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Functional and evolutionary implications of in silico gene deletionsJacobs, Christopher 12 February 2016 (has links)
Understanding how genetic modifications, individual or in combination, affect organismal fitness or other phenotypes is a challenge common to several areas of biology, including human health & genetics, metabolic engineering, and evolutionary biology. The importance of a gene can be quantified by measuring the phenotypic impact of its associated genetic perturbations "here and now", e.g. the growth rate of a mutant microbe. However, each gene also maintains a historical record of its cumulative importance maintained throughout millions of years of natural selection in the form of its degree of sequence conservation along phylogenetic branches. This thesis focuses on whether and how the phenotypic and evolutionary importance of genes are related to each other.
Towards this goal, I developed a new approach for characterizing the phenotypic consequences of genetic modifications in genome-scale biochemical networks using constraint-based computational models of metabolism. In particular, I investigated the impact of gene loss events on fitness in the model organism Saccharomyces cerevisiae, and found that my new metric for estimating the cost of gene deletion correlates with gene evolutionary rate. I found that previous failures to uncover this correlation using similar techniques may have been the result of an incorrect assumption about how isoenzymes deletions affect the reaction they catalyze.
I next hypothesized that the improvement my metric showed in predicting the cost of isoenzyme loss could translate into an improved capacity to predict the impact of pairs of gene deletions involving isoenzymes. Studies of such pair-wise genetic perturbations are important, because the extent to which a genetic perturbation modifies any given phenotype is often dependent on the genetic background upon which it has been performed. This lack of independence within sets of perturbations is termed epistasis. My results showed that, indeed, the new metric displays an increased capacity to predict epistatic interactions between pairs of genes.
In addition to shedding light on the relationship between the functional and evolutionary importance of genes, further developments of our approach may lead to better prediction of gene knockout phenotypes, with applications ranging from metabolic engineering to the search for gene targets for therapeutic applications.
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工作情境、能力高低、與不同激勵策略對工作表現的影響 / Effects of work situation, ability, and different motivation strategies on task performance: A study of social compensation phenomenon黃國倫, Huang, Kuo-Lun Unknown Date (has links)
早期有許多實證研究均發現,個人在團體中的表現,反而不若只有個人獨自一人時的的表現,除了可能有因在團體中彼此協調不足所造成的損失外, Latan'e 等學者 (1979) 更進一步指出,這還有可能是因為當處在團體中時,由於責任分散了而形成混水摸魚的現象,並稱之為「社會閒散」 (social loafing) ,這是一種動機性的損失。
不過,在某些情況下,我們也可能在團體中的表現反而比個人自己一人時更好, Williams 與Karau (1991) 稱此相對於社會閒散的現象為「社會補償」 (social compensation) ,例如,當團體的工作對我們而言是有意義的或重要的,又知覺到團體其他成員的能力較弱時,我們便可能會付出較多的努力工作,以補償同伴能力之不足。本研究之主要目的,即在探討最可能產生社會補償現象的情況。
然而,由於人類行為的複雜性,影響個人是否表現社會補償的因素或許甚多,但本研究者假設,最主要的因素還是在於強化個人主觀覺知的「輸入與輸出的連結強度」以及「不可或缺性」。所以在本研究中,研究者將工作類型限定在不連續性工作上,而操弄工作情境、個人能力高低以及獎懲制度等三個獨變項,而在控制其他變項的情況下,探討獨變項對於引發社會補償現象的影響。因此,本研究實際上為一2×2×2 的三因子受試者間設計。
本研究採實驗室實驗法操弄獨變項,實驗中所要進行的工作為綁提圈作業,研究者藉由指導語的說明及假回饋來操弄175 位大學生對於「輸入與輸出連結強度」及「不可或缺性」的知覺。研究結果顯示,工作情境與個人能力高低在工作表現、知覺到的不可或缺性強度、知覺到的輸入與輸出連結強度、以及個人與他人努力程度差異之預期等方面有交互作用存在,顯示當個人能力高時,團體組受試者比個人組受試者知覺到較高的不可或缺性,而輸入與輸出之連結強度亦變得較緊密;而當個人能力低時,團體組受試者則反而比個人組受試者知覺到較低的不可或缺性,及較弱的輸入與輸出連結強度。
此外,知覺到的不可或缺性程度與工作表現有正相關存在,不可或缺性愈高,工作表現也有愈佳的趨勢,而由工作情境與能力高低在工作表現上的交互作用看來,團體╱高能力組受試者的工作表現高於個人╱高能力組,而團體╱低能力組則低於個人╱低能力組,表示在不可或缺性高的情況下,受試者最有可能產生社會補償行為。而在本研究中也發現,能力高低的操弄亦會造成個人工作表現、知覺到的不可或缺性與負向情緒反應的不同,低能力者的工作表現反而優於高能力者,且在工作過程中會產生較強烈的負向情緒。而接受懲罰操弄的組別,受試者也有較強的控制感及負向情緒。研究者最後並以徑路分析整合前述各項證據,大致支持原先的理論建構。
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