Center for Comparative Genomics and Bioinformatics, Penn State University, University Park, Pennsylvania 16802, USA.
Genome Res. 2010 May;20(5):600-13. doi: 10.1101/gr.099044.109. Epub 2010 Mar 10.
The densities of transposable elements (TEs) in the human genome display substantial variation both within individual chromosomes and among chromosome types (autosomes and the two sex chromosomes). Finding an explanation for this variability has been challenging, especially in light of genome landscapes unique to the sex chromosomes. Here, using a multiple regression framework, we investigate primate Alu and L1 densities shaped by regional genome features and location on a particular chromosome type. As a result of our analysis, first, we build statistical models explaining up to 79% and 44% of variation in Alu and L1 element density, respectively. Second, we analyze sex chromosome versus autosome TE densities corrected for regional genomic effects. We discover that sex-chromosome bias in Alu and L1 distributions not only persists after accounting for these effects, but even presents differences in patterns, confirming preferential Alu integration in the male germline, yet likely integration of L1s in both male and female germlines or in early embryogenesis. Additionally, our models reveal that local base composition (measured by GC content and density of L1 target sites) and natural selection (inferred via density of most conserved elements) are significant to predicting densities of L1s. Interestingly, measurements of local double-stranded breaks (a 13-mer associated with genome instability) strongly correlate with densities of Alu elements; little evidence was found for the role of recombination-driven deletion in driving TE distributions over evolutionary time. Thus, Alu and L1 densities have been influenced by the combination of distinct local genome landscapes and the unique evolutionary dynamics of sex chromosomes.
人类基因组中转座元件 (TEs) 的密度在个体染色体内部和染色体类型（常染色体和两条性染色体）之间存在显著差异。要解释这种变异性一直具有挑战性，尤其是在考虑到性染色体特有的基因组景观时。在这里，我们使用多元回归框架研究了由区域基因组特征和特定染色体类型位置塑造的灵长类 Alu 和 L1 密度。作为我们分析的结果，首先，我们构建了统计模型，分别解释了高达 79%和 44%的 Alu 和 L1 元素密度变化。其次，我们分析了校正区域基因组效应后的性染色体与常染色体 TE 密度。我们发现，即使在考虑到这些效应后，Alu 和 L1 分布中的性染色体偏倚仍然存在，而且模式甚至存在差异，证实了 Alu 在雄性生殖系中的优先整合，但 L1 可能在雄性和雌性生殖系或早期胚胎发生中整合。此外，我们的模型还揭示了局部碱基组成（通过 GC 含量和 L1 靶位点密度来衡量）和自然选择（通过最保守元件的密度推断）对预测 L1 密度很重要。有趣的是，局部双链断裂（与基因组不稳定性相关的 13 -mer）的测量值与 Alu 元素的密度强烈相关；几乎没有证据表明重组驱动的缺失在进化时间内驱动 TE 分布。因此，Alu 和 L1 的密度受到不同的局部基因组景观和性染色体独特的进化动态的共同影响。
