Autism, the Evolution of Homo sapiens sapiens, and the Definition of “Human”

Autism, the Evolution of Homo sapiens sapiens, and the Definition of “Human”

There is reason to believe that among the key traits that distinguish humans from the primates that are phylogenetically closest to us are cognitive and social abilities as exemplified by language and diverse aspects of social interaction and cultural expression. It is reasonable to speculate that these characteristic human phenotypes are based on differences from closely related species in neural development, which in turn ought to reflect differences in the nucleotide sequences of the genes that encode proteins or RNA molecules involved in this process. A study (1) published in Cell in October of this year by Christopher A. Walsh of Harvard Medical School, his associates, and collaborators from numerous institutions focuses on so-called human accelerated regions (HARs), portions of the human genome that have diverged more rapidly than other regions from the genomes of the species most closely related to humans. Doan et al. sought to identify mutations in HARs that are associated with abnormal cognition and social behavior of the sort that can be found in autism. (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 ( (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. (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. (more…)

The Challenge of Breaking the Meta-Code: Context and the Meaning of the Genome

In lay publications, it is commonplace for writers to refer to the deoxynucleotide sequence of an individual’s nuclear genome as that individual’s “code” and to the determination of that sequence as “deciphering the code.”   Molecular biologists mean by the “genetic code,” not a DNA sequence but the relationships between RNA (or DNA) nucleotide triplets and particular amino acids.  For those interested in clinical genetics, the real code-deciphering challenge is much more daunting than determining nucleotide sequences; it is the mapping of genotypes to medically-relevant phenotypes, i.e. predicting diseases from the totality of sequences in a genome.

The somewhat cryptic paradox at the heart of genome-based personalized medicine at the present state of our understanding is easily put: (more…)