Opening Darwin's black box: teaching evolution through developmental genetics

When biologists are asked to discuss the evidence for evolution at public forums, they usually use well-established microevolutionary examples. Although these examples show the efficacy of evolution within species, they often leave audiences susceptable to the arguments of creationists who deny that evolution can create new structures and species. Recent studies from evolutionary developmental biology are beginning to provide case studies that specifically address these concerns. This perspective presents some of this new evidence and provides a framework in which to explain homology and phylogeny to such audiences.     

Opening the black box: lessons from cell-free systems on the phagocyte NADPH-oxidase

The NADPH-oxidase complex of phagocytic cells plays a key role in the defense against invading pathogens, through the release of superoxide anion, precursor of other reactive oxygen species (ROS). NADPH-oxidase deficiency is called Chronic Granulomatous Disease (CGD), in which patients suffer from recurrent infections and from the formation of granulomas in various organs. Research on NADPH-oxidase has much benefited from the discovery of cell-free systems, i.e. reconstitution assays from broken resting (unstimulated) phagocytes, in which activation of the oxidase is elicited in vitro. Cell-free systems were developed in parallel to studies of molecular defects of patients with CGD, both approaches leading to the identification of the major proteins implicated in enzyme activation. Variations around the cell-free system allowed molecular dissection of the mechanism of NADPH-oxidase activation and provided insights into its relationship to phagocytosis.     

Franklin and Mesmer: an encounter.

In 1784, as the Enlightenment was on the wane, Paris faced a debate in which reason confronted the supernatural and the mysterious. Dr. Mesmer, a graduate of the medical school in Vienna, had been running a "magnetic clinic" based on the belief that magnetic fluid, flowing from the stars, permeated all living beings and that every disease was due to an obstruction in the flow. By manipulating that fluid, he launched the concept of animal as opposed to mineral magnetism and claimed to cure all ills. This got him into trouble with the medical faculty, and in 1778 he emigrated to Paris, creating secret societies all over France. Six years later, mesmerism was considered a threat, possibly deleterious to both mind and body. Louis XVI appointed two commissions to investigate this likely fraud. Dr. Guillotin headed one; the other, made up of five members of the Academy of Sciences, included an astronomer and was headed by Franklin, American Ambassador to France. Both commissions concluded that the success of mesmerism was due to the manipulation of the imagination. Mesmer protested vigorously but in vain. He left France and died in obscurity in 1815.     

Prioritising health services in an era of limits: the Oregon experience.

How do we decide who should receive the benefits that medical science has to offer? One approach to this decision process, that used by the state of Oregon, is described: who and what are covered, and how health care is financed and delivered, are considered. Oregon''s priorities were set on the basis of broad consensus. The objective of health care reform, it was agreed, is to improve, maintain, or restore health--not universal coverage, access to health care, or cost containment. A Health Services Commission was created to consider clinical effectiveness and, through public involvement, to attempt to integrate social values into the priority list. Oregon''s legislature can use the list to develop an overall health policy which recognises that health can be maintained only if investments in several related areas are balanced.     

Opening the black box: phylogenetics and morphological evolution of the Malagasy fossorial lizards of the subfamily "Scincinae"

