Ripping someone a new asshole using only a single genome.
You know what I love about science? Someone makes a crackpot claim, and everyone in the research community is there to jump on it and show how back-ass-wards the proposition is. Take, for example this paper that appeared in Nature last year in which the authors propose a new method for detecting natural selection using only a single genome.
Traditional methods for detecting natural selection using DNA sequence data require at least two sequences to be compared. For example, you may have the sequence of a gene responsible for nerve cell development from a human and the homologous gene from a chimpanzee. You hypothesize that evolution of this gene along the human lineage was responsible for some neurological innovation that lead to a cognitive difference between humans and chimps. In order to test your hypothesis, you must determine if natural selection acted on that gene in the human lineage. You could look for an excess number of amino acid substitutions between the two sequences, which would suggest rapid protein evolution along one of the lineages. This type of selection is known as positive selection. Conversely, a deficiency of amino acid changes would suggest purifying selection (selection for constrained function). Importantly, all accepted methods for detecting natural selection rely on comparing multiple sequences.
The new method introduces a metric known as codon volatility, based on the concept of mutational robustness. The authors propose that a gene under strong purifying selection will be robust to mutations that affect its function, and this robustness should be detectable based on the codons present in the gene. More volatile codons (those that are less robust to amino acid changes) should be common in genes under positive selection, whereas genes under purifying selection should have less volatile codons.
When it was first published last April this article raised some eyebrows in my department as many people were skeptical of the methods. Our doubts were confirmed as critiques came pouring in over the past few months from leading researchers at UC Davis, Cornell, Univ of Chicago, Nottingham, South Carolina, Univ of Houston, and Michigan. These articles were published in Nature, Molecular Biology and Evolution, and Genetics. Among the criticisms of the method are that it:
- Ignores effect of codon bias on volatility.
- Is too sensitive to assumption of mutational process and unable to detect positive selection.
- Only detects usage of a amino acids.
- Makes erroneous assumptions regarding the distribution of synonymous substitutions.
- Is not consistent with other, well established, methods for detecting selection.
- And positive selection has no effect on codon volatility in theoretical analyses.
For some reason, Nature loves publishing flashy, yet crappy, science. My favorite Nature faux pas comes from Dancing Naked in the Mind Field by Kary Mullis (the inventor of PCR). In his book he discusses submitting a letter to Nature about astrophysics as a graduate student. He admits that he knew very little about the subject, but it was published none-the-less. After coming up with PCR, he submitted his paper to Nature thinking that an idea that revolutionary would definitely be accepted -- it was not!