Translational Selection and Molecular Evolution in Drosophila

这个项目将结合实验和计算方法来展示弱选择在果蝇基因组进化中的作用。蛋白质编码基因的氨基酸改变和“沉默”突变都可能影响蛋白质合成的速度和准确性。基因组序列和表达数据将被用来识别允许高效翻译的氨基酸。果蝇近亲之间的DNA序列比较将决定选择有效合成是否在蛋白质进化中起到全球作用。对细胞生理有细微影响的突变可能在生物适应中发挥重要作用。然而，由于“近中性”突变的适合度影响远远超出了可以直接测量的范围，比较DNA序列分析可能提供了在自然种群中识别这种力量的唯一手段。了解制约蛋白质进化的力量将为异源表达和DNA疫苗的基因设计提供信息，并将有助于在人类和模式遗传有机体中识别同源蛋白质。这项研究还将为教育工作者和高中生提供机会，开展基因组进化的暑期研究项目。此外，还将公开一个果蝇DNA序列数据库。

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.