In 1996, Dean et al. (Science), demonstrated that a loss-of-function allele (CCR5Δ32) encoding a version of the chemokine receptor, CCR5, confers very substantial resistance to infection with HIV-1 in the homozygous state and slows progression in the heterozygous state. Given the relatively recent origin of HIV-1, this finding raised the question of what source of selection could account for the frequency, approximately 0.08 among Caucasians according to Dean et al., of this allele. A recent paper (Alonzo et al., 2013) offers new information on a relationship between CCR5 and a different pathogen that might offer insight into the evolutionary trajectory of CCR5Δ32.
The new study presents compelling evidence that leukotoxin ED (LukED), one of a family of bi-component exotoxins produced by Staphylococcus aureus, can bind to CCR5 and thereby cause cell death. LukED consistently produces substantially more cytotoxicity for CCR5+ than CCR5– cell lines of several types. Ligands for CCR5, including the drug, maraviroc, which is approved for clinical treatment of HIV-1 infection, significantly inhibit both the binding of LukED to cells and the magnitude of associated cytotoxicity. LukED also binds to and kills CCR5+ primarycells, such as human memory T cells, macrophages, and dendritic cells. READ MORE »
In the book, The Winner-Take-All Society (1995), Robet H. Frank and Philip J. Cook discuss a hypothetical scenario in which a new genetic technique allows babies to be engineered so that they have a 99% chance of performing 15% better on the standardized tests used in American college admissions, such as the Scholastic Aptitude Test (SAT) without actually being smarter in other contexts. In 1% of babies so engineered, a severe emotional disability will result. Frank and Cook speculate that many parents would be willing to risk the odds that an enginnered child would not be among the 1% of offspring who suffer the ontogenetic costs of the procedure. They further argue that as more people exploit this genetic modification, the emotional pressure on the hold-outs would increase. READ MORE »
Since the announcement, approximately ten years ago in June of 2000, that a first draft of the (almost) complete nucleotide sequence of a human genome had been assembled, much interest has been directed to the ways in which genomic information can facilitate investigation into the evolutionary origins of humans and their diseases as well as to the ways in which this new knowledge can be put to practical use in medicine and other fields of endeavor. For example, just a few months ago, James Lupski and colleagues published an article (2010) in The New England Journal of Medicine that illustrated the potential of whole-genome sequence determination of a proband and more focused genotyping of family members to identify the genotype responsible for a disease phenotype (for the curious, Charcot-Marie-Tooth disease, READ MORE »