Life without transcriptional control? From fly to man and back again

All organisms adapt to changes in their environment by adjustments in gene expression, and in all organisms, from Escherichia coli to man, the most important control point is at transcription initiation. All, that is, except those belonging to one very small family of early‐branching eukaryotes, which seems to have completely lost the ability to regulate transcription by RNA polymerase II. The organisms concerned are unicellular, spindle‐ like flagellates that flourish in the digestive systems of arthropods, in the blood, macrophages and brains of vertebrates from humans to lizards, and even in the sap of coconut palms and lemon trees. Many of them are able to multiply both in a vertebrate (or plant) and an invertebrate, which serves to transmit the parasites from one vertebrate (or plant) to the next. Adaptation to the two distinct environments, with different temperatures, nutrients and defences, requires major changes in gene expression. Yet this seems to be achieved in the total absence of any developmental regulation of RNA polymerase II; perhaps even without any specific polymerase II transcription initiation. This extraordinary state of affairs might be written off as an irrelevant evolutionary quirk (and, indeed, might have even gone unnoticed) if it were not for the fact that some of the organisms concerned, the trypanosomes and the leishmanias, kill millions of people every year (http://www.who.ch). The leishmanias cause a spectrum of diseases ranging from self‐resolving skin ulcers to lethal infection of the internal organs. One‐and‐a‐half to two million people are newly infected every year in the tropics and southern Europe. Leishmania has an extracellular form in the gut of the vector, the sand‐fly, but multiply as spherical aflagellate forms within the lysosomes of mammalian macrophages. Leishmania must be phagocytosed without activating the host macrophage and must combat oxidative, acidic and proteolytic stresses. The South …