The Evolution & Medicine Review

Altered Androgen Receptor Ligand Specificity in Prostate Cancer Cells Treated with an Androgen Biosynthesis Inhibitor

Carcinomas of the prostate are the most common cancers affecting men and a leading cause of male cancer deaths in the United States (CDC web site, Cancer Prevention and Control).  Given the unique association of the prostate with males, it makes sense that prosate carcinoma cells are often dependent for continued growth and proliferation on signaling by the androgen receptor, as andogens are primarily associated with physiological effects critical for male sexual development.  Therefore, therapies aimed at inhibiting either androgen synthesis or androgen receptor function make great sense. In a recent paper by Chen et al. (2014), Steven Balk and colleagues demonstrate that treatment of castration-resistant prostate cancer with a drug (abiraterone) that inhibits the production of androgens can select for mutant androgen receptors (AR) that more effectively recognize and get activated by a non-androgen. (more…)

Putting the Kill in “Shock and Kill”: Overcoming Evolutionary Obstacles to HIV Cure

According to estimates by the World Health Organization, in 2013 on the order of 35 million people were infected with HIV worldwide (http://www.who.int/gho/hiv/en/).  Globally, about 1.5 million people are believed to have died from AIDS-related diseases in that year.  Substantial, although perhaps not insurmountable, obstacles to the development of a highly effective vaccine for HIV-1 have increased interest in curative strategies.  A key challenge to cure strategies is that infected people harbor a latent reservoir of infected CD4+ memory T cells that do not express significant amounts of viral proteins.  The paucity of viral proteins in these cells makes it more difficult to identify infected cells and eradicate them.  A new study (Deng et al., 2015) in Nature from Robert Siliciano’s lab at Johns Hopkins identifies an additional difficulty faced by one of the currently popular approaches to curative therapy but also, more optimistically, suggests a way to overcome this challenge. (more…)

Cellular ‘Gold’: Competition for Iron as the Cause of Reciprocal Positive Selection of Host and Pathogen Iron-Binding Proteins

Iron is a critical metal for essential cellular processes, such as respiration, in both human and microbial cells.  Thus, in the context of infection, iron is a high-value cellular commodity and an evolutionist might reasonably expect a metallic tug-of-war between host and pathogen iron-binding proteins or other iron-binding molecules (siderophores).  This speculation is impressively supported in a paper published this month (Barber and Elde, 2014).  These authors provide strong evidence for positive selection affecting several sites in host (transferrin, Tf) and pathogen (transferrin binding protein A) iron-binding proteins based on a combination of genetic, structural, and functional experimental methods. (more…)

Eukaryotic Exploitation of Bacterial Anti-Microbial Genes via Trans-Kingdom Horizontal Gene Transfer

 

An article published online at the Nature web site on November 24 (Chou et al., 2014) presents a fascinating study of examples in which bacterial genes have found their way to a number of distinct eukaryotic lineages including ticks and mites, gastropod (e.g., snails and slugs) and bivalve mollusks (e.g. clams and oysters), and choanoflagellates (a subset of ptotozoans).  Type VI secretion amidase effector (Tae) molecules (encoded by tae genes) can kill rival bacteria by degrading their cells walls when delivered into those competing cells.  The eukaryotes cited above all have “domesticated amidase effectors” (dae) genes, all of which are extremely similar to one of the four extant bacterial tae genes.  Of the four tae genes found in bacterial species, three have been transferred to one or another eukaryotic genome. (more…)

Wrong with Geschwind?: Dubious Ideas About Autism and Human Evolution

 

Recently, I heard the latter portions of the radio version of a play, “Lucy” by Damien Atkins, relating to autism and produced by L.A. Theatre Works.  “Lucy” was originally performed and reviewed as long ago as November of 2007, but I was not aware of it until I encountered the production for radio about one week ago.  The plot revolves around a couple (Vivian and Gavin) with a daughter (Lucy) who is 13 years old and has a severe form of autism.  Of particular interest for the EMR readership is how Lucy’s mother, Vivian, views the relationship between the direction of human evolution and the prevalence of autism and the need for individuals with autism to receive therapy. (more…)