The Evolution & Medicine Review

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, a neuropathy) when many candidate genes had already been identified by other methods.

A  review in Nature (Witkowski, 2010), of a new book reprising the history of the initial sequencing of the human genome, notes that key antecedents to the genome project included such developments as restriction enzymes, analysis of restriction fragment length polymorphisms, and polymerase chain reaction.  What has not been much remarked upon is how the current range of genomic applications to both basic research (including those related to evolutionary medicine) and clinical medicine can be traced back to some lines of inquiry that were primarily initiated by the desire to find answers to abstract questions or clarify abstruse concepts, i.e. research directions motivated by curiosity.  These questions or concepts were not originally regarded as having much whatever to do with such practical concerns as reducing the suffering associated with human diseases.  Three individuals and their intellectual quests are especially pertinent and illustrative. Continue Reading »

Tags: Alan Turing, complementarity, computation, curiosity, genotyping, human disease, human evolution, James D. Watson, Max Delbrück, molecular nature of the gene, Salvador Luria, universal Turing machine, whole-genome sequence determination

Science 12 August, 2010:   An allele that increases the risk of hypertension induced renal failure 10 fold,  lyses Trypanosoma brucei rhodesiense and is more common in populations with exposure to sleeping sickness.

Summary from This Week in Science

Kidney disease is more common in African Americans than in Americans of European descent, and genetics is likely to be a major contributing factor. Genovese et al. (p. 841, published online 15 July) now show that African Americans who carry specific sequence variants in a gene on chromosome 22 encoding apolipoprotein L-1 (APOL1) have an increased risk of developing hypertension-attributed end-stage kidney disease or focal segmental glomerulosclerosis. These variants are absent from European chromosomes. Among the functions ascribed to APOL1 is the ability to lyse and kill trypanosomes. Intriguingly, APOL1 derived from the risk alleles, but not the “wild-type” allele, killed Trypanosoma brucei rhodesiense, which causes African sleeping sickness.

Science 13 August 2010:  Vol. 329. no. 5993, pp. 841 – 845    DOI: 10.1126/science.1193032

Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans

Giulio Genovese,^1,2,* David J. Friedman,^1,3,* Michael D. Ross,⁴ Laurence Lecordier,⁵ Pierrick Uzureau,⁵ Barry I. Freedman,⁶ Donald W. Bowden,^7,8 Carl D. Langefeld,^8,9 Taras K. Oleksyk,¹⁰ Andrea L. Uscinski Knob,⁴ Andrea J. Bernhardy,¹ Pamela J. Hicks,^7,8 George W. Nelson,¹¹ Benoit Vanhollebeke,⁵ Cheryl A. Winkler,¹² Jeffrey B. Kopp,¹¹ Etienne Pays,^5, Martin R. Pollak^1,13,

African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease–associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.

Concepts of evolutionary medicine and energy regulation contribute to the etiology of systemic chronic inflammatory diseases.

By Straub RH.  Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Division of Rheumatology, Department of Internal Medicine I, University Hospital Regensburg, Germany.

Brain Behav Immun. 2010 Aug 9. [Epub ahead of print] (not open access)
Abstract
The etiology of chronic inflammatory diseases (CIDs) is usually based on four criteria: Continue Reading »

Darwinian medicine: Does intensive care kill or cure?

New Scientist, 11 August 2010 by Dan Jones

We’ve evolved ways to come back from the brink of death – and doctors’ efforts to help may just be getting in the way

NOTHING epitomises cutting-edge medicine so much as a modern intensive care unit. Among the serried ranks of shiny chrome and plastic surrounding each bed are machines to ventilate the lungs and keep failing kidneys functioning, devices to deliver drugs intravenously and supply sedatives, tubes to get food into a patient and waste out, and countless gizmos to monitor blood composition, heart rate, pulse and other physiological indicators.

This environment is home to Mervyn Singer, director of the Bloomsbury Institute Centre for Intensive Care Medicine at University College London. So you might expect him to wax lyrical about the wonders of medical technology. Instead, he has this to say: “Virtually all the advances in intensive care in the past 10 years have involved doing less to the patient.” And he goes further, arguing provocatively that modern critical care interferes with the body’s natural protective mechanisms- that patients often survive in spite of medical interventions rather than because of them.  Read more

Two recent papers published online at scienceexpress.org describe studies of antibodies claimed to interfere with infection of host cells by a wide range of HIV-1 strains.  These studies strongly suggest that the evolutionary potential of the humoral immune response may be necessary to combat the diversity of HIV-1 antigens that results from the extraordinary pace of HIV-1 evolution. Continue Reading »

Tags: affinity maturation, antibody evolution, CD4-binding site, gp120, HIV-1, somatic hypermutation, virus neutralization

Disease as a byproduct of adaptation

An article chock full of content on antagonistic pleiotropy and balancing selection  by Razib Khan on the  Discover Magazine web page.

The deep reach of the pharmaceutical industry into academic and clinical medicine sets up ample opportunity for conflicts of interest on the part of biomedical researchers. To minimize the risks that such conflicts could introduce bias into the scientific literature, most publications impose reporting regulations that make transparent any financial stake that an individual researcher may have in the subject of his or her publications. Similarly, most institutions regulate the nature and scope of such financial agreements.

