Tuesday, August 16, 2005

Nature Genetics and the Mid-Atlantic Plant Molecular Biology Society Conference

There is always something interesting in Nature Genetics, but the July issue seems especially rich.

I appreciate this editorial. The advice here (e.g. that postdocs and advisors make a formal plan, and that postdocs ask themselves such questions as "is this the most important scientific question I can ask") is excellent. Anyone considering a postdoc, or taking on a postdoc, should read this.

I am often asked (especially by educated non-scientists in my acquaintance) about genetics and race. This is an old debate and there are excellent sources of information and opinion (including a Social Sciences Research Council forum, a special issue of Nature Genetics and an edited volume by Jefferson Fish; a more complete listing is on Anthropology.net). The bottom line is that race is indeed a social construct. (At least it is very poorly defined within biology, and what biological definitions might be partially valid differ significantly from the way the concept is normally used in our society). The licensing of BiDil specifically for African Americans is therefore troubling. It seems to me that if a drug differs in either safety or efficacy for one "race" or another, then the underlying basis is probably either a genetic difference or a cultural difference. In the first case, the relevant genetic difference itself, or a related biomarker, would be much more reliable than popular notions of race. On the other hand, if the basis is cultural, the relevant practice (such as lifestyle or diet) should be identified. I was therefore gratified to see Nature Genetics publish this letter from Jonathan Kahn making the case against the misuse of race, as well as a sidebar showing how the media has misrepresented their own statements.

Transcriptional Gene Silencing, RNA polymerase IV and siRNAs
The association of specific RNAs (siRNAs) with silenced chromosomes presents something of a paradox (since the siRNAs themselves must be transcribed). This paradox is elegantly resolved by the discovery of "RNA polymerase IV," which is presumed transcribe otherwise silent regions, at least in Arabidopsis (Kanno et al.: "Atypical RNA polymerase subunits required for RNA-directed DNA methylation" Nature Genetics; PubMed; other recent papers cited therein and a News and Views by Vaucheret). In other species RNA polymerase II is implicated (e.g. Schramke et al.) but there may be less siRNA corresponding to silenced loci in those species. On a related note, I was impressed by the massive amounts of MPSS data on Arabidopsis siRNAs presented by Pam Green at the MAPMBS meeting last week. This data includes over 75,000 different siRNA sequences and will soon to be online at http://mpss.dbi.udel.edu/ in a browsable form.

Structural genomic variation within species
One of the insights I came away from last year's MAPMBS meeting with was the idea (Rafalski, MAPMBS2004, PubMed) that "races" of maize show significant variation in gene content due to small (sub megabase scale) structural differences: insertion, deletion and inversion. Although a speaker at this year's meeting expressed the opinion (based on sequence data) that the case in maize may have been overstated, another paper in Nature Genetics (Tuzun et al., Fine-scale structural variation of the human genome; NG; PubMed) reports 297 cases of "intermediate scale" structural variation in a single human individual! It will be interesting to see how this plays out with more time, but SNPs may well be displaced by presence/absence variation as the focus of attention in human genetics. As Charles Lee notes in his News and Views piece, what we see depends on our technology for looking, and I am reminded that a lot of early work in population genetics was based on inversions visible on polytene chromosomes.

No comments: