Darwinian selection on a selfing locus

The shift to self-pollination is one of the most prevalent evolutionary transitions in flowering plants. In the selfing plant Arabidopsis thaliana, pseudogenes at the SCR and SRK self-incompatibility loci are believed to underlie the evolution of self-fertilization. Positive directional selection has driven the evolutionary fixation of pseudogene alleles of SCR, leading to substantially reduced nucleotide variation. Coalescent simulations indicate that this adaptive event may have occurred very recently and is possibly associated with the post-Pleistocene expansion of A. thaliana from glacial refugia. This suggests that ancillary morphological innovations associated with self-pollination can evolve rapidly after the inactivation of the self-incompatibility response.     

Evidence for a one-allele assortative mating locus

Theoretical models have shown that speciation with gene flow can occur readily via a "one-allele mechanism," where the spread of the same allele within both of two diverging species reduces their subsequent hybridization. Here we present direct genetic evidence for such an allele in Drosophila pseudoobscura. Alleles conferring high or low assortative mating in D. pseudoobscura produce the same effects when inserted into D. persimilis. This observation suggests that the type of genetic variation that is most conducive to controversial modes of speciation with gene flow, such as reinforcement or sympatric speciation, is present in nature.     

Characterization of a common susceptibility locus for asthma-related traits

Susceptibility to asthma depends on variation at an unknown number of genetic loci. To identify susceptibility genes on chromosome 7p, we adopted a hierarchical genotyping design, leading to the identification of a 133-kilobase risk-conferring segment containing two genes. One of these coded for an orphan G protein-coupled receptor named GPRA (G protein-coupled receptor for asthma susceptibility), which showed distinct distribution of protein isoforms between bronchial biopsies from healthy and asthmatic individuals. In three cohorts from Finland and Canada, single nucleotide polymorphism-tagged haplotypes associated with high serum immunoglobulin E or asthma. The murine ortholog of GPRA was up-regulated in a mouse model of ovalbumin-induced inflammation. Together, these data implicate GPRA in the pathogenesis of atopy and asthma.     

Evolutionarily assembled cis-regulatory module at a human ciliopathy locus

Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.     

Genetic mapping of a murine leukemia virus-inducing locus of AKR mice

The chromosomal location of one of the two murine leukemia virus-inducing loci of AKR mice has been determined. The locus, which appears to be the integrated genome of the virus, is designated Akv-1, and is on linkage group 1, 12 map units from Gpi-1, with gene order c-Gpi-1-Akv-1. This identification of a closely linked gene whose phenotype is independent of virus expression should facilitate analysis of the biologic importance of the Akv-1 locus.     

Evolution of a protein fold in vitro

A "switch" mutant of the Arc repressor homodimer was constructed by interchanging the sequence positions of a hydrophobic core residue, leucine 12, and an adjacent surface polar residue, asparagine 11, in each strand of an intersubunit beta sheet. The mutant protein adopts a fold in which each beta strand is replaced by a right-handed helix and side chains in this region undergo significant repacking. The observed structural changes allow the protein to maintain solvent exposure of polar side chains and optimal burial of hydrophobic side chains. These results suggest that new protein folds can evolve from existing folds without drastic or large-scale mutagenesis.     

Evolution of a nitrogen atmosphere on titan

Photochemical calculations indicate that if NH(3) outgassed from Titan it should have been converted to a dense N(2) atmosphere during the lifetime of the satellite. A crucial step in the process involves a gas phase reaction of N(2)H(4) with H. The most favorable conditions for this step would be the intermediate production of a CH(4)-H(2) greenhouse capable of raising the gas temperature to 150 degrees K. Subsequently about 20 bars of N(2) could have evolved. The pressure-induced opacity of 20 bars of N(2) should suffice to explain the recently measured 200 degrees K surface temperature. Unlike the situation on Jupiter, NH(3) is not recycled on Titan by reactions involving N(2) or N(2)H(4). This may explain the failure of recent attempts to detect NH(3) in the upper atmosphere of Titan.     

Evolution of a vertebrate social decision-making network

Animals evaluate and respond to their social environment with adaptive decisions. Revealing the neural mechanisms of such decisions is a major goal in biology. We analyzed expression profiles for 10 neurochemical genes across 12 brain regions important for decision-making in 88 species representing five vertebrate lineages. We found that behaviorally relevant brain regions are remarkably conserved over 450 million years of evolution. We also find evidence that different brain regions have experienced different selection pressures, because spatial distribution of neuroendocrine ligands are more flexible than their receptors across vertebrates. Our analysis suggests that the diversity of social behavior in vertebrates can be explained, in part, by variations on a theme of conserved neural and gene expression networks.     

Evolution of a polyphenism by genetic accommodation

Polyphenisms are adaptations in which a genome is associated with discrete alternative phenotypes in different environments. Little is known about the mechanism by which polyphenisms originate. We show that a mutation in the juvenile hormone-regulatory pathway in Manduca sexta enables heat stress to reveal a hidden reaction norm of larval coloration. Selection for increased color change in response to heat stress resulted in the evolution of a larval color polyphenism and a corresponding change in hormonal titers through genetic accommodation. Evidently, mechanisms that regulate developmental hormones can mask genetic variation and act as evolutionary capacitors, facilitating the origin of novel adaptive phenotypes.     

