果蝇中多态新复制基因的鉴定、选择压力分析和功能研究

Ever-increasing evidence shows that new genes generally arise via gene duplication and they can drive phenotypic evolution. Previous studies of new genes usually used comparative approaches between species and mainly focused on fixed genes. In recent years, several studies about polymorphic (non-fixed) new genes have emerged, which were based on the second generation sequencing (Illumina) technology. However, since the read length of Illumina platform is too short, the exact sequence and structure of duplicated new genes are unknown. Thus, whether these genes emerge under the adaptive force and what kind of functional role they play remains less studied. In this proposal, we plan to use Drosophila as a model organism and perform the following studies: 1) to identify and annotate polymorphic new duplicated genes based on the PacBio (long read) sequencing; 2) to infer the selection force of new genes and examine whether their emergence is consistent with neutral theory of evolution; 3) to study the functions of a few new genes and understand how a polymorphic new gene integrates into a preexisting genetic network and shapes phenotypic difference among populations. This proposal (if funded) will help to set up a long read based new research paradigm of polymorphic duplicated genes, and the result will be helpful to interpret within-species polymorphism data of other species.

新基因多来源于基因复制，它们是表型演化的重要推动力。传统的新基因研究多通过物种间的比较进行，关注已固定的新基因。近年来，在二代测序等技术基础上，尚未固定的新基因研究在群体水平上逐步展开。然而二代数据读长短，基于此的研究无法确定新复制基因的序列和结构，从而导致这些多态新基因的选择压力分析和功能研究无法深入开展。本项目拟以果蝇群体为研究对象进行以下工作，首先基于三代长读长基因组和转录组数据鉴定、注释尚未固定的新复制基因；其次对这些新基因进行选择压力分析；随后通过实验研究来探索若干新基因个案的功能和作用机制。基于上述工作来探讨如下问题：（1）新复制基因的产生是否符合中性进化理论？（2）新复制基因如何发挥功能，导致不同群体的表型差异？本项目有助于推广基于三代测序数据研究物种内多态新基因的新范式，其结果可为解读其他物种的群体多态数据提供参考依据。

本项目鉴定了果蝇群体中尚未固定的新重复基因，探索了其起源机制和功能，分析了其选择压力；同时我们将分析扩展到其他动物类群。主要研究成果包括：1)刻画了果蝇和人类多态性基因转录水平的演化；2)发现基于转座子的重复基因起源机制；3)发现了执行不可缺少的人类特异的调控红细胞发育功能的重复基因；4)构建了GenTree数据库，鉴定了灵长类特异基因与人类特异蛋白编码基因。5)研究了雪雀的高原适应进化史；6）通过分析果蝇中核心基因的年龄分布，探索了基因型-表型网络演化机制。综上所述，我们共计发表了7篇SCI文章，其中6篇在著名期刊发表，申请专利2项，培养博士研究生6人，硕士研究生2人，出站博士后1人。