Possible Degeneracy in Genotype-Phenotype Relationships due to DNA-RNA Sequence Disparity

An assumption fundamental to medical genetics is that the DNA sequence of an allele at a particular locus will (in the vast majority of instances) be faithfully transcribed into RNA and translated into protein.  This assumption has been largely accepted in spite of known rates of transcriptional and translational errors as well as special cases of RNA editing, in which enzymes alter the RNA sequence post-transcriptionally in ways that can influence translation.  If DNA-RNA-peptide sequence fidelity were reduced to zero, it would not be worth attempting to correlate genotype and phenotype.  More fundamentally, traits would not be heritable, thereby abrogating a necessary condition for Darwinian evolution.

 Therefore, the recent study by Li et al., in Science (2011) is of substantial interest.  The authors document numerous differences (still a minority) between DNA sequences and the putatively corresponding RNA sequences (referred to by the authors as RNA-DNA differenes or RDDs). (more…)

Do we expect the body to be a “One Hoss Shay”?

In an 1858 humorous poem The Deacon’s Masterpiece, or the Wondeful One Hoss Shay, Oliver Wendell Holmes Sr. described a carriage so artfully constructed as to have no weakest link. The carriage ran smoothly for exactly a hundred years, and then one day

it went to pieces all at once, –
All at once, and nothing first, –
Just as bubbles do when they burst,

leaving its driver sitting atop a pile of rubble and dust.

(more…)

The Hygiene Hypothesis and Darwinian Medicine–Book Review

A constructively critical appraisal of the hygiene hypothesis in evolutionary perspective

Book Review: The Hygiene Hypothesis and Darwinian Medicine
Graham A.W. Rook, Editor,Progres  s in Inflammation Research, Michael J. Parnham, Series Editor
Birkhäuser Verlag AG, Basel, Boston, Bern       ISBN 978-3-7643-8902-4

The hygiene hypothesis (David Strachan, Brit Med J 299:1259-1260, 1989) has done much to literally bring immunology into household conversations, in a meaningful and practical way. How should we balance the risk of acutely dangerous infections in our babies and toddlers with a supposedly healthy exposure to environmental microbes and non-infectious agents to limit the lifetime risk of asthma and autoimmune disease? (more…)

The disappearing human microbiota

What are the consequences of the disappearing human microbiota?
by Martin J. Blaser and Stanley Falkow
in Nature Reviews Microbiology   doi:10.1038/nrmicro2245

Who are we? From prions and organelles up through neighborhoods and nation-states, we are groups of groups of groups. In this thoughtful, provocative paper Blaser and Falkow remind us that 90% of our cells are non-human. Vertebrates coevolved with vast communities of microorganisms with whom they share complex endosymbiotic relationships. The authors assert that the human microbiome has been dramatically altered by changes in human ecology. They expand on their disappearing microbiota hypothesis, using the decreasing prevalence of Helicobacter pylori as an example, and argue that such alterations have physiologic and clinical consequences that must be better understood.

Mark D. Schwartz, MD
Associate Professor of Medicine
NYU School of Medicine

Abstract:
Humans and our ancestors have evolved since the most ancient times with a commensal microbiota. The conservation of indicator species in a niche-specific manner across all of the studied human population groups suggests that the microbiota confer conserved benefits on humans. Nevertheless, certain of these organisms have pathogenic properties and, through medical practices and lifestyle changes, their prevalence in human populations is changing, often to an extreme degree. In this Essay, we propose that the disappearance of these ancestral indigenous organisms, which are intimately involved in human physiology, is not entirely beneficial and has consequences that might include post-modern conditions such as obesity and asthma.

Early Development and Reproductive Health (Workshop report)

Early Development and Reproductive Health in Later Life

One of five workshops in a conference on
Evolution and Diseases of Modern Environments
Organized by Randolph Nesse, at the Berlin Charité,  October 13-14, 2009
In conjunction with The World Health Summit
Sponsored by the Volkswagen Foundation

Session leaders: Gillian Bentley and Grazyna Jasienska

In session: Gillian Bentley, Benjamin Campbell, Kathryn Clancy, Marco Del Giudice, Vivette Glover, Grazyna Jasienska, Diana Kuh, Shanthi Muttukrishna, Pablo Nepomnaschy, Alejandra Nuñez de la Mora, Janet Rich-Edwards, Norah Spears, Hamish Spencer, Beverly Strassmann, John Wiebe

Raporteurs: Kathryn Clancy and Benjamin Campbell

In evolutionary medicine so far, a lot of emphasis has been placed on understanding disease, and with the exception of cancer reproductive function is especially understudied. We want to look at the relationship between early development and adult reproduction but we have little data. Those of us in this session have an evolutionary, ecological perspective but few have also thought about a broader health perspective to combine both disciplines. Preliminary discussions identified nutritional status and psychosocial stress as crucial to this combined perspective, and could provide a direct link to evolutionary medicine.

We first sought to define “stress” (more…)