A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus

Bacterial pathogens frequently use protein secretion to mediate interactions with their hosts. Here we found that a virulence locus (HSI-I) of Pseudomonas aeruginosa encodes a protein secretion apparatus. The apparatus assembled in discrete subcellular locations and exported Hcp1, a hexameric protein that forms rings with a 40 angstrom internal diameter. Regulatory patterns of HSI-I suggested that the apparatus functions during chronic infections. We detected Hcp1 in pulmonary secretions of cystic fibrosis (CF) patients and Hcp1-specific antibodies in their sera. Thus, HSI-I likely contributes to the pathogenesis of P. aeruginosa in CF patients. HSI-I-related loci are widely distributed among bacterial pathogens and may play a general role in mediating host interactions.     

Cloning of breakpoints of a chromosome translocation identifies the AN2 locus

Chromosome translocations involving 11p13 have been associated with familial aniridia in two kindreds highlighting the chromosomal localization of the AN2 locus. This locus is also part of the WAGR complex (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation). In one kindred, the translocation is associated with a deletion, and probes for this region were used to identify and clone the breakpoints of the translocation in the second kindred. Comparison of phage restriction maps exclude the presence of any sizable deletion in this case. Sequences at the chromosome 11 breakpoint are conserved in multiple species, suggesting that the translocation falls within the AN2 gene.     

Mini-mouse: disruption of the pygmy locus in a transgenic insertional mutant

A founder transgenic mouse harbored two different integration patterns of a transgene at the same locus, each of which gave rise to a similar autosomal recessive mutation. Mice of the mutant phenotype were of small stature but had normal levels of growth hormone. The disrupted locus was cloned, and a genetic and molecular analysis showed that the insertional mutants were allelic to a spontaneous mutant, pygmy. The mice should be a useful model for the growth hormone-resistant human dwarf syndromes and could lead to a greater understanding of the pathways involved in growth and development.     

Genetic mapping of Ir locus in man: linkage to second locus of HL-A

Fifty-seven members of a family that spanned three generations were studied for antigen E and ragweed skin sensitivity and HL-A antigens. There was significant association between the haplotype HL-A 2-12 and antigen E skin hypersensitivity (F = .22 to .26) in this family. The map order is first locus of HL-A, second locus of HL-A, and IrE. These determinants are considered to be part of the linkage group HL-1.     

Evolution of virulence in a plant host-pathogen metapopulation

In a wild plant-pathogen system, host resistance and pathogen virulence varied markedly among local populations. Broadly virulent pathogens occurred more frequently in highly resistant host populations, whereas avirulent pathogens dominated susceptible populations. Experimental inoculations indicated a negative trade-off between spore production and virulence. The nonrandom spatial distribution of pathogens, maintained through time despite high pathogen mobility, implies that selection favors virulent strains of Melampsora lini in resistant Linum marginale populations and avirulent strains in susceptible populations. These results are consistent with gene-for-gene models of host-pathogen coevolution that require trade-offs to prevent pathogen virulence increasing until host resistance becomes selectively neutral.     

MAP kinase phosphatase as a locus of flexibility in a mitogen-activated protein kinase signaling network

Intracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein kinase C (PKC) system is one such network that regulates many cellular machines, including the cell cycle machinery and autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis and experiments in mouse NIH-3T3 fibroblasts to understand the design principles of this controller network. We find that the growth factor-stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states. At low concentrations of MAPK phosphatase, the system exhibits bistable behavior, such that brief stimulus results in sustained MAPK activation. The MAPK-induced increase in the amounts of MAPK phosphatase eliminates the prolonged response capability and moves the network to a monostable state, in which it behaves as a proportional response system responding acutely to stimulus. Thus, the MAPK 1, 2/PKC controller network is flexibly designed, and MAPK phosphatase may be critical for this flexible response.     

Characterization of dwarf mutants and molecular mapping of a dwarf locus in soybean

Plant height is one of the most important traits in soybean. The semi-dwarf soybean cultivars could improve the ability of lodging resistance to obtain higher yield. To broaden the dwarfism germplasm resources in soybean, 44 dwarf mutants were identified from a gamma rays mutagenized M_-2 population. Two of these mutants, Gmdwf1(Glycine max dwarf 1) and Gmdwf2(Glycine max dwarf 2), were investigated in this study. Genetic analysis showed that both mutants were inherited in a recessive manner and their mutated regions were delimited to a 2.610-Mb region on chromosome 1 by preliminary mapping. Further fine mapping study proved that the two mutants had a common deletion region of 1.552 Mb in the target region, which was located in a novel locus site without being reported previously. The dwarfism of Gmdwf1 could not be rescued by gibberellin(GA) and brassinolide(BR) treatments, which indicated that the biosynthesis of these hormones was not deficient in Gmdwf1.     

Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila

Potassium currents are crucial for the repolarization of electrically excitable membranes, a role that makes potassium channels a target for physiological modifications that alter synaptic efficacy. The Shaker locus of Drosophila is thought to encode a K+ channel. The sequence of two complementary DNA clones from the Shaker locus is reported here. The sequence predicts an integral membrane protein of 70,200 daltons containing seven potential membrane-spanning sequences. In addition, the predicted protein is homologous to the vertebrate sodium channel in a region previously proposed to be involved in the voltage-dependent activation of the Na+ channel. These results support the hypothesis that Shaker encodes a structural component of a voltage-dependent K+ channel and suggest a conserved mechanism for voltage activation.