Posts in category Evolutionary biology

Nietzsche Undone: An Infection that Doesn’t Kill You Can Make You Weaker

The German philosopher, Friedrich Nietzsche, is known for a number of ideas among which a particularly oft-quoted one is, “That which does not kill us makes us stronger” ( A recent report in Cell (Fonseca et al., 2015) offers evidence that in the context of infection and immunity, the above aphorism may not be a reliable guide to reality. READ MORE »

Microbial Warfare and the Ecological Dynamics of Cystic Fibrosis Lung Disease

In a previous EMR post from December 30 of 2014 (see link below), I discussed a study (Science, 2014) that offered evidence for reciprocal selection of host and pathogen iron-binding proteins arising out the competition for their shared ligand, which is critical to the metabolisms of both parties to the conflict. A recent paper (J. Bacteriol., 2015) by Filkins et al. demonstrates another sort of competition focused on the acquisition of iron that can affect human health. This conflict occurs between two species of bacterial pathogen associated with lung disease in cystic fibrosis (CF) patients. READ MORE »

Fighting HIV Evolution with an Evolved Therapeutic Agent: Phase I Dose Escalation Clinical Trial of a Potent Broadly Neutralizing Human Antibody

In previous commentaries (;;, I have discussed the critical role of extensive B-cell and immunoglobulin gene evolution in generating broadly neutralizing antibodies for HIV-1.  Of course, the unprecedented magnitude of antibody evolution necessary to achieve potent neutralization of a high percentage of HIV strains reflects the unprecedented evolutionary plasticity of HIV that originates in both high mutation and recombination rates for the HIV genome (Korber et al., 2001).  A new study by Caskey et al. (Nature, 2015) from the Nussenzweig Laboratory reports results for a first-in-human dose escalation phase I clinical trial of a human monoclonal antibody (mAb) specific for the HIV envelope (env) protein. READ MORE »

A Functional Classification of Genomic Elements Informed by the Principles of Evolution

In an EMR commentary ( from March two years ago, I discussed issues related to the functional classification of genomic DNA sequences that arose in the context of claims from the ENCODE (ENCyclopedia Of DNA Elements) consortium.  A particular focus of that piece was an article by Graur and colleagues (2013) that offered an often humorous but rather stinging critique of the definition of “function” applied by the ENCODE authors to genomic DNA sequences.  Graur and two of his associates have now published (2015) an interesting and valuable functional classification of genomic sequences that is critically informed by their understanding of evolution. READ MORE »

Chromosomal Catastrophe (Chromothripsis) Causing Curative Clonal Conquest

Last month, Murphy and colleagues (Cell, 2015) published a fascinating report about a patient with an immunodeficiency syndrome that underwent spontaneous resolution.  The mechanism for this remarkable outcome points to the importance of somatic cell selection and evolution in the origins, pathogenesis, and most dramatically in this case, elimination of disease. READ 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. READ 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 (  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. READ 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. READ 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. READ 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. READ 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 (, 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. READ MORE »

Evolution and the Ebola Epidemic

Over the past several weeks the health news has been dominated by the outbreak of infections by Ebola virus (EBOV) in several West African nations: Guinea, Sierra Leone, Liberia, and Nigeria.  A study (Gire et al., 2014) published online at the end of August and now in print by a large collaborative group based in the U.S., the U.K., or West Africa applied massively parallel sequencing of the genomes of clinical isolates of the Ebola virus primarily from Sierra Leone. The results bear on the origins of the outbreak and the transmission patterns of the responsible virus lineages and may inform future investigations pertaining to diagnostic tests, the development of vaccines, and the design of therapies based on small-molecule drugs or biologics. READ MORE »

Epistasis in Adaptive versus Stochastic Evolution of the Influenza A Virus Nucleoprotein Gene

Epistasis refers to the influence of one genomic mutation or variant on the phenotypic effects of another mutation or variant.  Based on available evidence and theory, this phenomenon has a major influence on evolutionary trajectories for organisms of all sorts.  The role of epistasis has been studied primarily in the context of adaptive evolutionary change.  In a recent paper (2014), Gong and Bloom attempt to determine the relative frequencies of epistatic interactions in adaptive versus stochastic evolution, i.e. evolution driven by selection as opposed to evolution resulting from random processes without a significant selective ‘pressure.’  Gong and Bloom perform this comparison by analyzing homologous nucleoprotein (NP) genes in human and swine influenza A viruses.  The authors argue that the human viruses are subject to substantially more intense selection than the swine viruses since domestic swine are much shorter lived and their viruses are not as likely to be subjected to immune memory responses. READ MORE »

