Geneticists have recognized for some time that many genes exhibit pleiotropy, meaning that one mutation can manifest in two or more distinguishable phenotypic effects. In a fascinating study recently published in Science [2014 Jan 10;343(6167):152-7. doi:10.1126/science.1246886], Joseph et al. offer evidence for an example of pleiotropy in which the distinct phenotypic effects associated with mutation of the POLR3A gene, which encodes a subunit (RPC1) of RNA polymerase III, are associated with two different diseases: one or another form of cancer and an autoimmune disease (scleroderma). Continue Reading »
Greaves, Mel. (2014).Was skin cancer a selective force for black pigmentation in early hominin evolution? Proceedings of the Royal Society B: Biological Sciences, 281(1781). doi: 10.1098/rspb.2013.2955 (open access)
Melanin provides a crucial filter for solar UV radiation and its genetically determined variation influences both skin pigmentation and risk of cancer. Genetic evidence suggests that the acquisition of a highly stable melanocortin 1 receptor allele promoting black pigmentation arose around the time of savannah colonization by hominins at some 1–2 Ma. The adaptive significance of dark skin is generally believed to be protection from UV damage but the pathologies that might have had a deleterious impact on survival and/or reproductive fitness, though much debated, are uncertain. Here, I suggest that data on age-associated cancer incidence and lethality in albinos living at low latitudes in both Africa and Central America support the contention that skin cancer could have provided a potent selective force for the emergence of black skin in early hominins.
The Center and the School of Life Sciences invite applications for two open rank faculty positions for Cancer researchers with a preference for one associate/full and one assistant professor. Continue Reading »
Background and objectives: Conventional antibiotics select strongly for resistance and are consequently losing efficacy worldwide. Extracellular quenching of shared virulence factors could represent a more promising strategy because (a) it reduces the available routes to resistance (since extracellular action precludes any mutations blocking a drug’s entry into cells or hastening its exit) and (b) it weakens selection for resistance, since fitness benefits to emergent mutants are diluted across all cells in a cooperative collective. Here, we tested this hypothesis empirically.
Methodology: We used gallium to quench the iron-scavenging siderophores secreted and shared among pathogenic Pseudomonas aeruginosa bacteria, and quantitatively monitored its effects on growth in vitro. We assayed virulence in acute infections of caterpillar hosts (Galleria mellonella), and tracked resistance emergence over time using experimental evolution.
Results: Gallium strongly inhibited bacterial growth in vitro, primarily via its siderophore quenching activity. Moreover, bacterial siderophore production peaked at intermediate gallium concentrations, indicating additional metabolic costs in this range. In vivo, gallium attenuated virulence and growth – even more so than in infections with siderophore-deficient strains. Crucially, while resistance soon evolved against conventional antibiotic treatments, gallium treatments retained their efficacy over time.
Conclusions: Extracellular quenching of bacterial public goods could offer an effective and evolutionarily robust control strategy.
A careful reading of the review of fever in “Fever: Friend or Foe?”, reveals the embarrassing deficiency in medical science’s understanding of how fever, much less anorexia, functions in infection. Since fever (as well as anorexia and other components of the acute-phase response) is induced by our own cytokines, it is virtually axiomatic that fever has been more beneficial than harmful on an evolutionary scale (since otherwise the response would have been deleted). As a “fan” of fever, I’ve compiled a list of six potential benefits of fever, each of which is found in the literature and has a reasonable experimental or theoretical basis (and each likely has some degree of correctness). Note that the first four are based on fever being a heat stressor. Have a look and then see my take on it.
Fever may work by:
1) directly harming pathogens,*
2) inducing apoptosis of infected cells (and neoplastic cells),
3) inducing host’s heat shock proteins to protect host cells during infection,
4) inducing heat shock proteins in pathogens—extracellular heat shock proteins activate immune responses as “danger signals”,
5) increasing efficacy of immune responses since they work better at slightly elevated temperatures,*
6) turning down the immune response by causing apoptosis of neutrophils and lymphocytes. Continue Reading »
Last month, I completed teaching a graduate course for the tenth time. After several years (in the early 1990’s) of thinking about launching a new alternate-year seminar course and then planning it, I began teaching PATH 480 in the fall of 1994. The original name of the course, maintained through the first seven times I taught it, was: “Immunology, Evolution and Logic.” Beginning in 2009, another faculty member, Derek Abbott, joined me in teaching the course, and the title was revised to: “Logical Dissection of Biomedical Investigations.” In my portion of the course, I retained an emphasis on the relevance of logic and evolutionary principles to thinking about immune recognition and immune functioning more generally. I focused class sessions on concepts and underlying assumptions critical to experimental investigations as well as on experimental design and data interpretation in articles reporting studies pertaining to immune recognition. Dr. Abbott has focused his portion of the course on the practical cognitive skills involved in reviewing papers and grant proposals pertaining primarily to innate immune signaling. Continue Reading »
The Evolution, Medicine, & Public Health Foundation invites nominations for the Omenn Prize of $5000 to be awarded in April 2014 for the best article published in 2013 in any scientific journal on a topic related to evolution in the context of medicine and public health.
