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 »
Auteurs : Randolph M. Nesse et George C. Williams, traduit de l’anglais par Maude Bernardet.
Éditions De Boeck, octobre 2013 ISBN : 978-2804181710
Ouvrage fondateur de la médecine darwinienne, initialement paru en 1994, Pourquoi
tombons-nous malade ? reste le livre de référence de ce champ disciplinaire. George Williams et Randolph Nesse en exposent de manière accessible les principes, mettant en perspective l’histoire évolutive des humains pour comprendre l’émergence des maladies. Les auteurs soulèvent notamment le fait que de nombreux aspects des maladies sont en fait des effets collatéraux du processus évolutif : défenses du corps, compromis coûts-bénéfices dans les fonctions de nos corps, legs historiques, changement de notre environnement plus rapide que le processus évolutif lui-même.
Les sujets abordés sont nombreux, allant du principe de la course aux armes avec les agents infectieux aux implications que la prise en compte du phénomène de l’évolution peut avoir sur la recherche et la pratique de la santé, en élargissant la réflexion sur le vieillissement, les interactions intra-familiales et en considérant d’un abord nouveau les troubles psychiatriques.
L’écriture est illustrée de manière concrète, rendant le livre abordable pour les non scientifiques et son contenu stimulant pour la réflexion des spécialistes. Continue Reading »
By Edward H. Morrow and Tim Connallon. In Evolutionary Applications 4 SEP 2013 DOI: 10.1111/eva.12097 (open access)
Mutation and selection are thought to shape the underlying genetic basis of many common human diseases. However, both processes depend on the context in which they occur, such as environment, genetic background, or sex. Sex has widely known effects on phenotypic expression of genotype, but an analysis of how it influences the evolutionary dynamics of disease-causing variants has not yet been explored. We develop a simple population genetic model of disease susceptibility and evaluate it using a biologically plausible empirically based distribution of fitness effects among contributing mutations. The model predicts that alleles under sex-differential selection, including sexually antagonistic alleles, will disproportionately contribute to genetic variation for disease predisposition, thereby generating substantial sexual dimorphism in the genetic architecture of complex (polygenic) diseases. This is because such alleles evolve into higher population frequencies for a given effect size, relative to alleles experiencing equally strong purifying selection in both sexes. Our results provide a theoretical justification for expecting a sexually dimorphic genetic basis for variation in complex traits such as disease. Moreover, they suggest that such dimorphism is interesting – not merely something to control for – because it reflects the action of natural selection in molding the evolution of common disease phenotypes. Full article here.
Abstract: W.D. Hamilton was most known for his work on two topics: social evolution and parasites. Although at first glance these seem to be disparate interests, they share many attributes and have logical connections within evolutionary biology. Nevertheless, Hamilton’s contributions in these areas met with very different receptions, with his place in the field of social evolution assured, but his work on the role of parasites perceived as more specialized. We take an historical approach to examine the reasons for this difference.
The article provides evidence for positive selection for a mutation in p53, KITLG, that causes testicular cancer. They note that this same allele influences the rate of replication of melanin producing cells in response to UV radiation. This allele is much more common in Caucasians than Africans, and testicular cancer is 4-5 times more common in Caucasian men. Continue Reading »
In the eyes of some scientists, anxiety disorders have evolved from primitive human instincts, and examining their histories is crucial for medicine today.
This is the basis of evolutionary medicine, an emerging field of biology and the subject material of a new minor now offered at UCLA.
Evolutionary medicine looks at modern medicine through an evolutionary and historical perspective, said Daniel Blumstein, chair of the UCLA Department of Ecology and Evolutionary Biology and program director of the evolutionary medicine minor. Read more
Abstract: We describe in detail the abnormal chromosomes of HEL, a human leukaemia
cell line grown in many laboratories. Complementary high resolution and
whole chromosome analysis tools, including the localisation of repetitive
DNA sequences on intact chromosomes, are essential for understanding
genome remodelling and evolution in cancer cells.
How effectively can HIV phylogenies be used to measure heritability?
Parasite Immunology published a Special Issue October 10th on The Evolutionary Biology of Host Defence, with 7 articles and an overview editorial by Andrea Graham. This will be required reading for all who study evolution and infection. The articles are linked below, but they are unfortunately not open access.
