The genetic control of common traits is rarely deterministic, with many genes contributing only to the chance of developing a given phenotype. This incomplete penetrance is poorly understood and is usually attributed to interactions between genes or interactions between genes and environmental conditions. Because many traits such as cancer can emerge from rare events happening in one or very few cells, we speculate an alternative and complementary possibility where some genotypes could facilitate these events by increasing stochastic cell-to-cell variations (or ‘noise’). As a very first step towards investigating this possibility, we studied how natural genetic variation influences the level of noise in the expression of a single gene using the yeast S. cerevisiae as a model system. Reproducible differences in noise were observed between divergent genetic backgrounds. We found that noise was highly heritable and placed under a complex genetic control. Scanning the genome, we mapped three Quantitative Trait Loci (QTL) of noise, one locus being explained by an increase in noise when transcriptional elongation was impaired. Our results suggest that the level of stochasticity in particular molecular regulations may differ between multicellular individuals depending on their genotypic background. The complex genetic architecture of noise buffering couples genetic to non-genetic robustness and provides a molecular basis to the probabilistic nature of complex traits.

Twenty-seven microsatellite loci were used to define genetic variation and relationships among eight Indian riverine buffalo breeds. The total number of alleles ranged from 166 in the Toda breed to 194 each in the Mehsana and the Murrah. Significant departures from the Hardy-Weinberg equilibrium were observed for 26 locus-breed combinations due to heterozygote deficiency. Breed differentiation was analysed by estimation of F(ST) index (values ranging from 0.75% to 6.00%) for various breed combinations. The neighbour-joining tree constructed from chord distances, multidimensional scaling (MDS) display of F(ST) values and Bayesian clustering approach consistently identified the Toda, Jaffarabadi, and Pandharpuri breeds as one lineage each, and the Bhadawari, Nagpuri, Surati, Mehsana and Murrah breeds as admixture. Analysis of molecular variance refuted the earlier classification of these breeds proposed on the basis of morphological and geographical parameters. The Toda buffaloes, reared by a tribe of the same name, represent an endangered breed from the Nilgiri hills in South India. Divergence time of the Toda buffaloes from the other main breeds, calculated from Nei's standard genetic distances based on genotyping data on seven breeds and 20 microsatellite loci, suggested separation of this breed approximately 1800-2700 years ago. The results of the present study will be useful for development of rational breeding and conservation strategies for Indian buffaloes.