CAREER: Reproductive mode and horizontal gene transfer in nematode worms: Training early career researchers in computational evolutionary biology

生物体的DNA来自两个来源：(A)从双亲遗传给后代，(B)来自其他生物的横向或水平基因转移(HGT)。HGT在真核生物中的进化意义是生物学中一个基本的悬而未决的问题。在下一代基因组测序出现之前，HGT被认为在微生物中很常见，但仅限于具有内共生体和寄生虫的真核生物。过去十年发表的研究结果表明，在真核生物中，古代和最近的水平转移可能都是常见的，但由于组装的基因组序列中的污染问题，以及缺乏在整个基因组中识别HGT的适当方法，这些科学问题的研究一直受到阻碍。关于HGT在真核生物进化中最重要的问题是：(A)HGT的可能性如何取决于生物体的生态和生活史？以及(B)HGT对进化有什么影响？该项目将开发解决这些问题所需的方法，并分发免费可用的软件包，使其他科学研究人员能够使用这些方法来识别HGT。将为50种线虫物种制作参考基因组序列和基因注释，这些数据将通过WormBase和国家生物技术信息中心序列读取档案公开。该项目将通过阿拉巴马大学新的、创新的、有指导的夏季研究经验，通过培训早期职业科学家进行计算生物学和科学研究，将研究和教育结合在一起。自我繁殖和无性繁殖的进化影响物种遗传学的重要方面，包括遗传变异的水平。有性繁殖通过重组产生新的遗传变异，并影响生物进化的方方面面。因此，自我繁殖和无性繁殖可能会对HGT产生影响，因为这些有机体可能会利用HGT产生变异。相反，由于内共生体和寄生虫，雄性和雌性分开的异交生物可能会受到HGT的影响。该项目采用了一种独特的创新方法来研究线虫门中HGT与生殖模式的关系，并将导致建立一个将生殖模式与HGT联系起来的概念性框架。这些发现将促进对HGT在真核进化中的意义和作用的理解。HGT衍生基因的研究将在功能的背景下进行，这些结果将有助于理解环境选择塑造真核基因组中HGT衍生基因的模式。这项研究将导致关于生殖模式和HGT如何塑造基因组进化的重要发现，并为更广泛的科学理解进化过程如何塑造基因组模式提供新的见解。为了实现这些目标，该项目有四个具体目标：(1)开发生物信息学方法，在从头测序项目中分离污染物和真实的HGT；(2)开发在组装的基因组序列中识别HGT的概率方法；(3)利用系统发育比较方法分析异交、自交和无性生物中的HGT；以及(4)为本科生开发一个新的创新夏季研究项目，阿拉巴马大学的计算研究经验(CRE@UA)。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

An organism’s DNA comes from two sources: (a) inheritance from parents to offspring, and (b) lateral or horizontal gene transfer (HGT) from other organisms. The evolutionary significance of HGT in eukaryotes is a fundamental open question in biology. Prior to the advent of next-generation genome sequencing HGT was thought to be common in microbes but limited to eukaryotes with endosymbionts and parasites. Published findings over the last ten years have suggested that both ancient and recent horizontal transfer may be common in eukaryotes but pursuing these scientific questions has been hampered by contamination problems in assembled genome sequences and a lack of appropriate methods for identifying HGT across entire genomes. The most significant questions regarding HGT in eukaryotic evolution are now: (a) How does the likelihood of HGT depend on an organism’s ecology and life history?; and (b) What are the consequences of HGT for evolution? This project will develop the methods necessary to pursue these questions, and distribute freely available software packages that will enable other scientific researchers to use these methods to identify HGT. Reference genome sequences and gene annotations will be produced for 50 nematode species and these data will be made publicly available through WormBase and the National Center for Biotechnology Information Sequence Read Archive. This project will integrate research and education by training early career scientists in computational biology and scientific research through a new, innovative mentored summer research experience at the University of Alabama.The evolution of self-fertility and asexuality affects important aspects of a species genetics including levels of genetic variation. Sexual reproduction generates new genetic variants through recombination and affects every aspect of organismal evolution. Self-fertility and asexuality may therefore have consequences for HGT as these organisms may use HGT to generate variation. Conversely, outcrossing organisms with separate males and females may be subject to HGT due to endosymbionts and parasites. This project takes a unique, innovative approach to study the relationship between HGT and reproductive mode across Phylum Nematoda and will result in the development of a conceptual framework linking reproductive mode with HGT. These findings will advance understanding of the significance and role of HGT in eukaryotic evolution. HGT-derived genes will be studied in a functional context and these results will contribute to understanding the patterns of environmental selection shaping HGT-derived genes in eukaryotic genomes. This research will result in important discoveries regarding the ways in which reproductive mode and HGT have shaped genome evolution and contribute novel insights to the broader scientific understanding of how evolutionary processes shape genomic patterns. In order to achieve these objectives this project has four specific goals: (1) Develop bioinformatic methods for separating contaminants from true HGT in de novo sequencing projects; (2) Develop a probabilistic approach for identifying HGT in assembled genome sequences; (3) Utilize phylogenetic comparative methods to analyze HGT in outcrossing, self-fertile and asexual organisms; and (4) Develop a new, innovative summer research program for undergraduates, Computational Research Experience at the University of Alabama (CRE@UA).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.