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。遗传变异对物种生存和适应不断变化的环境非常重要。对大多数植物和动物来说，交配会产生新的基因组合，从而产生变异。然而，对许多真菌来说，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和染色体组的数量（倍性）。这项研究使用白色念珠菌，一种人类的真菌病原体，来确定倍体发生变化的频率，以及促进这些变化的环境，包括抗真菌药物。一个结果将是更好地了解毒力和耐药性的演变。该项目将开发一个高年级写作密集型课程，使用白色念珠菌倍体变异作为令人信服的生物学背景；本课程旨在教导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一般公众可访问的框架。这些数据将在一个介绍性生物学实验室模块中生成，该模块测量不同倍体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充分的记录，但它们是否推动了进化过程，还是仅仅是基因组不稳定性升高的结果，仍有待明确测试。环境信号和倍性变化的途径尚未被很好地表征，也没有在进化框架内测试无性倍性转变的后果。通过筛选假丝酵母基因组大小在许多体外和宿主环境中短时间尺度上的变化，将确定促进倍性转变的环境。通过构建遗传锁定为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性和抗真菌药物耐药性的选择率和结果来测试倍体转变如何促进进化过程。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。

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.