The proposed work asks, "Why do some traits persist apparently unchanged for long periods of evolutionary time?" One possibility is that this is due to exquisite conservation of individual genetic programs that direct development. However, evidence indicates that in many cases individual developmental regulators have functionally diverged even between fairly closely related species. An alternative explanation is that changes may accumulate without causing morphological differences if they compensate or "buffer" each other. This proposal will dissect specific molecular mechanisms responsible for the evolution of compensatory changes in the case of a single gene between two model worms, C. elegans and C. briggsae, and test the generality of the findings using a number of co-expressed genes in a variety of related nematodes. Since regulatory evolution is thought to be an important driving force of morphological evolution, this work will be of interest to a broad community of Evo-Devo researchers.
Broader Impacts: Dr. Ruvinsky incorporates findings of this work into his teaching of undergraduate and graduate students at the University of Chicago as well as to science teachers of Chicago Public Schools. Research in Dr. Ruvinsky's laboratory will involve undergraduate and graduate students who will be trained in experimental and computational approaches central to this proposal. The PI and other members of the laboratory will present their findings at a variety of scientific meetings.
Descent with modification from common ancestors unites all forms of life on Earth. Therefore, examining features shared by organisms promises to reveal functional elements of biology that have been retained over long periods of time; these are likely to be important. We applied this rationale to understanding how gene regulation has evolved. We carried out this work in a model species C. elegans, that permitted a range of precise experimental manipulations. We made several important discoveries that have now been published in open-access journals. First, in many instances even though expression patterns of certain genes are indistinguishable between closely related species, the mechanisms that direct these patterns have nonetheless diverged. Second, we dissected one such mechanism and found that it is due to compensatory evolution between gene regulatory sequences and transcription factors that bind to them. Third, we demonstrated that even though the regulatory sequences of genes have experienced accelerated rate of evolution, it does not mean they have evolved new functions. In some cases, this just reflects a profound restructuring of the genetic programs that control gene expression. Computational genome scans for regions of accelerated divergence are commonly used to identify genes involved in novel functions, but our results argue that this should be done with far greater caution. Fourth, we discovered a new molecular mechanism which makes gene expression robust, that is, relatively insensitive to fluctuations in environmental conditions. Our results improve the understanding of gene regulatory evolution and comparative genomics, the effort to infer sequence functions from cross-species comparisons. Importantly, this project served to train several young scientists, including members of traditionally underrepresented minorities. They are now pursuing advanced careers in STEM fields. In the course of this work we also engaged broader public, by reaching out to high school biology teachers and students and engaging them in science via teaching, laboratory demonstrations, and conducting research.
