Mapping deep evolutionary divergences in cellular models of stress response

绘制应激反应细胞模型的深层进化差异

• 批准号: 10699808
• 负责人: Rachel Beth Brem
• 金额: $ 8.78万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699808
• 关键词: Biological Models; Biomedical Research; Biophysical Process; Cell Aging; Cell model; Cells; Chromosome Mapping; Data Analyses; Development; Development Plans; Dissection; Distant; Doctor of Philosophy; Evolution; Family; Funding; Genes; Genetic; Genomics; Goals; Growth; High temperature of physical object; Individual; Kluyveromyces; Maps; Methods; Mexican; Microbiology; Modeling; Molecular Biology; Molecular Evolution; Mus; Nature; Parents; Phenotype; Quantitative Genetics; Resistance; Rest; Saccharomyces; Saccharomycetales; Scientist; Stress; Syndrome; Testing; Training; Variant; Work; Yeasts; biological adaptation to stress; career; college; doctoral student; interest; programs; reproductive; skills; statistics; training opportunity; trait

SUMMARY Understanding how nature builds new traits is a fundamental goal of evolutionary genetics. Unbiased experimental dissection of trait variation from the wild has to date used linkage or association mapping, which are suitable only for crosses between compatible individuals of a given species. The parent R01 for this supplement makes use of a method from our group called RH-seq, which enables the genetic mapping of natural trait variation between reproductively isolated species. One aim of the parent R01 focuses on evolutionary and biophysical mechanisms of a model trait, high-temperature growth in Saccharomyces yeast. A second aim of the parent R01 applies RH-seq to a cell-autonomous mouse phenotype called cellular senescence. In this supplement, we propose to provide training to Abel Duarte, a Ph.D. student in the Microbiology graduate program at UC Berkeley, to extend our analyses to the budding yeast Kluyveromyces. In these distant relatives of Saccharomyces, we have found a suite of stress-resistance traits distinguishing one species, K. marxianus, from the rest of the clade. We propose to use RH-seq and other omics approaches to dissect this trait syndrome. Since K. marxianus diverged 20 million years ago from its closest relative, the clade affords us the opportunity to study trait evolution over a far deeper divergence than we or others have achieved in any quantitative-genetic mapping work to date. This project will involve computational data analysis, applied statistics, and molecular evolution tests as well as experimental genomics and molecular biology. It represents an excellent training opportunity for Abel to master computational/quantitative skills, which he has set out in his Individual Development Plan as a major training goal. As such, funding this supplement will support Abel’s development as a quantitative genomic scientist; and since Abel is of Mexican descent and the first in his family to have gone to college, as he harnesses our training to complete his Ph.D. and move on to a career in biomedical research, he will contribute to the diversity of the workforce.

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