PNAS Early Edition highlights 20060712
PNAS publish their own This Week In PNAS Early Edition but below the fold are my picks from the latest batch, which include unanticipated difficulties in finding the molecular genetics that keep voles bonded for life, unexpected complexity in the molecular genetics underlying a single gene disorder, and what happens when you push birds through a bottleneck (answer: they come out more like chickens).
[Published: 12-Jul-06 | Permalink | Category: In response | Comments]- Lim and coworkers in 2004 reported a single gene effect on monogamy in a mammal: alterations of the arginine vasopressin 1a receptor turned randy, outcrossing male prairie voles into stay-at-home, help-with-the-washing-up partners-for life. This was based on a simple (n=4) finding - two species of monogamous voles had short tandem repeats in that gene's promoter, two promiscuous ones didn't. Speculation on the human applications was, naturally, rife. Now Fink and co (doi: 10.1073/pnas.0602380103) show that the results are (sadly, fortunately) not generalisable. They cast a broader net (n=21) and found that not only does the correlation fail but that the STRs are more common than monogamy, an admittedly rare strategy among mammals even where an effort is made. The effects of vole gene therapy on the contribution to remembering anniversaries etc. are more likely to be cascading from multiple epistatic changes. There is, as yet, no gene therapy-based technical quick-fix to ensure men stay where they're put - you must continue to use the usual means.
- Will chickens survive being pushed through a bottleneck? Pimm and coworkers (doi: 10.1073/pnas.0604181103) report that conservation makes a difference to bird species survival, because the observed rate of extinction for birds since 1975 is a merely shocking 50 extinctions per million species per year (MSY) as opposed to their extrapolation of early twentieth century rates i.e. it could have been 150 E/MSY. That's a big number. For comparison, 1 MSY = 1 of the 10,000 known bird species gone forever per century, allegedly the prehistoric rate (alleged, because it's based on the fossil record and therefore undersamples). They give plenty reasons why the numbers are hard to calculate (skewed data, uncertainty around preliterate and prehistoric extinctions, inconsistent underreporting) and why it will anyway become easier to count bird species numbers (because they're trending to zero). Species with human utility will of course survive, so I expect that whoever inherits the Earth a million years hence will find in their fossil record a period one million years earlier when avians passed through a bottleneck and then radiated from a small number of chicken-like founders. Perhaps they will postulate vivid hypotheses as to why large numbers of species crashed over so short a time. We can feel smug: we know the answer: it's us. Chuck another passenger pigeon on the barbie, will ya?
- This month it's trendy to claim (with some justification) than the amyloid hypothesis is overly simplistic. Nature Medicine did a special on it (all behind a paywall, even the accompanying Nature News story, so I won't link any deeper) and PNAS has two papers from Susan Lindquist's group. The first (doi: 10.1073/pnas.0604547103) shows that peptide sequences flanking the polyglutamine region are important. While having a string of 39 glutamines in exon 1 of your huntingtin protein might put you on the cusp of Huntington's Chorea, other parts of the protein can affect the aggregation and therefore, probably, the progression and pathology of the disease. Some short motifs help (they discourage aggregation, or make it so tight that the apparent toxicity is lowered); other hurt (they make aggregation more likely, more successful, and more toxic). There is a certain amount of unexplained variability in pathology between patients with identically long polyQ regions that this work may explain. The second paper (doi: 10.1073/pnas.0604548103) uses the same model and shows that the effect on aggregation of flanking regions is further modulated by levels of other proteins rich in glutamine residues. Which makes sense: polyQ genes are expressed in lots of places (as are, say, prions) yet only aggregate and devastate in brains where, presumably, dangerously high levels of other glutamine-containing peptides, perhaps vital for subsequent function, are sufficient for the disease to kick off. Another certainty lost[64].
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