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

这个项目试图确定最近从一个基因中产生的多个基因如何在该基因的其他副本存在的情况下建立其功能。地球上几乎所有生物体的所有基因都来自以前存在的基因，而不是缺乏功能的DNA。随着这一过程的重复，一大组高度相似的基因可以形成一个基因家族，这往往会给有机体适应其特定生活方式带来一定的优势。例如，酿造中使用的酵母扩大了发酵的基因家族，人类扩大了能够区分好的和坏的食物的基因。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，它已经从1个拷贝扩大到14个拷贝，是测试基因家族中单个成员的功能是如何由许多遗传和功能相似的基因塑造的理想系统。该项目将生成大型数据集，并突出人们在分析方面的培训需求。因此，该项目还将通过暑期讲习班对土著学生进行生物信息学方面的培训，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的Ohno困境的概念，即当存在多个其他类似基因时功能是如何进化的。我们将使用来自白色念珠菌的TLO基因来找出每个基因如何具有单独的或与基因家族中的其他基因重叠的功能。将使用缺失基因家族中单个基因的菌株和缺少除一个外所有TLO基因的菌株来确定这些基因的分子和组织功能。缺乏单一基因的菌株将定义基因功能的重叠量，而含有单一基因的菌株将决定每个基因的功能范围。这一奖项反映了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。

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.