核苷酸序列的模拟

1、1核苷酸序列的模擬楊義清於國家理論科學中心南區2生物物理n傳統的定義是以X-ray跟NMR來決定蛋白質結構等的問題。n用物理的方法來解決生物系統中的問題， 特別是以理論物理的方法。n我感興趣的研究領域：核苷酸序列中各類特殊序列的成因。3The Nobel Prize in Physiology or Medicine 1962Maurice H.F. WilkinsFrancis H. C. CrickJames D. Watson 4DNA結構5Coding region6Codon Table7microsatellite DNAn指單一核苷酸序列樣式所組成的序列，從頭到尾都是由連續的序列

2、樣式所組成，中間沒有被其他鹼基打斷，所有的序列樣式均介於26個鹼基之間。尚有SSRs simple sequences repeats 和STRs short tandem repeats等這些代表連續重複序列的名稱。8Why interest in SSRs?nImportant role in genetic disease, genome organization, and evolutionary processesnthe most widely used markers for genetic mapping, evolution studies and forensic fing

3、erprinting.nthe length polymorphism of microsatelliters is frequently used in medical purpose. 9Medical Purposesngenetic mechanism of molecular event for evolution and progression of tumor.nsuch as endometrial carcinoma (Gurin et.al., 1999), hereditary nonpolyosis colorectal carcinoma (Eshleman &

4、; Markowitz, 1996), thyroid tumor (Lazzereschi et.al., 1994), gastric cancer (Rhyu et.al., 1994), pancreatic cancer (Han et.al., 1993), and bladder tumor (Orlow et.al., 1994).1011有關SSRs成因機制的研究nThe results of many researchers favor the model of polymerase template slippage (Henderson et.al.,1992; Mor

5、ral et.al., 1991; Freudenreich et.al., 1997; Parker & Marinus, 1992)nOhta and Kimura (1973) introduced the stepwise mutation model with the polymerase template slippage, and the microsatellite length follows a simple random walk with a reflecting barrier at one repeat unit.12nA continuous-time M

6、arkov chain model that incorporates slippage events and point mutations, a stationary was resulted (Kruglyak et.al., 1998; 1999)nDokholyan et.al. (1997; 1998) analyed a simplified model of unequal chromosomal crossing over for expressing the power-law distributionNonlinear model13Han跟Li的研究cond-mat/202525914small worldD.J. Watts and S.H. Strogatz, Nature 393, 440-442 (1998)15分析上所得到的結果nSSR的長度分佈不是指數，也非對數nSSR分布具有高度相關性(非隨機分布)n這種影響已經不是slippage與point mutation能夠形成的n進一步的想法是提出一個機制來模擬，但是要具有生物上的證據What is this