Population genetic analysis of autophagy and phagocytosis genes in Drosophila melanogaster and D. simulans.

Autophagy and phagocytosis are cellular immune mechanisms for internalization and elimination of intracellular and extracellular pathogens. Some pathogens have evolved the ability to inhibit or manipulate these processes, raising the prospect of adaptive reciprocal co-evolution by the host. We performed population genetic analyses on phagocytosis and autophagy genes in Drosophila melanogaster and D.

Comparative transcriptomics reveals CrebA as a novel regulator of infection tolerance in D. melanogaster.

Host responses to infection encompass many processes in addition to activation of the immune system, including metabolic adaptations, stress responses, tissue repair, and other reactions. The response to bacterial infection in Drosophila melanogaster has been classically described in studies that focused on the immune response elicited by a small set of largely avirulent microbes. Thus, we have surprisingly limited knowledge of responses to infection that are outside the canonical immune response, of how the response to pathogenic infection differs from that to avirulent bacteria, or even of how generic the response to various microbes is and what regulates that core response.

The Toll pathway underlies host sexual dimorphism in resistance to both Gram-negative and Gram-positive bacteria in mated Drosophila.

Background: Host sexual dimorphism is being increasingly recognized to generate strong differences in the outcome of infectious disease, but the mechanisms underlying immunological differences between males and females remain poorly characterized. Here, we used Drosophila melanogaster to assess and dissect sexual dimorphism in the innate response to systemic bacterial infection.

Results: We demonstrated sexual dimorphism in susceptibility to infection by a broad spectrum of Gram-positive and Gram-negative bacteria.

Genetics and regulatory impact of alternative polyadenylation in human B-lymphoblastoid cells.

Gene expression varies widely between individuals of a population, and regulatory change can underlie phenotypes of evolutionary and biomedical relevance. A key question in the field is how DNA sequence variants impact gene expression, with most mechanistic studies to date focused on the effects of genetic change on regulatory regions upstream of protein-coding sequence. By contrast, the role of RNA 3'-end processing in regulatory variation remains largely unknown, owing in part to the challenge of identifying functional elements in 3' untranslated regions.

Negative feedback confers mutational robustness in yeast transcription factor regulation.

Organismal fitness depends on the ability of gene networks to function robustly in the face of environmental and genetic perturbations. Understanding the mechanisms of this stability is one of the key aims of modern systems biology. Dissecting the basis of robustness to mutation has proven a particular challenge, with most experimental models relying on artificial DNA sequence variants engineered in the laboratory.