Prions, Pathology, and the Promotion of Propitious Phenotypes

A prion is a protein that can adopt a conformation other than the ‘standard’ functional conformation and this alternative conformation favors self-association. The aggregation-associated conformation can then be imposed on additional copies of the protein in the original conformation.  This self-templating mechanism for propagation is known primarily for causing neurodegenerative conditions in humans and in animals, such as kuru or Creutzfeldt-Jakob disease in humans or bovine spongiform encephalopathy (i.e., mad cow disease) in cattle.  Since this process of converting protein conformations can be transmitted from one animal to another or one person to another by some routes, such as cannibalism in the case of kuru, the name prion was created to indicate an infectious protein particle.  This concept of an infectious agent that involved no nucleic acid was the basis for the Nobel Prize in Physiology or Medicine awarded to Stanley Prusiner in 1997 (http://www.nobelprize.org/nobel_prizes/medicine/laureates/1997/press.html). (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…)

The Power of Graur to Explode ENCODE Using Incision and Derision

The consortium of investigators known as ENCODE (ENCyclopedia Of DNA Elements) published, with much publicity, a series of about thirty papers last fall purporting to “identify all functional elements in the human genome sequence” (https://www.genome.gov/ENCODE/).  Dan Graur, an evolutionary geneticist at the University of Houston, and his associates have published a paper in Genome Biology and Evolution (2013; online) challenging the assertion by the ENCODE investigators that 80.4% of the human genome can be considered functional (Nature, 2012).  Graur’s critique of the ENCODE claim is grounded in evolutionary principles. (more…)

Possible Degeneracy in Genotype-Phenotype Relationships due to DNA-RNA Sequence Disparity

An assumption fundamental to medical genetics is that the DNA sequence of an allele at a particular locus will (in the vast majority of instances) be faithfully transcribed into RNA and translated into protein.  This assumption has been largely accepted in spite of known rates of transcriptional and translational errors as well as special cases of RNA editing, in which enzymes alter the RNA sequence post-transcriptionally in ways that can influence translation.  If DNA-RNA-peptide sequence fidelity were reduced to zero, it would not be worth attempting to correlate genotype and phenotype.  More fundamentally, traits would not be heritable, thereby abrogating a necessary condition for Darwinian evolution.

 Therefore, the recent study by Li et al., in Science (2011) is of substantial interest.  The authors document numerous differences (still a minority) between DNA sequences and the putatively corresponding RNA sequences (referred to by the authors as RNA-DNA differenes or RDDs). (more…)