A Simple Screen to Identify Promoters Conferring High Levels of Phenotypic Noise

Genetically identical populations of unicellular organisms often show marked variation in some phenotypic traits. To investigate the molecular causes and possible biological functions of this phenotypic noise, it would be useful to have a method to identify genes whose expression varies stochastically on a certain time scale. Here, we developed such a method and used it for identifying genes with high levels of phenotypic noise in Salmonella enterica ssp. I serovar Typhimurium (S. Typhimurium). We created a genomic plasmid library fused to a green fluorescent protein (GFP) reporter and subjected replicate populations harboring this library to fluctuating selection for GFP expression using fluorescent-activated cell sorting (FACS). After seven rounds of fluctuating selection, the populations were strongly enriched for promoters that showed a high amount of noise in gene expression. Our results indicate that the activity of some promoters of S. Typhimurium varies on such a short time scale that these promoters can absorb rapid fluctuations in the direction of selection, as imposed during our experiment. The genomic fragments that conferred the highest levels of phenotypic variation were promoters controlling the synthesis of flagella, which are associated with virulence and host–pathogen interactions. This confirms earlier reports that phenotypic noise may play a role in pathogenesis and indicates that these promoters have among the highest levels of noise in the S. Typhimurium genome. This approach can be applied to many other bacterial and eukaryotic systems as a simple method for identifying genes with noisy expression

Genetics of the cell surface

The surface of a cell is one of its most important components through which it can communicate with the outside environment, and with other cells. The aim of this volume is to illustrate the contributions made by genetics to the understanding of some important cell surface phenomena. The first series of four contributions deals with a variety of examples of cell-surface genetics from bacteria through to man. The genetics of the bacterial surface provides an interesting model for higher organisms, including problems of transport and cellular interaction. The red cell blood groups, which provided the first example of a clearly defined genetic difference on any cell surface, were also the first such variations whose biochemical basis was clearly established. The remarkable cell surface variants of the trypanosomes must have a genetic basis, whose nature remains a challenge to the molecular geneticist. The last of these four contributions deals with plant incompatibility systems, whose physiology has long suggested mechanisms involving some form of surface recognition. The second set of four contributions concentrates on the functions, genetics, and biochemistry of the major histocompatibility systems of mouse (H-2) and man (HLA). These systems, which have their counterparts in many other species, are now known to encompass a large number of genes controlling cell surface determinants, immune response differences and components of the complement system