However, there appears to be significantly less oversight when it comes to an individual researcher’s ability sign away freedom of inquiry and publication. In a commentary in this week’s Chronicle of Higher Education, Harvard School of Public Health professor Marc Lipsitch points out that few universities have explicit regulations to prohibit researchers from signing consultation agreements that severely curtail their freedom to express their opinions or choose the direction of their research. And in the absence of such regulations, Big Pharma are starting to ask for precisely these types of contractual restrictions. Lipsitch reports his own experience: Continue Reading »

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®). Continue Reading »

Tags: drug resistance, evolvability, fitness, influenza neuraminidase, mutation, oseltamivir, phylogenetics, protein folding, protein stability, viral evolution

I recently completed reading one of the most stimulating books (1) on the conceptual aspects of evolution that I have read in many years.  The author, Peter Godfrey-Smith is a philosopher of biology at Harvard.  He has written widely on topics in the philosophy of science and is the author previously of an exceptionally thoughtful introduction (2) to that field.

The new book is intended both to clarify philosophical thinking about concepts central to evolutionary theory and to advance biological understanding of the processes of evolution.  Godfrey-Smith also proposes as an objective of the book, if I can do his precise wording justice in abbreviated form, the implications of evolutionary science for broader questions of interest to philosophers, scientists, and perhaps others. Continue Reading »

Tags: agential perspective on evolution, cultural evolution, levels of selection, minimal requirements for natural selection, population attributes, population thinking, reproduction, “gene’s eye view” of evolution

Soscia, et al.   in  PLoS One. 2010; 5(3): e9505 (open access)          doi: 10.1371/journal.pone.0009505.

The Alzheimer’s Disease-Associated Amyloid  beta Protein Is an Antimicrobial Peptide

Evolutionary epidemiology 20 years on: Challenges and prospects

A couple of months ago, my institution hosted a one-day symposium on phylogenetics. One of the speakers was John Avise, a member of the National Academy of Sciences and the individual generally credited with originating the field of phylogeography. His talk and those of two other speakers were focused on subjects most typically regarded as part of biology, not medicine. However, the fourth lecturer on the program applied some of the same methods and patterns of thought to the interactions between HIV and its human hosts, thereby illustrating the potential relevance of phylogenetic analysis to matters of clinical significance. A recent paper in Science (Harris et al., 2010) provides another such example.

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of major significance in many countries. According to Maryn McKenna (2010), author of a recent book on this pathogen, there are almost 19,000 deaths and almost 370,000 hospitalizations annually attributable to MRSA infections in the United States. The yearly total costs for these infections are estimated to be in the billions of dollars. Continue Reading »

Tags: accessory genome, antibiotic resistance, convergent evolution, core genome, genotyping, indels, mobile genetic elements, mutation rate, next-generation DNA sequencing, SNPs, virulence

Physicians who care for patients with malaria or who study malaria pathogenesis have been most concerned with merozoites, the asexual form of the parasite that infects red blood cells and that is responsible for the pathological manifestations of the disease. From evolutionary and public health perspectives, however, we need to pay more attention to gametocytes, the sexual forms that are transmitted to mosquitoes. Malaria parasites have evolved life history strategies that maximize their transmission to mosquitoes and then on to new hosts, and this has presumably involved optimizing the production and transmissibility of gametocytes over the course of an infection. Continue Reading »

The complete course on evolutionary biology taught by Stephan Stearns at Yale is now available on the web.  It free, wonderful, and accessible from anywhere.

POSTDOCTORAL FELLOWSHIPS IN EVOLUTIONARY BIOLOGY AND RELATED FIELDS Continue Reading »

The Final Report from the Symposium on Evolution and Diseases of Modern Civilization at the Berlin Charité provides an overview and reports from all five workshops in a single pdf.

For a copy, click here.

Medicine, evolution and natural selection: An historical overview

By Fabio Zampieri

Quarterly Review of Biology 84 (4) 2009, p 333-355.

Investigation of model organisms can sometimes be misleading about the biology of humans, but this is often because expectations about similarities between different species, especially when studied in substantially different contexts, are unrealistic (Casanova and Abel, 2004). Viewed as entities of roughly comparable complexity, model organisms can be of value more as approximate guides to what complexities and intricacies might be encountered than as templates permitting precise one-to-one extrapolations among comparable genes, gene products, or networks of interactions.

It is in the spirit endorsed in the preceding paragraph that a paper (2009) by Ralph Greenspan (no known familial connection) on the genetics of behavior in Drosophila is of particular interest. Greenspan reviews studies of selection (of fruit flies) for several different behavioral phenotypes (e.g., aggression, mating speed, and locomotor activity), in which gene expression changes in fly heads (i.e., primarily brain tissue) are assessed. Continue Reading »

Tags: gene expression profiling, gene networks, large-effect mutants

POST-CONFERENCE UPDATE, 24th March 2010

• A report on the conference is here (pdf); thanks to Gillian Pepper
• Photos from the conference are here; thanks to Nick Pound
• The programme with abstracts is here (pdf)
• The list of registered attendees is here (pdf)