appears to have arisen through convergent molecular evolution, after the division between invertebrate and vertebrate lineages, but before the appearance of the last common jawed vertebrate ancestor. This includes the historical period when myelin also evolved.

Amino Acid Sequence↗
PubMed1983

Serological evidences for a membrane structure related to human beta 2-microglobulin expressed by certain earthworm leukocytes.

Indirect immunofluorescence performed with 2 polyclonal and 4 monoclonal antibodies directed against human beta 2-microglobulin (beta 2m) revealed the presence of a beta 2m-like determinant on the membrane of a subpopulation of earthworm leukocytes classified as weakly adherent acidophils. Two out of the 4 monoclonal antibodies were found to bind to 15% of the earthworm leukocytes. Similar results were obtained with antibodies specific for beta 2m and isolated by affinity chromatography from either polyclonal antiserum or anti-beta 2m hybridoma supernatant. Additional binding inhibition and competition experiments strengthened the results and suggested that the homology between the structure present on earthworm leukocytes and human beta 2m may be restricted to only one major determinant. The existence of a beta 2m-like molecule in earthworms may provide important clues for understanding protein evolution and basic immune mechanisms.

Animals↗
PubMed1984

Transformation of the Hprt gene with DNA from spermatogenic cells. Implications for the evolution of X chromosome inactivation.

DNA-mediated transformation of hypoxanthine guanine phosphoribosyl transferase (HPRT)-deficient cells was used to assess the state of the chromosome Hprt gene in spermatogenic cells. It had been shown previously that DNA from the inactive X chromosome of somatic cells functions poorly or not at all in HPRT transformation, indicating that DNA modification is involved in somatic cell X chromosome inactivation (XCI). In contrast, DNA from mature sperm does function in HPRT transformation suggesting that DNA modification may not be the basis of XCI in mature sperm. In this paper, transformation of HPRT- mouse and hamster cells has been performed to test the nature of XCI during earlier stages of spermatogenesis. DNA from these developing murine germ cells was shown to be capable of HPRT transformation, extending the observation that XCI in sperm does not appear to involve a DNA modification. We also show here that DNA from mature sperm of marsupials functions in HPRT transformation, a result consistent with a role for sperm XCI in the evolution of somatic X inactivation.

Animals↗
PubMed1991

Dynamics of autocatalytic reaction networks. IV: Inhomogeneous replicator networks.

The inhomogeneous replicator equation is derived as the continuous time model for parallel first and second order autocatalytic replication of macromolecules in a flow reactor based on mass action kinetics. It is shown that the total concentration of replicating material determines the relative importance of the first order and the second order mechanism. A complete description of the dynamics of the first order model and some special features of the inhomogeneous replicator equation are presented. A minimal prebiotic scenario with the potentiality to develop cooperation is derived from the inhomogeneous replicator equation. In this model cooperation can emerge when the total concentration of replication material exceeds a certain threshold. Below this value, a single species is selected; which one is determined by the rate constants of the first order reaction alone. Above this threshold the second order process becomes important and may lead to cooperative behavior such as hypercycles.

Biological Evolution↗
PubMed2002

Correlated response of autogeny to selection for adult starvation resistance in the blowfly, Lucilia cuprina.

We withheld sucrose from adults in three lineages of Lucilia cuprina, producing a four-fold greater mortality than in control lineages, in order to impose direct selection for carbohydrate starvation resistance. The frequency of autogeny (maturation of eggs in the absence of adult protein feeding) increased as a correlated response by an average of 4.9 to 9.2% per generation in three lineages subjected to starvation over five generations. The frequency of autogeny fluctuated but did not display a significant net change in three control lineages. Autogeny in L. cuprina seems to behave as a threshold trait, with a continuous, genetically-based underlying disposition producing discrete phenotypes. The heritability of autogeny in our laboratory lineages was estimated to be 0.09 to 0.39, 0.04 to 0.36, and -0.08 to 0.30 (95% confidence intervals). Despite the potential for autogeny to evolve and despite protein limitation of female fecundity in Australian populations of L. cuprina, the trait is rare or absent in the field. Genetic variation for autogeny may be maintained, but at sub-threshold levels, by nutrient availability in the field, while trade-offs associated with autogeny probably limit the net fitness benefit of the trait and prevent the evolution of a noticeable frequency of autogenous females.

Animals↗