The prize, provided by the generosity of Gilbert S Omenn, will be awarded to the first author of the winning article. Nominations, including a brief statement in the body of the email (max. 250 words), a copy of the article (if distribution is permitted) or abstract and article link, must be submitted by 5pm, 28 February, 2014 US Eastern Standard Time to OmennPrize@evolutionarymedicine.org . Authors are encouraged to nominate their own articles, but nominations of articles by others are also welcome.
Any relevant peer-reviewed article is eligible, but the prize is intended for work that uses evolutionary principles to advance understanding of a disease or disease process. The prize committee will give priority to articles with implications for human health, but many basic science or theoretical articles have such implications.
The Prize Committee is chaired by Allen Rodrigo, and its members are Carl Bergstrom and Sarah Tishkoff. Papers by committee members, their students and lab group members are not eligible, and articles by their co-authors or close associates are subject to special conditions.
Background and objectives: Interbirth intervals (IBIs) mediate a trade-off between child number and child survival. Life history theory predicts that the evolutionarily optimal IBI differs for different individuals whose fitness is affected by how closely a mother spaces her children. The objective of the paper is to clarify these conflicts and explore their implications for public health.
Methodology: Simple models of inclusive fitness and kin conflict address the evolution of human birth-spacing.
Results: Genes of infants generally favor longer intervals than genes of mothers, and infant genes of paternal origin generally favor longer IBIs than genes of maternal origin.
Conclusions and implications: The colonization of maternal bodies by offspring cells (fetal microchimerism) raises the possibility that cells of older offspring could extend IBIs by interfering with the implantation of subsequent embryos.
The ASU Center for Evolution, Medicine & Public Health (CEMPH) will host several events to celebrate the center’s launch. Directed by Randolph Nesse, a founder of the field of evolutionary medicine, the center’s mission is to establish evolutionary biology as a basic science for medicine and public health worldwide. Research is at its core, but the center will also have major commitments to education, outreach and developing similar programs elsewhere. The new center synergizes with the ASU Center for Evolutionary Medicine and Bioinformatics, directed by Sudhir Kumar, by augmenting existing strengths in phylogenetics, with new faculty whose research uses basic evolutionary principles to understand problems such as antibiotic resistance, cancer, autoimmune disease, aging and behavioral disorders.
SCHEDULE OF EVENTS – open to the public
Fri., January 17, 2-3:15 p.m. in LSE 104 (refreshments served beforehand)
William Aird, Professor of Medicine, Harvard Medical School, Director, Center for Vascular Biology Research Beth Israel Deaconess Medical Center
Galen, hagfish and the bench-to-bedside gap in endothelial biomedicine: a noisy affair
Tues., January 21, 1-6:30 p.m. in Memorial Union 241
Symposium on Evolution, Medicine & Public Health: The Great Opportunity
1 p.m. Mark Flinn, Professor & Chair of Anthropology, University of Missouri Hormones in the wild: Physiological adaptations for human social relationships
2:30 p.m. Andrew Read, Alumni Professor in the Biological Sciences, Professor of Entomology, and Director, Center for Infectious Disease Dynamics The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy
4 p.m. Panel discussion with the four visitors and ASU faculty, led by Randolph Nesse Making evolutionary biology a basic science for medicine worldwide: What can ASU do?
5:30 p.m. Open reception for all who share an interest in evolution and medicine
Weds., January 22, noon-1 p.m. ISTB-1 401
Bernard Crespi, Professor of Biology, Simon Fraser University Where Darwin meets Freud: Evolutionary biology and the genetics of autism, psychosis, and the social brain
To join the listserv for CEMPH events send a note to CEMPH@asu.edu
For a printable color poster for the events, click here.
For a folder with the speaker’s CV’s and papers, click here.
