Ancestral Alleles in the Human Genome Based on Population Sequencing Data

Ancestral allele information is useful for genetics studies. Previously, the identification of ancestral alleles was primarily based on sequence alignments between species. Alternative ways to identify ancestral alleles were proposed in this study based on population sequencing data. The methods described here utilized the diversity between haplotypes harboring ancestral and newly emerged alleles. Simulations showed that these methods were reliable for identifying ancestral alleles when the variants had not aged too greatly. Application to the human genome sequencing data suggested the role of indels in maintaining the GC content in the human genome. The deletion-to-insertion ratios and GC proportions were correlated depending on the sizes of insertions and deletions in the direction of increasing GC content. There were GC-biased fixations in single base-pair insertions and AT-biased fixations in single base-pair deletions in the results based on the proposed methods. In the current study, GC-biased gene conversions in nucleotide substitutions were very slight or insignificant. In the variants of several quantitative trait loci (QTLs), slight GC-biased gene conversion was observed in nucleotide substitutions. For the QTL indels, insertions were observed more often than deletions, and deletion-biased fixation was observed, providing new insights into the evolution of functional genes.

祖先等位基因信息在遗传学研究中具有重要应用价值。此前，祖先等位基因的识别主要依赖物种间的序列比对分析。本研究基于群体测序数据，提出了全新的祖先等位基因识别方法。本文所述方法利用了携带祖先等位基因与新出现等位基因的单倍型之间的多样性差异。模拟实验结果表明，当变异尚未经历过长时间演化时，本方法可可靠识别祖先等位基因。将本方法应用于人类基因组测序数据后，结果表明插入缺失变异（indels）在维持人类基因组GC含量方面发挥着关键作用。缺失与插入的比例及GC占比之间存在相关性，且该相关性随插入缺失片段的长度变化，整体呈现GC含量升高的趋势。基于本研究提出的方法得到的结果显示，单碱基插入存在GC偏好性固定现象，而单碱基缺失则存在AT偏好性固定现象。本研究中，核苷酸替换过程中的GC偏向性基因转换现象极为微弱，甚至可忽略不计。针对多个数量性状位点（quantitative trait loci, QTL）的变异分析显示，其核苷酸替换过程中存在微弱的GC偏向性基因转换现象。对于数量性状位点的插入缺失变异而言，插入事件的发生频率高于缺失，且存在缺失偏好性固定现象，该发现为功能基因的演化研究提供了全新视角。