GENETICS/ENVIRONMENT
Explaining how interactions between genes and the environment influence social behavior is a fundamental research goal, yet there is limited relevant information for species exhibiting natural variation in social organization. The fire ant Solenopsis invicta is characterized by a remarkable form of social polymorphism, with the presence of one or several queens per colony and the expression of other phenotypic and behavioral differences being completely associated with allelic variation at a single Mendelian factor marked by the gene Gp-9. Microarray analyses of adult workers revealed that differences in the Gp-9 genotype are associated with the differential expression of an unexpectedly small number of genes, many of which have predicted functions, implying a role in chemical communication relevant to the regulation of colony queen number. Even more surprisingly, worker gene expression profiles are more strongly influenced by indirect effects associated with the Gp-9 genotypic composition within their colony than by the direct effect of their own Gp-9 genotype. This constitutes an unusual example of an "extended phenotype" and suggests a complex genetic architecture with a single Mendelian factor, directly and indirectly influencing the individual behaviors that, in aggregate, produce an emergent colony-level phenotype.
- Wang J, Ross KG, Keller L (2008) Genome-Wide Expression Patterns and the Genetic Architecture of a Fundamental Social Trait. PLoS Genet 4(7): e1000127. doi:10.1371/journal.pgen.1000127
COMPUTATIONAL BIOLOGY
Innovation in computational biology research is predicated on the availability of published methods and computational resources. These resources facilitate the generation of new hypotheses and observations both on the part of the creators and the scientists who use them. These methods and resources include Web servers, databases, and software, both complex and simple, that implement a specific procedure or algorithm. Usually, a resource is maintained by the laboratory in which it was initially developed. We would assert that there is a growing level of frustration among scientists who attempt to use many of these resources and find that they no longer exist or are not properly maintained. Whether you agree or disagree with this statement and the evidence that follows, we welcome your thoughts and invite you to add a Comment to this article to share your own experiences and perspectives.
It is timely to visit this situation in more detail. The International Society for Computational Biology (ISCB) is reviewing its position on software sharing, and this journal is now doing the same (the views expressed here are not necessarily those of the journal-this is a personal perspective and not an editorial). To help us gain a better understanding of the resource situation, we took on two simple experiments: first, a review of the persistence of Web servers, and, second, an experience creating a metaserver-a Web site where users can come and run a variety of methods to compare results. Here is what we found.
- Veretnik S, Fink JL, Bourne PE (2008) Computational Biology Resources Lack Persistence and Usability. PLoS Comput Biol 4(7): e1000136. doi:10.1371/journal.pcbi.1000136
IMMUNOLOGY
Recent data suggest that Nef-mediated downmodulation of TCR-CD3 may protect SIVsmm-infected sooty mangabeys (SMs) against the loss of CD4+ T cells. However, the mechanisms underlying this protective effect remain unclear. To further assess the role of Nef in nonpathogenic SIV infection, we cloned nef alleles from 11 SIVsmm-infected SMs with high (>500) and 15 animals with low (<500) CD4+ T-cells/µl in bulk into proviral HIV-1 IRES/eGFP constructs and analyzed their effects on the phenotype, activation, and apoptosis of primary T cells. We found that not only efficient Nef-mediated downmodulation of TCR-CD3 but also of MHC-I correlated with preserved CD4+ T cell counts, as well as with high numbers of Ki67+CD4+ and CD8+CD28+ T cells and reduced CD95 expression by CD4+ T cells. Moreover, effective MHC-I downregulation correlated with low proportions of effector and high percentages of naïve and memory CD8+ T cells. We found that T cells infected with viruses expressing Nef alleles from the CD4low SM group expressed significantly higher levels of the CD69, interleukin (IL)-2 and programmed death (PD)-1 receptors than those expressing Nefs from the CD4high group. SIVsmm Nef alleles that were less active in downmodulating TCR-CD3 were also less potent in suppressing the activation of virally infected T cells and subsequent cell death. However, only nef alleles from a single animal with very low CD4+ T cell counts rendered T cells hyper-responsive to activation, similar to those of HIV-1. Our data suggest that Nef may protect the natural hosts of SIV against the loss of CD4+ T cells by at least two mechanisms: (i) downmodulation of TCR-CD3 to prevent activation-induced cell death and to suppress the induction of PD-1 that may impair T cell function and survival, and (ii) downmodulation of MHC-I to reduce CTL lysis of virally infected CD4+ T cells and/or bystander CD8+ T cell activation.
- Schindler M, Schmökel J, Specht A, Li H, Münch J, et al. (2008) Inefficient Nef-Mediated Downmodulation of CD3 and MHC-I Correlates with Loss of CD4+ T Cells in Natural SIV Infection. PLoS Pathog 4(7): e1000107. doi:10.1371/journal.ppat.1000107
