Translational Selection and Molecular Evolution in Drosophila

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This project will combine experimental and computational approaches to demonstrate the role of weak selection in Drosophila genome evolution. Both amino acid-altering and "silent" mutations in protein coding genes may affect the rate and accuracy with which proteins are synthesized. Genome sequence and expression data will be employed to identify amino acids that allow efficient translation. DNA sequence comparisons among close relatives of Drosophila melanogaster will determine whether selection for efficient synthesis acts as a global force in protein evolution. Mutations with subtle effects on cell physiology may play a major role in biological adaptation. However, because the fitness effects of "nearly neutral" mutations lie well outside the range that can be measured directly, comparative DNA sequence analyses may provide the only means of identifying such forces in natural populations. Understanding the forces that constrain protein evolution will inform the design of genes for heterologous expression and DNA vaccination and will aid in identification of homologous proteins in humans and model genetic organisms. This research will also provide opportunities for educators and high school students to conduct summer research projects in genome evolution. In addition, a database of Drosophila DNA sequences will be made publically available.