The Role of Phylogenetically Conserved Elements in Shaping Patterns of Human Genomic Diversity.
The Role of Phylogenetically Conserved Elements in Shaping Patterns of Human Genomic Diversity.
复制标题
系统发育保守元素在塑造人类基因组多样性模式中的作用。
DOI：
10.1093/molbev/msy145
复制
发表时间：
2018
影响因子：
10.7
通讯作者：
Hammer,MichaelF
中科院分区：
文献类型：
--
作者：
Woerner,AugustE;Veeramah,KrishnaR;Watkins,JosephC;Hammer,MichaelF
进化遗传学研究表明，核苷酸多样性水平与重组率或与基因的遗传距离呈正相关。正向选择和净化选择分别通过遗传搭便车和背景选择作为这些相关性的来源。系统发育保守元件（CEs）很短（约100 bp），分布广泛（约占基因组的5%），通常在远离基因的地方发现。虽然许多ce的功能尚不清楚，但ce也与连锁位点的多样性减少有关。利用来自约鲁巴人（Yoruba）和CEU两个人类种群的高覆盖率（bbb80 ×）全基因组数据，我们对多样性、重组率和基因连锁进行了精细的评估。我们发现，与基因连锁相比，本地重组率对多样性水平的影响更大，而且这些重组效应即使在远离基因的区域也会持续存在。我们的全基因组模型表明，与重组或gc偏向基因转换相比，在ce内或与ce相关的位点上的选择更好地解释了所观察到的基因组多样性模式。一个主要的暗示是，人类基因组中很少有位点被预测不受选择的影响。这些位点，我们称之为人类的“中性染色体”，仅占常染色体的1.2%和X染色体的5.1%。中性染色体的人口统计学分析表明，与以前的分析推断相比，祖先人类种群的人口规模更大，增长率更低。
Evolutionary genetic studies have shown a positive correlation between levels of nucleotide diversity and either rates of recombination or genetic distance to genes. Both positive-directional and purifying selection have been offered as the source of these correlations via genetic hitchhiking and background selection, respectively. Phylogenetically conserved elements (CEs) are short (∼100 bp), widely distributed (comprising ∼5% of genome), sequences that are often found far from genes. While the function of many CEs is unknown, CEs also are associated with reduced diversity at linked sites. Using high coverage (>80×) whole genome data from two human populations, the Yoruba and the CEU, we perform fine scale evaluations of diversity, rates of recombination, and linkage to genes. We find that the local rate of recombination has a stronger effect on levels of diversity than linkage to genes, and that these effects of recombination persist even in regions far from genes. Our whole genome modeling demonstrates that, rather than recombination or GC-biased gene conversion, selection on sites within or linked to CEs better explains the observed genomic diversity patterns. A major implication is that very few sites in the human genome are predicted to be free of the effects of selection. These sites, which we refer to as the human “neutralome,” comprise only 1.2% of the autosomes and 5.1% of the X chromosome. Demographic analysis of the neutralome reveals larger population sizes and lower rates of growth for ancestral human populations than inferred by previous analyses.