Antigenic mapping of a human λ light chain: Correlation with three dimensional structure

Although the amino acid sequence and three-dimensional structure of human immunoglobulin light chains have been known for more than 15 years, the location of antigenic markers characteristic of chains has not been determined. Here, we use a set of synthetic overlapping peptides to completely model the sequence of the chain Mcg and test these for the binding or rabbit and goat antisera specific for chain determinants. We assess peptide contributions to -antigenic reactivity and also to identify a portion of C-region where conformational factors contribute to the antigenicity. Specific determinants occur both in the constant and variable (first and third framework) domains of the molecule. The fourth framework of the variable region, a segment specified by the joining gene, is also recognized and cross-reacts antigenically with the homologous region of T cell receptor chains. Major specific determinants are localized in the N- and C-terminal segments, which are linear and devoid of major conformational folding. Other segments that are strongly antigenic, such as the third framework of the V region (residue 78–93) and a segment of the constant region (residues 177–192), show strong conformational dependence in antigenicity.     

ON THE LOW HERITABILITY OF LIFE-HISTORY TRAITS

Life-history traits such as longevity and fecundity often show low heritability. This is usually interpreted in terms of Fisher's fundamental theorem to mean that populations are near evolutionary equilibrium and genetic variance in total fitness is low. We develop the causal relationship between metric traits and life-history traits to show that a life-history trait is expected to have a low heritability whether or not the population is at equilibrium. This is because it is subject to all the environmental variation in the metric traits that affect it plus additional environmental variation. There is no simple prediction regarding levels of additive genetic variance in life-history traits, which may be high at equilibrium. Several other patterns in the inheritance of life-history traits are readily predicted from the causal model. These include the strength of genetic correlations between life-history traits, levels of nonadditive genetic variance, and the inevitability of genotype-environment interaction.     

Bone Growth Dynamics of the Facial Skeleton and Mandible in <Emphasis Type="Italic">Gorilla gorilla</Emphasis> and <Emphasis Type="Italic">Pan troglodytes</Emphasis>

Adult craniofacial morphology results from complex processes that involve growth by bone modelling and interactions of skeletal components to keep a functional and structural balance. Previous analyses of growth dynamics in humans revealed critical changes during late ontogeny explaining particular morphological features in our species. Data on bone modelling patterns from other primate species could help us to determine whether postnatal changes in the growth dynamics of the craniofacial complex are human specific or are shared with other primates. However, characterizations of bone modelling patterns through ontogeny in non-human hominids are scarce and restricted to isolated data on facial and mandibular regions. In the present study, we analyse the bone modelling patterns in an ontogenetic series of Pan and Gorilla to infer the growth dynamics of their craniofacial complex during postnatal development. Our results show that both Pan troglodytes and Gorilla gorilla are characterized by species-specific bone modelling patterns indicative of a mainly forward growth direction during postnatal development. Both species show minor but consistent ontogenetic changes in the distribution of bone modelling fields in specific regions of the face and mandible, in contrast to other regions which show more constant bone modelling patterns. In addition, we carry out a preliminary integrative study merging histological and geometric morphometric data. Both approaches yield highly complementary data, each analysis providing details on specific growth dynamics unavailable to the other. Moreover, geometric morphometric data show that ontogenetic variation in the modelling pattern of the mandibular ramus may be linked to sexual dimorphism.     

Predators favour mimicry in a tropical reef fish

Batesian mimicry evolves when the 'umbrella' of protection provided by resemblance to a conspicuous unpalatable model species is sufficient to overcome increased predation risk associated with greater conspicuousness. However, the shape and extent of this umbrella, that is, how the level of protection provided by mimicry changes with degree of resemblance between model and mimic, is poorly known. We investigated the response of wild predatory fishes to plastic replicas of a model-mimic species pair of tropical reef fishes, Canthigaster valentini (a toxic pufferfish, the model) and Paraluteres prionurus (the putative mimic), and additional replicas with progressively lower degrees of resemblance to the mimic species. Our results reveal a relatively broad region of protection, indicated by a reduced approach rate by piscivorous fishes, surrounding the colour pattern of the model species. Protection increased with increasing resemblance. By contrast, the response of non-piscivorous fishes was unrelated to degree of resemblance of replicas to the model. Our results suggest that piscivorous fishes on the reef are educated regarding the toxicity of C. valentini, and that avoidance of fish having the pufferfish colour pattern has generated selection favouring mimetic resemblance by the palatable P. prionurus. The relatively broad protective umbrella has probably facilitated the initial evolution of resemblance in the palatable prey species despite the potential hazards of greater conspicuousness.     

