At What Point Do Genes Influence Development?

The Faculty of 1000 is aWeb-based literature awareness tool published by BioMed Central. For more information visit www.facultyof1000.com. Embryonic development doesn't occur by magic; it occurs by predetermined genetic steps leading to production of transcriptional molecules. This process is addressed by two Faculty of 1000-featured papers that deal with unrelated species and cover different manners of viewing gene roles in developmental processes. Nonetheless, the work is related. Kevin White, assistant professor of genetics at Yale University School of Medicine, and his colleagues are focusing on measuring transcript levels, using DNA microarrays that allow rapid and mass screening of the Drosophila genome during different stages of early development.1 "This builds on our previous work, which showed that this approach was useful for studying complex developmental events in Drosophila," says White.2 His earlier investigations identified genes functioning in development that were not known to have such roles; the work also assessed the expression levels of transcript present during different developmental stages in metamorphosis. The current paper follows gene activation and transcript expression throughout the Drosophila life cycle.1 White's team already knew from its previous work that "in Drosophila ... studies suggested that 5000 to 7000 different polyadenylated RNA species are produced at each stage of the life cycle and that the composition of this set of RNAs shifted during development."1 Microarray studies, the group notes, measure the transcript levels of thousands of genes simultaneously. This method has changed how investigators study gene activation during development in the fruit fly. "Not many years ago, a standard molecular genetic study in a model like a fly or mouse was a fill-in-the-blank proposal," says Brian Oliver, who studies Drosophila genetics at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md. This work required the equivalent of mammalian positional cloning to find the gene underlying the phenotype. "Sequenced genomes," he continues, "allow us to skip all this terrible waste of highly trained peoples' time and to get to the question. White's lab is one of two that is providing this transcriptional information in one swoop," says Oliver. Not only does this speed up the process of linking genes to transcriptional products in the species, but it also allows investigators to build regulatory circuits from dynamic expression profiles--a new sort of science, he notes. Michael Purugganan, associate professor of genetics, North Carolina State University, Raleigh, and his colleagues are looking at the interactions between developmental genes in the plant Arabidopsis thaliana and the effects of evolution upon those genes. "For about five or six years now," says Purugganan, "we've been interested in trying to understand how genes that control development have evolved." Unlike White, who is studying thousands of genes simultaneously, Purugganan and colleagues are looking at alleles of six selected developmental genes to study developmental pathways. "Most of these studies look at single genes," says Purugganan. "We became interested in an entire pathway." Purugganan notes that selection works differently on separate genes in the developmental pathway. "There are certain genes that are more prone to adaptive selection," he says. This includes genes that are expressed early in floral development: one called TERMINAL FLOWER1 (TFL1), which is responsible for inflorescence meristem identity, and another called LEAFY (LFY), one of several genes with the role of floral meristem identity. Both genes are important in regulating the identity of the inflorescence and the floral meristem, and both have less polymorphism than other loci for floral development. These genes appear to be related to "timing and spatial patterning of flower and inflorescence branch formation."3 Genes that are responsible for floral organ traits do not seem to have undergone any adaptive evolution. "What we're focusing on," says Purugganan, is to "isolate one group of genes in a life cycle of an organism, not the whole group, and ask how does evolution act at various points." In their paper, Purugganan and colleagues draw a parallel between the types of analyses they are carrying out and the evolutionary analysis of the genes involved in the glycolytic pathways in Drosophila.3 White and colleagues' 1999 paper, in fact, studied the nine genes that encode the enzymes essential for Drosophila's glycolytic pathway; they looked at times of activation and down-regulation resulting from stimulation with the metamorphosis-related hormone, ecdysone. Myrna Watanabe is a freelance writer in Patterson, NY. References 1. M.N. Arbeitman et al., "Gene expression during the life cycle of Drosophila melanogaster," Science, 297:2270-5, Sept. 27, 2002. 2. K.P. White et al., "Microarray analysis of Drosophila development during metamorphosis," Science, 286:2179-84, 1999. 3. K.M. Olsen et al., "Contrasting evolutionary forces in the Arabidopsis thaliana floral developmental pathway," Genetics, 160:1641-50, 2002.

At What Point Do Genes Influence Development?

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