The island of Madagascar harbors a highly endemic vertebrate fauna including a high diversity of lizards of the subfamily "Scincinae," with about 57 species in eight genera. Since limb reduction seems to have been a common phenomenon during the evolution of Malagasy "scincines," diagnosing evolutionary relationships based on morphology has been difficult. Phylogenetic analyses of multiple mitochondrial DNA sequences including the entire ND1, tRNA(LEU), tRNA(ILE), tRNA(GLN) genes, and fragments of the 12S and 16S rRNA and tRNA(MET) genes were conducted to test the monophyly of the largest genus Amphiglossus, and to evaluate the various formal and informal species groupings previously proposed for this species-rich group. A further objective was to determine the phylogenetic placements of the several greatly limb-reduced and limbless Malagasy "scincines" and ascertain whether any of these are derived from within the morphologically plesiomorphic Amphiglossus. As limb reduction in skinks is mostly associated with body elongation via an increase in the number of presacral vertebrae, we evaluate the pattern of evolution of the numbers of presacral vertebrae in the context of our phylogeny. We demonstrate that Amphiglossus as currently diagnosed is non-monophyletic, and the species fall into two major groups. One of these groups is a clade that contains the included species of the subgenus Amphiglossus (Madascincus) among other species and is a member of a larger clade containing Paracontias and Pseudoacontias. In the second group, the nominate subgenus Amphiglossus (Amphiglossus) forms several subclades within a larger clade that also contains Androngo crenni and Pygomeles braconnieri, and is sister to Voeltzkowia. All analyses provide strong support for the monophyly of Paracontias and Voeltzkowia. Based on the preferred phylogenetic hypothesis and weighted squared-change parsimony we show that the ancestor of the Malagasy clade was already elongated and had a moderately high number of presacral vertebrae (46-48), which is hypothesized to be the ancestral condition for the whole Malagasy "scincine" clade. We further demonstrate that both multiple increases and reductions of presacral vertebrae evolved in many clades of Malagasy "scincines" and that the use of presacral vertebrae as a major character to diagnose supraspecific units is dubious. Based on our results and published morphological evidence we consider Scelotes waterloti Angel, 1930 to be a junior synonym of Amphiglossus reticulatus (Kaudern, 1922).     

MADS-box out of the black box

The compelling elegance of using genome‐wide scans to detect the signature of selection is difficult to resist, but is countered by the low demonstrated efficacy of pinpointing the actual genes and traits that are the targets of selection in nonmodel species. While the difficulty of going from a suggestive signature to a functional nucleotide polymorphism should not prevent researchers from using genome scans, it does lessen their long‐term utility within and across study systems. In a new study published in this issue of Molecular Ecology ( Mariac et al. 2011 ), researchers have gone a long way towards increasing the relevance of genome‐wide scans for selection via two approaches: (i) they tailored the markers used in the scan to target a family of developmental genes that were good candidates for controlling a trait of interest and (ii) they used an independent mapping population to confirm the association of the gene with polymorphism in the trait of interest. All of this was completed in the nonmodel system of pearl millet (Pennisetum glaucum) and may provide a road map for other researchers hoping to pin down solid candidate genes for selected traits in natural or cultivated systems. Outside of these broad methodological innovations, the paper specifically focuses on a trait (flowering time) that varies across an environmental gradient (rainfall). This environmental gradient potentially serves as a model for environmental change over time, and allele frequencies at the gene can therefore be used to track how populations of pearl millet will adapt to future climate shifts at the genetic level.     

Gene silencing: shrinking the black box of RNAi

The mysterious mechanism whereby the mere presence of double-stranded RNA can inactivate specific genes is yielding its secrets. Recent results identifying cellular components required for RNAi in Caenorhabditis elegans indicate that the mechanism is conserved, ancient and may provide a defense against selfish DNA.     

Opening Pandora's box: the unpredictability of reassurance by a normal test result.

OBJECTIVES--To determine the rate of failure of patient reassurance after a normal test result and study the determinants of failure. DESIGN--Replicated single case study with qualitative and quantitative data analysis. SETTING--University teaching hospital. SUBJECTS--40 consecutive patients referred for echocardiography either because of symptoms (10 patients) or because of a heart murmur (30). 39 were shown to have a normal heart. INTERVENTIONS--Medical consultations and semistructured patient interviews were tape recorded. Structured interviews with consultant cardiologists were recorded in survey form. MAIN OUTCOME MEASURES--Patient recall of the explanation and residual understanding, doubt, and anxiety about the heart after the test and post-test consultation. RESULTS--All 10 patients presenting with symptoms were left with anxiety about the heart despite a normal test result and reassurance by the consultant. Of 28 patients referred because of a murmur but shown to have no heart abnormality, 20 became anxious after detection of the murmur; 11 had residual anxiety despite the normal test result. CONCLUSIONS--Reassurance of the "worried well"-anxious patients with symptoms or patients concerned by a health query resulting from a routine medical examination or from screening-constitutes a large part of medical practice. It seems to be widely assumed that explaining that tests have shown no abnormality is enough to reassure. The results of this study refute this and emphasise the importance of personal and social factors as obstacles to reassurance.