Interrogating the role of natural selection in the functional evolution of duplicate genes

当同一基因的多个拷贝被创造并保留在生物体的基因组中时，就会发生基因复制。它被认为通过创造生物特征的创新在进化过程中发挥了关键作用。因此，了解进化如何作用于重复基因将为了解复杂性状和新形态是如何产生的提供关键见解。该项目的主要目标是确定负责在生物体基因组中保留重复基因的进化力量。研究人员将验证一个特定的假设，即功能性重复基因（那些具有新功能的基因）的进化主要是自然选择的结果。长期以来，科学家们一直认为这是事实，但从未能够通过实验验证这一假设。该项目采用了一种创新的方法，首次对这一假设进行了检验。结果将有助于理解生物特征是如何在物种内部和物种之间进化的。该奖项将通过支持本科生和研究生的培训、开源计算机软件的开发以及在开放获取出版物中传播研究成果，对科学界产生多重更广泛的影响。此外，研究人员还将在每年夏天由宾夕法尼亚州立大学主办的Science-U夏令营中为当地K-12学生设计和教授生物信息学和基因组学课程。为这些课程编写的课程也将在一个网站上免费提供给教师。该研究将通过序列和表达水平的方法来研究自然选择对重复基因功能的影响。研究人员最近开发了一种系统发育方法，通过量化密切相关物种中基因表达谱之间的差异来识别具有新功能的重复基因。该方法在果蝇空间基因表达谱中的应用表明，大多数年轻的重复序列具有新的功能，并且新功能的获得发生得很快。相反，在哺乳动物中，大多数年轻的复制体保留了它们祖先的功能，功能分化发生得更加缓慢。在这些谱系中，重复基因之间的功能分化率的对比让人联想到果蝇相对于哺乳动物的更快的序列水平进化。研究人员将验证自然选择在通过重复基因获得新功能方面也起重要作用的假设。研究人员将结合传统的基于序列的测试，以及创新的基于表达的测试，对重复基因进行自然选择。这些分析的目的将是阐明自然选择在重复基因的功能分化中的作用，并检查在不同规模、进化时间和不同水平的功能分化的种群中作用于重复基因的选择力的差异。

Gene duplication occurs when multiple copies of the same gene are created and retained within an organism's genome. It is believed to play a key role in the evolutionary process by creating innovation in organism traits. Therefore, understanding how evolution acts on duplicate genes will provide key insights into how complex traits and novel forms have arisen. The main goal of this project is to determine the evolutionary forces responsible for the retention of duplicate genes in an organism's genome. The researchers will test the specific hypothesis that the evolution of functional duplicate genes (those that have a new function) is primarily a consequence of natural selection. Scientists have long thought this to be the case, but have never been able to experimentally test this hypothesis. This project uses an innovative method that allows this hypothesis to be tested for the first time. Results will help to understand how organism traits evolve within and among species. The award will have multiple broader impacts on the scientific community by supporting the training of undergraduate and graduate students, development of open source computer software, and dissemination of research findings in open access publications. Additionally, the researchers will design and teach courses on bioinformatics and genomics to local K-12 students at the Science-U camp hosted by Pennsylvania State University each summer. Curricula developed for these courses will also be made freely available on a website for teachers.The proposed research will examine the impact of natural selection on duplicate gene functions via both sequence- and expression-level approaches. The researchers recently developed a phylogenetic approach for identifying duplicate genes with novel functions by quantifying differences between their gene expression profiles in closely related species. Application of this method to spatial gene expression profiles in Drosophila revealed that most young duplicates possess new functions, and that acquisition of new functions occurs rapidly. Conversely, in mammals, most young duplicates retain their ancestral functions, and functional divergence occurs more gradually. The contrast in functional divergence rates between duplicate genes in these lineages is reminiscent of the faster sequence-level evolution observed in Drosophila relative to mammals. Researchers will test the hypothesis that natural selection also plays an important role in acquisition of new functions by duplicate genes. Researchers will apply a combination of traditional sequence-based, as well as innovative, expression-based tests for natural selection on duplicate genes. The objectives of these analyses will be to elucidate the role of natural selection in functional divergence of duplicate genes, and to examine differences in selective forces acting on duplicates in populations of different sizes, over evolutionary time, and with varying levels of functional divergence.