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

一个生物体的DNA有两个来源：(a)从父母遗传给后代，(b)从其他生物体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开放性问题。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，但仅限于真核生物与内共生体和寄生虫。过去十年发表的研究结果表明，古代和现代的水平转移可能在真核生物中都很常见，但由于组装基因组序列中的污染问题和缺乏在整个基因组中识别HGT的适当方法，对这些科学问题的研究受到了阻碍。现在真核生物进化中关于高温高温的最重要的问题是：(a)高温高温的可能性如何取决于生物体的生态和生活史？(b)高温气候对进化的影响是什么？该项目将开发必要的方法来研究这些问题，并分发免费的软件包，使其他科学研究人员能够使用这些方法来识别HGT。50种线虫的参考基因组序列和基因注释将被制作出来，这些数据将通过WormBase和国家生物技术信息序列读取档案中心公开。该项目将整合研究和教育，通过在阿拉巴马大学的一个新的、创新的、有指导的夏季研究经历，培训计算生物学和科学研究方面的早期职业科学家。自我生育和无性行为的进化影响了物种遗传的重要方面，包括遗传变异的水平。有性生殖通过重组产生新的遗传变异，影响生物体进化的各个方面。因此，自生殖和无性行为可能对HGT产生影响，因为这些生物可能利用HGT产生变异。相反，雌雄分开的异交生物可能由于内共生体和寄生虫而受到HGT的影响。本项目采用一种独特的、创新的方法来研究线虫门HGT与生殖模式之间的关系，并将建立一个将生殖模式与HGT联系起来的概念框架。这些发现将促进对HGT在真核生物进化中的意义和作用的理解。hgt衍生基因将在功能背景下进行研究，这些结果将有助于理解真核生物基因组中形成hgt衍生基因的环境选择模式。这项研究将在生殖模式和HGT影响基因组进化的方式方面产生重要发现，并为进化过程如何影响基因组模式的更广泛的科学理解提供新的见解。为了实现这些目标，本项目有四个具体目标：(1)开发生物信息学方法，在从头测序项目中从真正的HGT中分离污染物；(2)建立基因组序列中HGT的概率鉴定方法；(3)利用系统发育比较方法分析异交、自交和无性生殖生物的HGT；(4)为本科生开发一个新的、创新的夏季研究项目，即阿拉巴马大学的计算研究体验（CRE@UA）。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.