Systems analysis of individual phenotypic differences based on genomic and transcriptomic data = 유전체와 전사체 데이터를 기반으로 동종내 개별 표현형 차이에 대한 시스템 차원의 분석

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An important challenge in biology is to discover a principle that determines individual phenotypic differences within species. To unravel this principle, we investigated the growth rates of diverse natural isolates as well as a large cross between two representative strains of Saccharomyces cerevisiae. We found that each strain has the acquired fitness trade-off between normal and stressful conditions. By analyzing gene expression profiles, we identified two well-conserved co-expression gene modules whose expression levels are related to the fitness trade-off. We found that the two gene modules determine the fitness advantage in normal and stressful conditions, and thereby are related to growth preference and stress resistance, respectively. Moreover, we found that the genetic variation of RAS/cAMP/PKA signaling pathway might be the potential route of regulating the fitness trade-off. Intriguingly, we found that the fitness trade-off of yeast can account for the different drug resistance of various cancer cell lines. Our experiments showed that we can reduce the drug resistance of cancer cells regardless of different genetic backgrounds, cell types, and anti-cancer drugs. Together, we suggest that the fitness trade-off between growth preference and stress resistance might be the evolutionary principle determines the distinct individual growth phenotype within species.
Advisors
Cho, Kwang Hyunresearcher조광현researcher
Description
한국과학기술원 :바이오및뇌공학과,
Publisher
한국과학기술원
Issue Date
2014
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 바이오및뇌공학과, 2014.2 ,[v, 57 p. :]

Keywords

Individual Phenotypic Differences; Fitness Trade-off; Genome-wide Analysis; Systems Biology; Cancer; Drug Resistance; 개별 표현형 차이; 적합성의 상충성; 유전체 수준의 분석; 시스템 생물학; 암; 약물 저항성

URI
http://hdl.handle.net/10203/221156
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=648795&flag=dissertation
Appears in Collection
BiS-Theses_Ph.D.(박사논문)
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