黑腹果蠅管家基因之研究-以生物特性及分子演化之觀點

Study on Housekeeping Genes in Drosophila melanogaster-Based on Biological Characteristics and Molecular Evolution

盧怡文(Yi-Wen Lu)

指導教授 ： 丘臺生

共同指導教授 ： 林仲彥

國立臺灣大學/生命科學院/生命科學系/博士(2018年)

https://doi.org/10.6342/NTU201801917

摘要

管家基因是維持細胞基礎功能及細胞存活的重要基因，因為管家基因在生物體的重要性，故本論文採用昆蟲的模式生物-黑腹果蠅來進行管家基因之相關研究。本論文的研究目標為: 1)研究黑腹果蠅管家基因的生物特性， 2) 研究影響黑腹果蠅管家基因演化速率的可能因子，以及 3) 研究影響黑腹果蠅管家基因密碼子使用偏性的可能因子。本論文使用生物資訊的方法，對黑腹果蠅1,107個管家基因及1,084 個高組織特異性基因來進行相關分析,在比較分析這兩群基因的各種生物特性時，發現這兩群基因存在很大的差別，管家基因的演化速率比高組織特異性基因要慢，表示管家基因在演化較為保守。進一步分析可能影響管家基因的演化速率的因子，發現可能的相關因子為：密碼子使用偏性、基因表現量、世系年齡、蛋白質交互作用的情形、蛋白質作用部位的占比、以及蛋白質的多功性，利用淨相關分析發現密碼子使用偏性是影響管家基因的演化速率最主要的可能因子。本論文再進階分析影響管家基因密碼子使用偏性的因子，分析結果發現偏性突變及轉譯篩選可能是影響管家基因密碼子使用偏性的重要因子，而蛋白質交互作用的情形以及蛋白質作用部位的占比同樣為影響管家基因密碼子使用偏性的可能因子。本論文探討昆蟲模式生物-黑腹果蠅其管家基因的生物特性及分子演化的研究結果，期能作為未來生醫及農業相關應用研究之基礎。

關鍵字

管家基因 ； 組織特異性 ； 生物特性 ； 演化速率 ； 密碼子使用偏性

並列摘要

Housekeeping genes (HK genes) are required for cell survival and the maintenance of basic cellular functions. This thesis focused on the research of HK genes in Drosophila melanogaster. The aims of this thesis were: 1) investigation of biological characteristics in HK genes, 2) investigation of factors affecting evolution rates in HK genes, 3) investigation of factors affecting codon usage patterns in HK genes. In this thesis, bioinformatics approaches were employed to analyze 1,107 HK genes and 1,084 high tissue specificity genes (HTS genes) of D. melanogaster. The comparisons of multiple biological characteristics between these two gene groups suggested that these characteristics were significantly different between these two groups. The average evolutionary rate of HK genes is slower than that of HTS genes. To identify the possible factors that constrain the evolutionary rates of HK genes, several factors were analyzed herein. Codon usage bias (CUB), gene expression level, phyletic age, protein connectivity, proportion of protein interacting length and protein multifunctionality were found to be related to the influence on evolutionary rates of HK genes. Partial correlation analysis revealed that CUB has the strongest influence than other factors on influencing the evolutionary rate variation between these two gene groups. Therefore, further analyses were made to identify the factors that potentially influence the CUB of HK genes. The results suggested that mutation pressure and natural selection highly correlate with CUB in the HK genes and two topological properties of HK proteins (proportion of protein interacting length and protein connectivity) also correlate with CUB in the HK genes. The results provide more insight into biological characteristics and the molecular evolution in the HK genes of D. melanogaster, and the results may support future investigations of potential applications in agricultural and biomedical field.

並列關鍵字

housekeeping gene ； tissue specificity ； evolutionary rate ； codon usage bias ； biological properties

參考文獻

1. Butte AJ, Dzau VJ, Glueck SB: Further defining housekeeping, or "maintenance," genes focus on "a compendium of gene expression in normal human tissues". Physiological genomics (2001) 7(2):95-96. doi: 10.1152/ physiolgenomics.2001.7.2.95.

2. Kadota K, Nishimura S, Bono H, Nakamura S, Hayashizaki Y, Okazaki Y, Takahashi K: Detection of genes with tissue-specific expression patterns using akaike's information criterion procedure. Physiological genomics (2003) 12(3):251-259. doi: 10.1152/physiolgenomics.00153.2002.

3. Dezso Z, Nikolsky Y, Sviridov E, Shi W, Serebriyskaya T, Dosymbekov D, Bugrim A, Rakhmatulin E, Brennan RJ, Guryanov A, Li K, Blake J, Samaha RR, Nikolskaya T: A comprehensive functional analysis of tissue specificity of human gene expression. BMC biology (2008) 6(49. doi: 10.1186/ 1741-7007-6-49.

4. Duret L: Evolution of synonymous codon usage in metazoans. Current opinion in genetics & development (2002) 12(6):640-649.

5. Grantham R, Gautier C, Gouy M, Mercier R, Pave A: Codon catalog usage and the genome hypothesis. Nucleic acids research (1980) 8(1):r49-r62.