Frequency dependent natural selection during character displacement in sticklebacks

Abstract We know little about how natural selection on a species is altered when a closely related species consuming similar resources appears in its environment. In a pond experiment with threespine sticklebacks I tested the prediction that divergent natural selection between competitors is frequency-dependent, changing with the distribution of phe-notypes in the environment. Differential growth and survival of phenotypes in a target stickleback population were contrasted between two treatments. In one treatment an offshore zooplankton feeder (the limnetic stickleback species) was added to the same pond as the target. In the other treatment I added the benthic stickleback instead, a species adapted to feeding on invertebrates from sediments and inshore vegetation. The target population was ecologically and morphologically intermediate with phenotypic variance artificially inflated by hybridization. Growth rates of phenotypes within the target population differed between treatments as predicted by character displacement. The impact of adding a second species always fell most heavily on those phenotypes in the target population resembling the added species most closely. However, those individuals in the target population that most resembled the added species did not experience reduced survival. Instead, consistent survival differences between populations suggested the presence of an inshore –offshore gradient in mortality risk. These results provide further support for the hypothesis of character displacement in sympatric sticklebacks. They suggest that displacement along the resource gradient also led to divergence in vulnerability to agents of mortality, probably including predation.     

Structural,antigenic and evolutionary analyses of immunoglobulins and T cell receptors

We have had the pleasure of collaborating with Allen Edmundson for the past 15 years on the structure, binding properties and evolution of immunoglobulins and T cell receptors. Among the most significant contributions of our joint efforts were: (1) the predictive use of structural features of immunoglobulin domains to model the three-dimensional structures of the immunoglobulin domains of human T-cell receptor alpha and beta chains as well as shark light chains and V(H) domains; (2) the finding that normal humans and other vertebrates express autoantibodies against combining site epitopes of their own T cell receptors; (3) the mapping of the peptide autoepitopes recognized in health, autoimmunity and retroviral infection; and (4) the determination that epitope recognition promiscuity is a characteristic property of the combining sites of IgM immunoglobulins ranging from those of sharks to those of humans. We briefly review the salient findings and status of these studies and indicate the future directions that we will pursue in their continuation.     

Natural autoantibodies to TCR public idiotopes: potential roles in immunomodulation.

Autoantibodies directed against variable domain epitopes of the alpha/beta T cell receptor (TCR) occur in sera of man, mouse and other vertebrates. Here, we focus upon autoantibodies expressed in human rheumatoid arthritis (RA) and systemic erythematosus (SLE) with parallel studies involving collagen induced arthritis (CIA) in mice transgenic for human HLA-DR conferring resistance or susceptibility to autoimmune disease. We report specificity characterization of polyclonal and monoclonal IgM and IgG autoantibodies from SLE and for IgM monoclonal autoantibodies of RA patients. The data suggests that autoantibodies directed against "public" idiotopes present in the first complementarity determining region (CDR1) and the third framework (FR3) of the Vbeta gene products are generated in response to over-production of autodestructive T cells bearing particular Vbeta gene products and function to modulate (downregulate) the expression of these T cells. Since antibodies of these specificities are present in polyclonal IgG immunoglobulin (IVIG) preparations used for therapeutic purposes, the immunomodulatory effects of antibodies directed against TCR variable domains may account, at least in part, for the efficacy of IVIG preparations in therapy of autoimmune diseases and in the prevention of graft versus host reactions.     

Ecology and the origin of species

The ecological hypothesis of speciation is that reproductive isolation evolves ultimately as a consequence of divergent natural selection on traits between environments. Ecological speciation is general and might occur in allopatry or sympatry, involve many agents of natural selection, and result from a combination of adaptive processes. The main difficulty of the ecological hypothesis has been the scarcity of examples from nature, but several potential cases have recently emerged. I review the mechanisms that give rise to new species by divergent selection, compare ecological speciation with its alternatives, summarize recent tests in nature, and highlight areas requiring research.