User:Renee Sweeney/sandbox

Current Research
Most recent work has explored the extensiveness of pleiotropy and its common mechanisms. Although universal pleiotropy was modelled in early research, the advent of Sequencing in the 1970s has allowed molecular geneticists to experiment with gene manipulation and discover a new, more limited model called modular pleiotropy. This assumes that the genome is modular, and genes may affect phenotypes within their module but not in the rest of the organism.

To test this, researchers have attempted to measure the "network diameter," or the number of traits on average affected by a single gene. In a study of the protein interaction networks in Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans, the diameter was found to be about 4-5 edges. Another study used protein sequence and microarray analysis on 321 genes from eight vertebrae species, and averaged 6-7 traits. Quantitative trait analysis on rodent skeletal genetics in a separate study yielded an average of 7.8 affected traits per locus. Although these are merely averages and not direct experimental results, the agreement among these studies provides compelling evidence against universal pleiotropy. Still, however, certain organisms have demonstrated pleiotropy across several modules, such as Pseudomonas fluorescens, whose entire gene network could be rewired by a single nucleotide mutation.

Investigations at the nucleotide level have also shed more light on the mechanisms of pleiotropy. It was concluded that the Catsup gene in the dopamine synthesis pathway is pleiotropic at the gene level, but not at the nucleotide level, which questions the unit of pleiotropic action geneticists should be focusing on. In a study estimating the level of pleiotropy from the genomic sequence data of S. cerevisiae, pleiotropy was found to be highly correlated with protein interaction and biological processes, but not with the number of proteins per gene or molecular functions. This suggests that pleiotropic genes mostly produce single multifunctional products. Two paralogous regulatory genes, zfl1 and zfl2, studied in maize appeared to be associated with the same suite of traits, but each gene was more strongly associated with a subset of those traits, indicating that subfunctionalization may provide an escape from antagonistic pleiotropic traits. Another study which combined comparative methods, sequencing, and enzyme assays on the dihydroflavonol-4-reductase gene of Convolvulaceae came to the same conclusion. The gene had duplicated in some lineages but not others, revealing gene duplication as another escape from detrimental pleiotropic effects.