Mammalian melanism: natural selection in black and white Michael E.N. Majerus and Nicholas I. Mundy
Trends in Genetics 10.1016/S0168-9525(03)00257-9
Two recent papers on the molecular basis of melanism strengthen the chain of evidence linking
genotype and phenotype in nature. Research on coat colour polymorphisms in rock pocket mice from
differently coloured rock substrates provides a compelling example of the genetics of adaptation and
the serendipitous nature of darwinian selection. Mutations in one gene, melanocortin-1-receptor, are
perfectly associated with dark coat colour on black lava. Comparative sequence analysis shows that
the same gene is involved in melanic polymorphism in some cats.
Melanism is a ubiquitous phenomenon in the animal kingdom and has long been used to investigate
evolutionary change. The melanic forms of peppered moth, Biston betularia, and other insects, that
have arisen or spread since industrialization, provide some of the best examples of darwinian
evolution in the wild. However, the genes responsible for these melanic forms have not been
identified. Thus, the crucial step of connecting genotype with phenotype for an adaptive trait has
not been accomplished in these classical cases of darwinian evolution in action. Indeed, this link
has been made in remarkably few instances, and most of those involve traits under strong selection
caused by human influence: pesticide resistance in insects and rats, antibiotic resistance in
bacteria and heavy metal tolerance in plants. Now, Michael Nachman, Hopi Hoekstra and Susan
D'Agostino, from the University of Arizona, have provided the genotype-phenotype link for an
adaptive trait in a natural population of mice in which selection is not influenced by humans: this
is the story of the melanic rock pocket mouse.
Read the rest at BioMedNet gateways.bmn.comarticleOpen ↗
Folding for binding or binding for folding? Amedeo Caflisch
Trends in Biotechnology 2003, 21:423-425
A number of proteins are partially unstructured under physiological conditions and assume a well-
defined three-dimensional structure only upon binding to another protein or macromolecular
complex. Numerous examples have been found, especially among proteins involved in regulatory
functions in eukaryotic cells. Recent computer simulations by Verkhivker et al. yielded an atomic-
detail picture of the folding of p27 and its concomitant binding to the phosphorylated cyclin A-
cyclin dependent kinase 2.
The biological function of a protein is strictly related to its three-dimensional structure in the
folded state. This is a dogma in molecular biology that might have to be slightly refined because
recent experimental evidence indicates that there are soluble proteins that lack a well-defined
folded structure, or contain disordered segments [1,2] . A computational approach focused on known
proteins with intrinsic disorder has predicted unstructured regions of 40 or more consecutive
residues in 36-63% of the genome of five eukaryotes [3]. Some of these might be false positives
(e.g. long loops distant from the active site or binding site in otherwise rigid enzymes or
receptors), yet these high frequencies of occurrence are significant. In their recent
simulation study, Verkhivker et al. [4] investigated the coupled folding and binding of p27 to
the cyclin A-cyclin dependent kinase 2 (CDK2) complex, which is involved in cell cycle
regulation. Their analysis yields an atomic picture of the transition state ensemble (TSE) and
the sequence of events for folding and binding.
Kind Regards, Robert Karl Stonjek.