Adam Richman

Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine

Malaria Sporozoite Vaccine Each year, hundreds of millions of people are infected with Plasmodium falciparum, the mosquito-borne parasite that causes malaria. A preventative vaccine is greatly needed. Seder et al. (p. 1359, published online 8 August; see the Perspective by Good) now report the results from a phase I clinical trial where subjects were immunized intravenously with a whole, attenuated sporozoite vaccine. Three of 9 subjects who received four doses and zero of 6 subjects who received five doses of the vaccine went on to develop malaria after controlled malaria infection. Both antibody titers and cellular immune responses correlated positively with the dose of vaccine received, suggesting that both arms of the adaptive immune response may have participated in the observed protection. Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial. [Also see Perspective by Good] Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine—composed of attenuated, aseptic, purified, cryopreserved PfSPZ—was safe and wel-tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.

Evolution of balanced genetic polymorphism

Extreme genetic polymorphism maintained by balancing selection (so called because many alleles are maintained in a balance by a mechanism of rare allele advantage) is intimately associated with the important task of self/non‐self‐discrimination. Widely disparate self‐recognition systems of plants, animals and fungi share several general features, including the maintenance of large numbers of alleles at relatively even frequency, and persistence of this variation over very long time periods. Because the evolutionary dynamics of balanced polymorphism are very different from those of neutral genetic variation, data on balanced polymorphism have been used as a novel source for inference of the history of populations. This review highlights the unique evolutionary properties of balanced genetic polymorphism, and the use of theoretical understanding in analysis and application of empirical data for inference of population history. However, a second goal of this review is to point out where current theory is incomplete. Recent observations suggest that entirely novel selective forces may act in concert with balancing selection, and these novel forces may be extremely potent in shaping genetic variation at self‐recognition loci.

Correlates of wing morphology with foraging behaviour and migration distance in the genus Phylloscopus

Wing size and shape variation in thirteen species of Old World leaf warblers, genus Phylloscopus, were examined using wing formulae and principal components analysis. Data were taken from male individuals in breeding populations in Northern India and Japan. Species with longer wings migrate further and hover less than species with shorter wings. Species with more pointed wings migrate further and are more arboreal than species with rounder wings. Findings agree with those from previous studies on the genus Phylloscopus. Both foraging behaviour and migration distance have affected wing size and shape evolution in the genus.

EVOLUTION OF BREEDING DISTRIBUTIONS IN THE OLD WORLD LEAF WARBLERS (GENUS PHYLLOSCOPUS)

Among Palearctic warblers of the genus Phylloscopus those species that breed farther north occupy larger geographical ranges than those which breed farther south (Rapoports rule). We suggest that much of this pattern is a consequence of the differential ability of species to occupy areas rendered inhospitable during the Pleistocene. In support of this suggestion, the midpoint of breeding range in a north‐south direction has been an exceptionally labile trait through evolutionary time. Comparisons of ecological attributes of those species breeding in the Himalayas with close relatives in Siberia implies a role for habitat tracking in determining which species have been able to colonize northern areas; hypotheses based on climate and climatic variability have less support. In addition there is a likely role for geographic barriers and/or biotic interactions in preventing some taxa from spreading from small southern ranges.

Reptilian Extinctions Over the Last Ten Thousand Years

The fossil record of the earth shows that faunal and floral extinctions increased dramatically during certain periods. These “paleo” upheavals like those at the end of Permian and Cretaceous have long provided the punctuations that geologists and paleontologists use to divide the geological periods. A challenging question in conservation science is whether the processes affecting extinction rates today are helpful in interpreting extinction in the past and, conversely, whether prehistoric extinctions are useful for understanding recent extinctions.