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 ( READ MORE »

The Future of the “Selfish Gene” Metaphor

This past December, science writer David Dobbs published an essay (2013) in the online magazine Aeon ( 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. READ MORE »

Illumination of the Multiple Sources of Selection Affecting Protein Sequences

Biomedical scientists and biologists routinely consider how selection shapes the structure and function of proteins of interest.  Less commonly, I suspect, do we consider how selection for attributes other than protein structure and function can favor or disfavor nucleotide sequences that encode particular amino acid sequences.   A new study (Stergachis et al., 2013) published in the December 13 issue of Science presents strong evidence for one particular source of selection (unrelated to protein function) influencing coding regions, known as exons, of genes.  This form of selection arises from the  fact, as revealed by the authors, that many transcription factors (TF), proteins that bind to specific nucleotide  sequences and regulate the frequency and pace of gene transcription (i.e., gene expression), bind in exonic regions of genes. READ MORE »

Human Phenotypic Differences and the Blurring Boundary Between Genetic and Epigenetic Variation

Three new papers (Kilpinen et al., 2013; McVickers et al., 2013; Kasowski et al., 2013) published earlier this month in Science all address the effects on human patterns of gene expression and other phenotypes of 1) genetic variation in non-protein coding regions of the genome and 2) covalent modifications of chromatin, the complex of DNA and proteins that facilitates the packaging and organization of DNA in the limited volume of the cell nucleus.  Regulation of gene expression is known to involve enzymes that covalently modify the chromatin proteins, known as histones, by attaching such moieties as methyl, acetyl, or phosphate groups to the so-called histone tails.  These post-translational modifications are commonly known as epigenetic marks and different marks, distinguished by both the chemical structure of the added substituent and the particular histone and precise amino acid modified, are associated with consistent and distinct effects on gene expression. READ MORE »

The Making of Metazoans: Cooperative Genes that Constrain Cheater Cells

In his 1987 book, “The Evolution of Individuality,” Leo Buss addressed a fundamental biological question: “How could individual multicellular animals (known as metazoans), like sea anemones, insects, frogs, and humans arise?”  Buss focused on a key challenge confronting any multicellular animal with differentiated cell types performing different functions: the potential conflict between selection on the whole organism and selection on the cells that constitute the organism (or on the whole genome and the individual genes that constitute the genome).   A new study (Dejosez et al., Sciencexpress, 2013) explores this issue by using a genome-wide screen to identify genes that favor cell cooperation and discourage so-called “cheater” cells that through genetic or epigenetic variation outcompete wild-type cells in the developing embryo. READ MORE »

Boundary-Breaking Evolution via B Lymphocyte Clonal Selection in Response to HIV-1

A central focus of recent research aimed at developing a vaccine for HIV-1 is the identification of potent broadly-neutralizing antibodies (bNAbs).  Due to work from several laboratories, many such antibodies have now been identified, produced in quantity as monoclonal antibodies, and characterized with respect to key properties such as epitope specificity, affinity for the corresponding HIV-1 epitope, and neutralizing activity against many strains of varying susceptibility to antibody-mediated inactivation (important examples of these publications are: Scheid et al., 2009; Walker et al., 2009; Wu et al., 2010; Walker et al., 2011; Huang et al., 2012).  These successes notwithstanding, the scale of the challenge facing the vaccine developers is clarified by the following facts: 1) potent bNAbs only develop in 10-30% of infected individuals, 2) it typically takes between two and three or four years after initial infection for these antibodies to appear in the blood of these individuals, and 3) antibodies with the desired attributes often have extraordinary numbers of somatic mutations in the variable domains that mediate binding to the HIV-1 antigen (Klein et al., 2013a).   A study (Klein et al., 2013b) published earlier this year from the laboratory of Michel Nussenzweig both illuminates one possible factor accounting for the impressive length of time and number of mutations associated with the generation of potent bNAbs and provides an extraordinary example of the power of intense selection to confound expectations arising from previously observed associations.  In this instance, the undermined expectations related to the well-established functional correlates of hypervariable and framework regions within antibody variable domains. READ MORE »

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