摘要
随着大规模测序技术的不断发展,基因组测序工作在速度变得越来越快的同时,其价格也越来越廉价,已经引领生命科学进入以基因组学为代表的“组学”时代。然而,以基因组为代表的“组学”数据具有数据量大和数据关系复杂等特点,尤其是基因组分析的研究对象从之前对几个基因的普通生物学研究已经转变为对基因组中成千上万个基因的分析工作。为了更快、更全面地分析和研究以基因组为代表的“组学”数据,生物信息学作为一门新的交叉学科领域已应运而生,它主要是综合使用计算机科学与技术以及统计科学和其它相关学科来解决大规模生物学数据处理的一门学科。
本文主要目的是在大熊猫基因组和日本血吸虫基因组数据的分析工作中应用生物信息学方法,研究大熊猫独特饮食习性和日本血吸虫在动物界中的系统发育关系以及特殊生物学性状等复杂生物学问题。首先,在大熊猫基因组分析中,我们针对大熊猫吃竹子不吃肉的问题在进行了较为深入的研究。我们发现大熊猫多巴胺(dopamine)、降肾上腺素(norepinephrine)和肾上腺素(epinephrine)等通路上的关键酶COMT在蛋白三维结构上和小RNA调控上与人类相比已发生了显著的变化,这极可能引起大熊猫饮食习性的改变。研究结果表明,大熊猫饮食习性的改变是一个极为复杂的问题,绝不仅仅是由于其某个味觉基因变成假基因或其肠道微生物的作用所引起的,而可能还与其大脑中关键基因(如COMT)或通路发生功能改变有关。即使我们考虑多巴胺和降肾上腺素等通路的变异,也不一定能完全解释大熊猫吃竹子不吃肉这个及其复杂的问题,但本研究中生物信息学分析角度提供一条崭新的思路。
在日本血吸虫基因组的分析中,我们采用分子进化模型和最大似然方法构建了一个包含动物界中17个物种和103,009个氨基酸的基因组系统发育树和一个包含54个物种和6,412个核酸的基因系统发育树。我们的研究结果表明,日本血吸虫位于冠轮动物(Lophotrochozoa)中的扁形动物(Platyhelminthes)。我们还研究了日本血吸虫与其宿主人的基因水平转移(HGT)等复杂生物学问题。通过进化基因组和比较基因组的方法,我们尚未发现比较强的证据可以显示出人和日本血吸虫之间存在基因水平转移的现象。当然,这极有可能是由于我们迄今只分析了日本血吸虫中的6,000多个基因,还有将近8,000个基因没有分析的缘故。
此外,本研究还建立了相关生物信息系统(PBmice和Apanda等),这些系统的建立一方面为我们的实际研究提供了数据基础,另一方面促进了生物信息学自身的发展。总之,我们认为,大熊猫基因组和日本血吸虫基因组以至于有关其它生物基因组的更多的生物问题,可以通过生物信息学方法来加以深入研究,并最终给予合理的解释。
引文
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