The Imprint of History on Communities of North American and Asian Warblers

The ecology of the component species of an adaptive radiation is likely to be influenced by the form of the founding ancestor to the radiation, its timing, and rates of speciation and extinction. These historical features complement environmental selection pressures. They imply that, if the history of the species’ radiations are very different, ecological communities are unlikely to be completely convergent even when placed in identical environments. We compare the adaptive radiation of the Dendroica warblers of North America with that of the Phylloscopus warblers of Asia. We consider the ecology of the species in two localities where species’ diversity is very high (New Hampshire, U.S.A., and Kashmir, India, respectively) and contrast the history of the two radiations on the basis of a molecular (mitochondrial cytochrome b) phylogeny. By comparison with the Phylloscopus, the Dendroica are on average larger and morphologically more similar to one another. Although there is some similarity between the Dendroica and Phylloscopus communities, they differ in foraging behavior and in associations of morphology with ecological variables. The Dendroica likely reflect an early Pliocene radiation and are two to four times younger than the Phylloscopus. They probably had a colorful sexually dichromatic ancestor, implicating sexual selection in the production of the many ecologically similar species. The Phylloscopus are much older and probably had a drab, monomorphic ancestor. Given the difference in ages of the two radiations, it is plausible that the close species’ packing of the Dendroica warblers is a transient phenomenon. If this is the case, community structure evolves on the timescales of millions of years. Differences in ancestry and timing of the species’ radiations can be related to the different biogeography of the two regions. This implies that the historical imprint on adaptive radiations could be predicted on the basis of the attributes of ancestors and biogeographical context.

S -allele sequence diversity in natural populations of Solanum carolinense (Horsenettle)

S-allele diversity in Solanum carolinense was surveyed in two natural populations, located in Tennessee and North Carolina, with a molecular assay to determine the genotype of individual plants. A total of 13 different S-alleles were identified and sequenced. There is high overlap between the two populations sampled, with 10 alleles shared in common, one allele found only in Tennessee, and two found only in North Carolina. The number of alleles in this species appears to be extremely low compared with other species with gametophytic self-incompatibility. Sequence comparisons show that most alleles are extremely different one from another in their primary sequence and a phylogenetic analysis indicates extensive trans-specific evolution of S-lineages. In addition, some alleles appear to be derived much more recently. The implications of these observations are discussed in the light of recent theoretical results on S-allele population diversity and persistence.

Relative roles of mutation and recombination in generating allelic polymorphism at an MHC class II locus in Peromyscus maniculatus

The MHC class II loci encoding cell surface antigens exhibit extremely high allelic polymorphism. There is considerable uncertainty in the literature over the relative roles of recombination and de novo mutation in generating this diversity. We studied class II sequence diversity and allelic polymorphism in two populations of Peromyscus maniculatus, which are among the most widespread and abundant mammals of North America. We find that intragenic recombination (or gene conversion) has been the predominant mode for the generation of allelic polymorphism in this species, with the amount of population recombination per base pair exceeding mutation by at least an order of magnitude during the history of the sample. Despite this, patchwork motifs of sites with high linkage disequilibrium are observed. This does not appear to be consistent with the much larger amount of recombination versus mutation in the history of the sample, unless the recombination rate is highly non-uniform over the sequence or selection maintains certain sites in linkage disequilibrium. We conclude that selection is most likely to be responsible for preserving sequence motifs in the presence of abundant recombination.

Learning from rejection: the evolutionary biology of single-locus incompatibility

The self-incompatibility (S-) locus of flowering plants is among the most polymorphic known. PCR methods can now be used to estimate both the number of alleles in natural populations and their sequence diversity. The number of alleles provides an estimate of recent effective population size, thus the S-locus provides a tool for examining how species characteristics affect population size. Sequence relationships among alleles provide another estimate of population size extending millions of years into the past. Relationships between S-alleles and related genes provide a means of dating the age of origin of incompatibility systems and determining which, if any, angiosperm families share incompatibility by homology.

ECOLOGICAL DIVERSIFICATION AND COMMUNITY STRUCTURE IN THE OLD WORLD LEAF WARBLERS (GENUS PHYLLOSCOPUS) : A PHYLOGENETIC PERSPECTIVE

I investigated the historical basis for variation in regional species diversity. I used a molecular phylogenetic analysis within a single genus of birds (the Old World leaf warblers, genus Phylloscopus) in conjunction with ecological studies in Europe, the Himalayas, and Japan to evaluate the importance of historical events in shaping the present constellation of morphology and behavior in the three different regions. The relatively depauperate assemblages have different histories. In Japan, there was invasion of several lineages, which have more closely related species elsewhere in Asia, whereas in Europe there was also limited in situ speciation. Much of the structure of peripheral communities is attributable to invasions from species‐rich Asia, with little in situ morphological diversification. Within the Phylloscopus there are several phylogenetic clades with nonoverlapping size distributions. Major ecological and morphological shifts occurred early in the history of diversification within the group, and rarely since.