Amino Acid Gymnastics and the Evolution of Influenza Virus Resistance to Oseltamivir

In previous posts, I discussed, respectively, the use of selection to generate an antibody of potential value in treating influenza A virus infections (1) and the relevance of protein dynamics to the evolution of protein function (2).   A recent paper in Science (3) offers evidence suggesting that internal protein dynamics play a crucial role in shaping the evolution and spread of resistance to the influenza neuraminidase inhibitor, oseltamivir (Tamiflu®). (more…)

Do we expect the body to be a “One Hoss Shay”?

In an 1858 humorous poem The Deacon’s Masterpiece, or the Wondeful One Hoss Shay, Oliver Wendell Holmes Sr. described a carriage so artfully constructed as to have no weakest link. The carriage ran smoothly for exactly a hundred years, and then one day

it went to pieces all at once, –
All at once, and nothing first, –
Just as bubbles do when they burst,

leaving its driver sitting atop a pile of rubble and dust.

(more…)

Selection and the Context-Dependence of Phenotypic Optimization

I recently saw the movie, “The Blind Side,” based on a book of almost the same name (“The Blind Side: Evolution of a Game”) by author, Michael Lewis. The reference to “evolution” in the book title refers to the adaptations necessitated in the (American) game of football on the offensive line, especially at the left tackle position, by the appearance of a larger, faster, more aggressive brand of pass rusher (i.e., a defensive player who seeks to tackle the opposing quarterback), exemplified by Lawrence Taylor, formerly of the New York Giants.   Of particular concern are defensive players attacking the quarterback from the latter’s back, or “blind,” side as they prepare to throw a pass .  Consequently, large, quick, agile left tackles able to fend off such incursions became more valuable than was previously the case.

The non-fiction plot of “The Blind Side” revolves around an unusually large (6’5″ and >300 lbs.) and athletic young man, Michael Oher, who was from a less-advantaged part of Memphis and never had a stable family life.  He is taken in by a wealthy white family and is given the opportunity to play football for an elite private high school.   In his debut on the defensive line, where one key objective (perhaps counter-intuitively) is to aggressively pursue the opposition quarterback, he fails to impress, but when he is switched to the offensive line, where defending the quarterback on pass plays is a crucial function, he becomes an all-star performer.  Although Oher’s size, strength and speed could conceivably have been of exceptional value in either position, Michael Lewis suggests that his preference for protectiveness over uninhibited aggression made his overall profile much better suited to one role than the other.

An important point to consider when reflecting on the tendency of evolution by natural selection to enhance organismal fitness is that such improvement is not generally usefully regarded as approaching perfection.  A major reason for thinking of fitness in less than absolute terms is that environments can fluctuate in ways that critically influence survival and reproduction such that a phenotype that appears to be well-adapted to one set of circumstances (Michael Oher on the offensive line) may be much less advantageous in a different set of circumstances (Michael Oher on the defensive line).  A recent paper by Hensley et al. beautifully illustrates this point at a molecular level. (more…)

The appendix, appendicitis, and appendectomy

The human appendix has long fascinated both biologists and physicians. A recent bout of appendicitis has heightened my interest in this organ and has stimulated me to write about it. Because of its small and variable size, anThe human vermiform appendix (image from the Talk Origins Archive; www.talkorigins.org)d its apparent uselessness, Darwin (1871) believed that the appendix was a rudiment, or vestigial organ. The caecum is large in many herbivores, in whom it is thought to play a role in the digestion of high-fiber foods. It presumably grew smaller during the course of primate evolution, leaving the appendix as a vestige. Like the rest of the colon, the appendix is rich in lymphatic tissue and its epithelial surface is coated with a biofilm. These properties have led to suggestions that the appendix has been preserved by natural selection because of its immunological functions or because it is a reservoir for commensal bacteria (Bollinger et al. 2007). It seems more likely, however, that these properties simply reflect the development of the appendix as part of the colon; there is little reason to believe that the appendix has unique or especially important immunological or microbiological functions. People who have their appendices removed or who are born with congenital absence of the appendix don’t exhibit any physiological deficits. Darwin was almost certainly correct—the appendix is a rudiment. (more…)