CAREER: Determining the impact of asexual ploidy transitions on evolutionary trajectories

这项研究将确定改变细胞内基因拷贝数的能力如何影响进化。遗传变异对于物种能够生存并适应不断变化的环境非常重要。对于大多数动植物来说，交配创造了新的基因组合，产生了变异。然而，对于许多真菌来说，交配是罕见的或不存在的。相反，在生长过程中，真菌经常改变它们所包含的染色体的数量和染色体集(倍性)。这项研究使用白色念珠菌，一种人类的真菌病原体，来确定倍性变化的频率，以及包括抗真菌药物在内的哪些环境促进这些变化。一个结果将是更好地理解毒力和耐药性的演变。该项目将开发一个以白念珠菌倍性变异为引人注目的生物学背景的高级写作密集型课堂；该课程将旨在教会学生如何将实验结果从数据转化为知识，同时挑战学生将科学知识提炼成公众可以接触到的框架。这些数据将在一个入门生物实验室模块中生成，该模块测量具有不同倍性状态的白色念珠菌菌株的突变率。虽然无性倍性转变在许多真菌物种和不同的生长环境中都有很好的记录，但它们是驱动进化过程还是仅仅是基因组不稳定性升高的结果仍有待明确测试。倍性变化的环境信号和途径还没有得到很好的描述，无性倍性转变的后果也没有在进化框架内得到测试。通过在中短时间尺度上筛选许多体外和寄主环境中念珠菌基因组大小的变化，将识别促进倍性转变的环境。通过构建在基因上锁定在二倍体或多倍体状态的白色念珠菌菌株，研究人员将通过比较毒力和抗真菌药物耐药性选择的比率和结果，测试倍体转变如何有助于进化过程。这一奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The research will determine how the ability to change the number of copies of genes within a cell affects evolution. Genetic variation is important for species to be able to survive and adapt to changing environments. For most plants and animals, mating creates new combinations of genes, generating variation. However for many fungi, mating is rare or absent. Instead, during growth fungi often change the number of chromosomes and chromosome sets (ploidy) they contain. This research uses Candida albicans, a fungal pathogen of humans, to identify how frequently changes in ploidy occur, and what environments promote these changes, including antifungal drugs. One result will be a better understanding of the evolution of virulence and drug resistance. The project will develop an upper-division writing-intensive class using C. albicans ploidy variation as a compelling biological context; the course will be designed to teach students how to transform experimental results from data to knowledge while challenging students to distill scientific knowledge into a framework accessible to the general public. The data will be generated in an introductory biology lab module that measures mutation rates in C. albicans strains with different ploidy states. While asexual ploidy transitions are well-documented to occur in many fungal species and across diverse growth environments, whether they drive evolutionary processes or are simply a consequence of elevated genome instability remains to be explicitly tested. The environmental signals and pathways to ploidy changes have not been well characterized, nor have the consequences of asexual ploidy transitions been tested within an evolutionary framework. By screening for Candida genome size changes across many in vitro and host environments at short- and mid-length time scales, environments that promote ploidy transitions will be identified. By constructing C. albicans strains that are genetically-locked into the diploid or polyploid state, the researchers will test how ploidy transitions contribute to evolutionary processes by comparing the rates and outcomes of selection for virulence and antifungal drug resistance.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.