Tissue-Specific Stem Cell Mutation, Selection, and Evolution as a Cause of Aging

There is a mature literature on evolution and aging intended to explain how, despite selection for the morphological, metabolic, physiological, and behavioral prerequisites for survival and procreation, with the passage of time bodies deteriorate ultimately resulting in death. The focus of such explanations is typically on concepts such as age-related variation in the potency of selection and the related notion of antagonistic pleiotropy (Fabian and Flatt, 2011), by which suggests that genes able to promote survival and reproductive success in youth may increase loss of function with age. These concepts address selection on intact organisms. In contrast, a recent article in Science (Goodell and Rando, 2015) contains an article addressing the role of selection directly on somatic cells and in particular tissue-specific stem cells. (more…)

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…)

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…)

Evolution and the Ebola Epidemic. II.

After posting my last commentary on the ongoing Ebola outbreak in West Africa, I listened to the netcast, This Week in Virology (www.twiv.tv), for September 14, 2014.  TWiV sessions, hosted by Vincent Racaniello, a well-known virologist at Columbia University, are generally highly informative, typically offering thoughtful discussions about recently published studies pertaining to viruses or addressing broad areas of virus-related research. (more…)

The Future of the “Selfish Gene” Metaphor

This past December, science writer David Dobbs published an essay (2013) in the online magazine Aeon (aeon.co/magazine/) that purports to explain why the ‘selfish gene’ concept is outmoded and should be retired.  It elicited a good deal of commentary, and in early March, Aeon published responses (Sapolsky et al., 2014) to the original article from four individuals (two scientists, a genetic counselor, and a philosopher) as well as additional comments by Dobbs.  For those who are interested in this controversy, responses to the original Dobbs article were also posted elsewhere by Richard Dawkins (2013) and Jerry Coyne (2013a, b).  Below, I provide a sense of the arguments of Dobbs, the tenor of the criticisms of Dobbs’s piece, and selected other critiques of the gene-centric approach to evolution. (more…)