Zheng Chunfang, Zhu Qian, Adam Zaky, Sankoff David
Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
Bioinformatics. 2008 Jul 1;24(13):i96-104. doi: 10.1093/bioinformatics/btn146.
Some present day species have incurred a whole genome doubling event in their evolutionary history, and this is reflected today in patterns of duplicated segments scattered throughout their chromosomes. These duplications may be used as data to 'halve' the genome, i.e. to reconstruct the ancestral genome at the moment of doubling, but the solution is often highly nonunique. To resolve this problem, we take account of outgroups, external reference genomes, to guide and narrow down the search.
We improve on a previous, computationally costly, 'brute force' method by adapting the genome halving algorithm of El-Mabrouk and Sankoff so that it rapidly and accurately constructs an ancestor close the outgroups, prior to a local optimization heuristic. We apply this to reconstruct the predoubling ancestor of Saccharomyces cerevisiae and Candida glabrata, guided by the genomes of three other yeasts that diverged before the genome doubling event. We analyze the results in terms (1) of the minimum evolution criterion, (2) how close the genome halving result is to the final (local) minimum and (3) how close the final result is to an ancestor manually constructed by an expert with access to additional information. We also visualize the set of reconstructed ancestors using classic multidimensional scaling to see what aspects of the two doubled and three unduplicated genomes influence the differences among the reconstructions.
The experimental software is available on request.
一些现代物种在其进化历史中经历了全基因组加倍事件,这在如今散布于其染色体中的重复片段模式中得以体现。这些重复片段可作为数据来“减半”基因组,即重建加倍时刻的祖先基因组,但解决方案往往高度不唯一。为解决此问题,我们考虑外类群,即外部参考基因组,以指导并缩小搜索范围。
我们改进了之前计算成本高昂的“暴力”方法,通过调整埃尔 - 马布鲁克(El - Mabrouk)和桑科夫(Sankoff)的基因组减半算法,使其在局部优化启发式算法之前,能快速且准确地构建一个接近外类群的祖先。我们将此应用于重建酿酒酵母(Saccharomyces cerevisiae)和光滑念珠菌(Candida glabrata)的加倍前祖先,并以在基因组加倍事件之前分化的其他三种酵母的基因组为指导。我们从以下几个方面分析结果:(1)最小进化标准;(2)基因组减半结果与最终(局部)最小值的接近程度;(3)最终结果与由能够获取额外信息的专家手动构建的祖先的接近程度。我们还使用经典多维缩放对重建的祖先集进行可视化,以查看两个加倍基因组和三个未加倍基因组的哪些方面影响了重建结果之间的差异。
可根据请求提供实验软件。