CAREER: Paralog function following rapid gene family expansion in Candida albicans

该项目旨在确定当该基因的其他拷贝存在时，最近从单个基因产生的多个基因如何建立它们的功能。地球上每一种生物体中的几乎所有基因都来自先前存在的基因，而不是缺乏功能的DNA。随着这一过程的重复，大量高度相似的基因可以形成一个基因家族，这些基因家族通常使生物体在适应其特定生活方式方面具有某些优势。例如，用于酿造的酵母扩大了发酵的基因家族，人类扩大了能够区分好食物和腐烂食物的基因。人类真菌病原体白色念珠菌中的一个基因家族称为端粒相关（TLO）基因家族，已从1个拷贝扩展到14个拷贝，是测试基因家族单个成员的功能如何由许多遗传和功能相似基因的存在而形成的理想系统。该项目将生成大型数据集，并强调需要对人员进行分析培训。因此，该项目还将通过举办暑期讲习班，对土著学生进行生物信息学培训，以促进数据主权和土著研究能力。这个项目将开始解决大基因家族中大野困境的概念，即当存在多个其他相似基因时，功能如何进化。我们将使用来自C.白念珠菌，以找出每个基因如何保持单独或重叠的功能与其他基因的基因家族。将使用基因家族中缺失单个基因的菌株和除一个基因外缺失所有TLO基因的菌株来确定这些基因的分子和生物功能。缺乏单基因的菌株将确定基因功能的重叠量，而含有单基因的菌株将确定每个基因的功能范围。该奖项反映了NSF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。

This project seeks to determine how multiple genes that all arose recently from a single gene establish their function when other copies of that gene are present. Nearly all genes in every organism on the planet arose from previously existing genes and not from DNA that lacked function. As this process repeats, a large set of highly similar genes can form a gene family that often give an organism certain advantages in adapting to its specific lifestyle. For example, yeasts used in brewing have expanded gene families for fermentation and humans have expanded genes for being able to distinguish between good and rotten food. A gene family in the human fungal pathogen Candida albicans called the telomere-associated (TLO) gene family has expanded from 1 to 14 copies and is an ideal system to test how functions of individual members of gene families are shaped by the presence of many genetically and functionally similar genes. This project will generate large datasets and highlights the needs for people to be trained in analysis. This project will therefore also train Indigenous students in bioinformatics through a summer workshop to promote data sovereignty and Indigenous research capacity. This project will begin to address the concept of Ohno’s Dilemma in a large gene family, how function evolves when multiple other similar genes are present. We will use the TLO genes from C. albicans to find how each gene holds individual or overlapping functions with other genes in the gene family. Molecular and organismal functions will be determined for these genes using strains missing single genes of the gene family and strains lacking all TLO genes except for one. Strains lacking single genes will define the amount of overlap in gene functions, and strains containing single genes will determine the range of function for each gene.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.