Biomedical scientists and biologists routinely consider how selection shapes the structure and function of proteins of interest. Less commonly, I suspect, do we consider how selection for attributes other than protein structure and function can favor or disfavor nucleotide sequences that encode particular amino acid sequences. A new study (Stergachis et al., 2013) published in the December 13 issue of Science presents strong evidence for one particular source of selection (unrelated to protein function) influencing coding regions, known as exons, of genes. This form of selection arises from the fact, as revealed by the authors, that many transcription factors (TF), proteins that bind to specific nucleotide sequences and regulate the frequency and pace of gene transcription (i.e., gene expression), bind in exonic regions of genes. Continue Reading »
Book Review The story of the Human Body: Evolution, Health & Disease By Daniel Lieberman
Publishers: Pantheon Books, Random House, USA (2013) and Allen Lane (UK) 2013 ISBN: 978-1-846-14393-9 (Amazon link here)
Review by Sir Peter Gluckman, Centre for Human Evolution, Adaptation and Disease, Liggins Institute University of Auckland
In recent years there have been a growing number of popular books that try and put an evolutionary perspective on the human condition. In general they have suffered from either over-claiming the relevance of the particular perspective they have taken, or from over simplifying complex contexts in which their particular disease focus is set. I must admit to having co-authored a couple that suffer from these criticisms. The challenge with such books is always for whom is the author writing. Is it to educate and inform the general public, to educate health care professionals, (too many of whom are sadly lacking in knowledge in evolutionary medicine) or is it to incite some particular actions in society, medicine or public health. In a sense all three tend to be part of an author’s agenda and this tends to put both a challenge on both the author and the reader. Continue Reading »
By Monahan-Earley, R., Dvorak, A. M., & Aird, W. C. (2013). In Journal of Thrombosis and Haemostasis, 11, 46-66. doi: 10.1111/jth.12253 (open access)
Summary: Every biological trait requires both a proximate and evolutionary explanation. The field of vascular biology is focused primarily on proximate mechanisms in health and disease. Comparatively little attention has been given to the evolutionary basis of the cardiovascular system. Here, we employ a comparative approach to review the phylogenetic history of the blood vascular system and endothelium. In addition to drawing on the published literature, we provide primary ultrastructural data related to the lobster, earthworm, amphioxus, and hagfish. Existing evidence suggests that the blood vascular system first appeared in an ancestor of the triploblasts over 600 million years ago, as a means to overcome the time-distance constraints of diffusion. The endothelium evolved in an ancestral vertebrate some 540–510 million years ago to optimize flow dynamics and barrier function, and/or to localize immune and coagulation functions. Finally, we emphasize that endothelial heterogeneity evolved as a core feature of the endothelium from the outset, reflecting its role in meeting the diverse needs of body tissues.
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. Continue Reading »
Abstract: Somatic evolution during cancer progression and therapy results in tumour cells that show a wide range of phenotypes, which include rapid proliferation and quiescence. Evolutionary life history theory may help us to understand the diversity of these phenotypes. Fast life history organisms reproduce rapidly, whereas those with slow life histories show less fecundity and invest more resources in survival. Life history theory also provides an evolutionary framework for phenotypic plasticity, which has potential implications for understanding ‘cancer stem cells’. Life history theory suggests that different therapy dosing schedules might select for fast or slow life history cell phenotypes, with important clinical consequences. Link to Nature Reviews Cancer Site
By Vittecoq M, Roche B, Daoust SP, Ducasse H, MissÈ D, Abadie J, et al.
in Trends in ecology & evolution 2013;28(11):628-35. Open access
SummaryCancer is a disease that affects the majority of metazoan species and, before directly causing host death, is likely to influence the competitive abilities of individuals, their susceptibility to pathogens, their vulnerability to predators, and their ability to disperse. Despite the potential importance of these ecological impacts, cancer is rarely incorporated into model ecosystems. We describe here the diversity of ways in which oncogenic phenomena, from precancerous lesions to generalized metastatic cancers, may affect ecological processes that govern biotic interactions. We argue that oncogenic phenomena, despite their complexity, can have significant and sometimes predictable ecological consequences. Our aim is to provide a new perspective on the ecological and evolutionary significance of cancer in wildlife, and to stimulate research on this topic.
Abstract: In the last few decades, pediatric medicine has observed a dramatic increase in the prevalence of hitherto rare illnesses, among which obesity, diabetes, allergies and other autoimmune diseases stand out. In addition, secular trends towards earlier onset of puberty and sexual activity contribute to the psychological problems of youth and adolescents. All this has occurred in spite of the improved health care provision for children, yet traditional concepts of medicine have failed to explain these new epidemics? Continue Reading »
Association mapping can be viewed as an application of population genetics and evolutionary biology to the problem of identifying genes causally connected to phenotypes. However, some population-genetic principles important to the design and analysis of association studies have not been widely understood, or have even been generally misunderstood. Some of these principles underlie techniques that can aid in the discovery of genetic variants that influence phenotypes (“windfalls”), whereas others can interfere with study design or interpretation of results (“pitfalls”). Continue Reading »
In his 1987 book, “The Evolution of Individuality,” Leo Buss addressed a fundamental biological question: “How could individual multicellular animals (known as metazoans), like sea anemones, insects, frogs, and humans arise?” Buss focused on a key challenge confronting any multicellular animal with differentiated cell types performing different functions: the potential conflict between selection on the whole organism and selection on the cells that constitute the organism (or on the whole genome and the individual genes that constitute the genome). A new study (Dejosez et al., Sciencexpress, 2013) explores this issue by using a genome-wide screen to identify genes that favor cell cooperation and discourage so-called “cheater” cells that through genetic or epigenetic variation outcompete wild-type cells in the developing embryo. Continue Reading »