Intelligent Design, the Resurfacing of a Pseudo-Theory

In the past six months, I have encountered a review, by Thomas Nagel in The New York Review of Books (2012), of Alvin Plantinga’s latest book (Where the Conflict Really Lies: Science, Religion, and Naturalism, 2011 ) and a review, by Alvin Plantinga in The New Republic (2012), of Thomas Nagel’s latest book (Mind and Cosmos: Why the Materialist Neo-Darwinian Conception of Nature is Almost Certainly False, 2012).  Both authors are regarded as distinguished philosophers.  In their respective books, they both criticize what may be called the materialist neo-Darwinian approach to explaining life.  Plantinga and Nagel both discuss as a putative alternative to evolutionary explanations, the framework known as intelligent design (ID).  Whereas Plantinga appears to support ID, Nagel does not endorse ID but criticizes proponents of evolution for being overly disparaging of ID theorists. (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…)

Man, Machine, and Metaphorical Misdirection

The imitation of living and sentient beings by machines is recently much on the minds of many Americans.  A computer designed and built by scientists and engineers at IBM, “Watson,” convincingly defeated two former “Jeopardy” champions in a televised competition on the long-running game show.  This triumph of a machine over humans has stimulated both recollections of the last hallmark event in this series, the defeat (in six games in May of 1997) of chess grand master Garry Kasparov by another IBM computer, “Deep Blue,” and speculation about the future of artificial intelligence.  

Interest in the ability of computers to simulate human thought and intelligence persists in parallel with the tendency of many biologists and biomedical scientists to think of biochemical entities, (such as transcription, splicing, and signaling complexes), cells, and whole organisms as analogous to machines.  For example, the hijacking of cellular processes by viruses often invokes a phrase referring to the exploitation, by the virus, of cellular “machinery.”  Biologists frequently refer to cellular structures, like ribosomes, as “molecular machines.”  (more…)

The Prominence and Pertinence of Pleiotropy

Randy Nesse recently reviewed a new book (“The Evolution of Obesity” by Power and Schulkin) on weight regulation [Nature, 2009)].  In the course of the review, Nesse took note of the authors’ evidence that leptin-associated function is highly context-dependent, where context includes tissue, age, general organismal condition, and the concentrations of other molecules that regulate metabolism.  Consequently, Nesse concluded that, “Attributing one function to a hormone is attractive, but often wrong.”   

Based on the preceding, it would be reasonable to expect that the gene encoding leptin would exhibit pleiotropy, the property by which mutations of a single gene can influence multiple traits or phenotypes.  Evidence supporting this inference has been obtained in mice, where homozygosity for a nonsense mutation that shortens the leptin gene product and causes deficient signaling through the leptin receptor is associated with phenotypes including increased body weight, decreased fat-free body mass, decreased lung and mammary tumor incidence, increased blood concentrations of insulin and cortisol, and decreased fertility relative to control, leptin-replete mice (Wolff, GL. J Nutr. 1997). 

An experience that brought to mind Nesse’s point about hormones frequently having multiple functions was my recent reading of Michael Sandel’s book, “The Case Against Perfection: Ethics in the Age of Genetic Engineering.” (more…)

Growing Complexities in Relating Genotype to Phenotype

Geneticists and evolutionary biologists have for decades embraced the view, no doubt reinforced by terminology such as “silent” (i.e., synonymous) mutations, that for protein-encoding genes, genotype determines phenotype through control of the amino acid sequence of the corresponding polypeptide chain or chains.  In various contexts, the standard assumption has therefore been that only non-synonymous nucleotide substitutions in a gene have an impact on the phenotype and are subject to selection.

In 2007, Kimchy-Sarfaty et al. (Science) described a likely exception to the conventional wisdom (more…)