A central focus of recent research aimed at developing a vaccine for HIV-1 is the identification of potent broadly-neutralizing antibodies (bNAbs). Due to work from several laboratories, many such antibodies have now been identified, produced in quantity as monoclonal antibodies, and characterized with respect to key properties such as epitope specificity, affinity for the corresponding HIV-1 epitope, and neutralizing activity against many strains of varying susceptibility to antibody-mediated inactivation (important examples of these publications are: Scheid et al., 2009; Walker et al., 2009; Wu et al., 2010; Walker et al., 2011; Huang et al., 2012). These successes notwithstanding, the scale of the challenge facing the vaccine developers is clarified by the following facts: 1) potent bNAbs only develop in 10-30% of infected individuals, 2) it typically takes between two and three or four years after initial infection for these antibodies to appear in the blood of these individuals, and 3) antibodies with the desired attributes often have extraordinary numbers of somatic mutations in the variable domains that mediate binding to the HIV-1 antigen (Klein et al., 2013a). A study (Klein et al., 2013b) published earlier this year from the laboratory of Michel Nussenzweig both illuminates one possible factor accounting for the impressive length of time and number of mutations associated with the generation of potent bNAbs and provides an extraordinary example of the power of intense selection to confound expectations arising from previously observed associations. In this instance, the undermined expectations related to the well-established functional correlates of hypervariable and framework regions within antibody variable domains. Continue Reading »
Evolution has never been a value-free idea. Ultimately, it has always been all about us. It started in the early Eighteenth Century as an epiphenomenon on the new philosophy of progress. The Ancient Greeks did not really have an idea of historical change and certainly not one of upwards climb. Plato’s Republic, for example, saw rise and development and then decay and decline. People are often surprised that, having built an ideal state, then at the end of the book Plato sets about letting it fade and whither. This was bound to be. For him, this world of ours is one of change and lack of permanence. Nothing lasts, not even the best. At most, history is like a sine curve, up and down endlessly. True stability is to be found only in the rational world, the world of Forms. Continue Reading »
The effect of artificial light on melatonin and circadian rhythms has been uncertain. This small study shows dramatic differences resulting from artificial vs natural light exposure.
Wright, Kenneth†P, McHill, Andrew†W, Birks, Brian†R, Griffin, Brandon†R, Rusterholz, Thomas, & Chinoy, Evan†D. (2013). Entrainment of the Human Circadian Clock to the Natural Light-Dark Cycle. Current biology : CB, 23(16), 1554-1558. Link here, not open access
Summary: The electric light is one of the most important human inventions. Sleep and other daily rhythms in physiology and behavior, however, evolved in the natural light-dark cycle , and electrical lighting is thought to have disrupted these rhythms. Yet how much the age of electrical lighting has altered the human circadian clock is unknown. Here we show Continue Reading »
Currently, I am on vacation near the beach in South Carolina. Consequently, I have opted for a topic that is bit different than the majority of my monthly commentaries in that it focuses not on a recent original report but instead on a conceptual point made in a book over thirty years ago. Nevertheless, after a somewhat less strictly scientific diversion I will come to the central idea at issue, which is arguably the premier exemplar of the relevance of evolutionary principles to the operation of the immune system on short time scales, by which I refer to the concept of clonal selection. But first, we make a foray into the world of magazine publishing and the niche within that domain focusing on the arguably more intellectual readers. Continue Reading »
Funkhouser LJ, Bordenstein SR (2013) Mom Knows Best: The Universality of Maternal Microbial Transmission. PLoS Biol 11(8): e1001631. doi:10.1371/journal.pbio.100163 (Open Access)
The sterile womb paradigm is an enduring premise in biology that human infants are born sterile. Recent studies suggest that infants incorporate an initial microbiome before birth and receive copious supplementation of maternal microbes through birth and breastfeeding. Moreover, evidence for microbial maternal transmission is increasingly widespread across animals. This collective knowledge compels a paradigm shift—one in which maternal transmission of microbes advances from a taxonomically specialized phenomenon to a universal one in animals. It also engenders fresh views on the assembly of the microbiome, its role in animal evolution, and applications to human health and disease.
The evolution of resistance in Staphylococcus aureus occurs rapidly, and in response to all known antimicrobial treatments. Numerous studies of model species describe compensatory roles of mutations in mediating competitive fitness, and there is growing evidence that these mutation types also drive adaptation of S. aureus strains. However, few studies have tracked amino acid changes during the complete evolutionary trajectory of antibiotic adaptation or been able to predict their functional relevance. Here, we have assessed the efficacy of computational methods to predict biological resistance of a collection of clinically known Resistance Associated Mutations (RAMs). We have found that >90% of known RAMs are incorrectly predicted to be functionally neutral by at least one of the prediction methods used. Continue Reading »
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: Continue Reading »