影响链球菌属肺炎球菌基因组密码子使用的因素分析

Analysis of Factors Shaping S.pneumoniae Codon Usage

链球菌属肺炎球菌 (Streptococcuspneumoniae)的完整基因组序列已经测定完毕并于近期发表。对肺炎球菌基因组序列进行了详细分析 ,研究了基因组密码子的使用模式和影响密码子使用的因素。高水平表达基因的密码子第三位碱基使用胞嘧啶 (C)的频率比表达水平低的基因使用C有显著的提高 ,表达水平较低的基因在密码子的第三位碱基更趋向使用鸟嘌呤 (G)。基因的表达水平与对应分析的第一条向量轴呈显著相关 (R =0 .86 )。比较表达水平高、低的两组基因的密码子使用模式发现 ,基因的表达水平对于密码子使用有显著的影响。基因碱基G +C的组成与基因的表达水平 (R =0 .4 4 )、对应分析的第一条向量轴 (R =0 .5 1)有显著的相关 ,对基因的表达水平、密码子的使用有显著的影响。通过GC skew、蛋白质的疏水性、基因的长度分析 ,发现不同长度的基因表达水平、GC含量、GC3s有差异。结果表明 ,在表达水平上的自然选择以及基因的碱基组成是影响肺炎球菌基因密码子使用的主要因素 。

Streptococcus pneumoniae is a Gram positive bacteria causing community acquired pneumonia,bacteremia,meningitis and otitis media. As a human pathogen, S.pneumoniae is the most common bacterial cause of acute respiratory infection and otitis media and is estimated to result in over 3 million deaths in children every year worldwide. S. pneumoniae has played a pivotal role in the fields of genetics and microbiology. The complete genome of S. pneumoniae was sequenced and published recently. In order to have a further insight into the synonymous codon usage evolution and to study S. pneumoniae gene codon usage pattern in highly and lowly expressed genes,factors shaping synonymous codon usage pattern of S. pneumoniae were analyzed in this paper. Genes larger than of equal to 300bp of the complete genome of S.pneumoniae (1709 genes in total) were analyzed. The gene expression level(CAI,codon adaption index),RSCU(relative synonymous codon usage),Nc(effective codon numbers),A3s,T3s,G3s,C3s(the frequencies of the adenine,thymine,guanine and cytosine at the synonymous third position of codons,respectively),GC (frequency of guanine+cytosine in gene sequence),GC3s (frequency of guanine+cytosine at the synonymous third position of codons) values and multivariate statistics were calculated. The results show that there is a significant increment of cytosine(C) usage at the synonymous positions in highly expressed genes than lowly expressed genes,while lowly expressed genes tend to use guanine (G) at synonymous sites. Gene expression has a significant correlation with the first axis of correspondence analysis (COA; R =0.86) and significant effects on codon usage by comparing the codon usage patterns of highly expressed genes and lowly expressed genes. The G+C content of genes has a moderately correlation with gene expression( R =0.44) and the first axis of the COA ( R =0.51),and therefore shapes gene expression and codon usage in S.pneumoniae . The dataset is divided into 6 groups by gene length. Then,gene expression level,GC3s and Nc values are compared among 6 different gene length groups(>=300bp,2000～2999bp,1500～1999bp,1000～1499bp,500～999bp,<500bp). CAI,GC3s and Nc values show some differences among different gene length groups. Protein hydrophobicities do not show significant influence on codon usage pattern. In summary,the natural selection on gene expression level and the base composition of genes are the major factors affecting codon usage of S.pneumoniae . Gene length shapes codon usage of S. pneumoniae in a minor way.