PDF(Pubmed)
Abstract：
The Neolithic transition introduced major diet and lifestyle changes to human populations across continents. Beyond well-documented bioarcheological and genetic effects, whether these changes also had molecular-level epigenetic repercussions in past human populations has been an open question. In fact, methylation signatures can be inferred from UDG-treated ancient DNA through postmortem damage patterns, but with low signal-to-noise ratios; it is thus unclear whether published paleogenomes would provide the necessary resolution to discover systematic effects of lifestyle and diet shifts. To address this we compiled UDG-treated shotgun genomes of 13 pre-Neolithic hunter-gatherers (HGs) and 21 Neolithic farmers (NFs) individuals from West and North Eurasia, published by six different laboratories and with coverage c.1×-58× (median = 9×). We used epiPALEOMIX and a Monte Carlo normalization scheme to estimate methylation levels per genome. Our paleomethylome dataset showed expected genome-wide methylation patterns such as CpG island hypomethylation. However, analyzing the data using various approaches did not yield any systematic signals for subsistence type, genetic sex, or tissue effects. Comparing the HG-NF methylation differences in our dataset with methylation differences between hunter-gatherers versus farmers in modern-day Central Africa also did not yield consistent results. Meanwhile, paleomethylome profiles did cluster strongly by their laboratories of origin. Using larger data volumes, minimizing technical noise and/or using alternative protocols may be necessary for capturing subtle environment-related biological signals from paleomethylomes.
摘要：
新石器时代的转变给各大洲的人类带来了重大的饮食和生活方式的改变。除了有据可查的生物考古和遗传效应，这些变化是否在过去的人群中也有分子水平的表观遗传影响一直是一个悬而未决的问题.事实上,甲基化特征可以通过死后损伤模式从UDG处理的古代DNA中推断出来，但是信噪比较低;因此，尚不清楚已发表的古基因组是否会提供必要的解决方案来发现生活方式和饮食变化的系统影响。为了解决这个问题，我们编制了UDG处理的shot弹枪基因组，包括来自欧亚大陆西部和北部的13个新石器时代的狩猎采集者（HG）和21个新石器时代的农民（NFs）。由六个不同的实验室发布，覆盖率为c.1×-58×（中位数=9×）。我们使用epPALEOMIX和蒙特卡洛归一化方案来估计每个基因组的甲基化水平。我们的古甲基化组数据集显示了预期的全基因组甲基化模式，例如CpG岛甲基化。然而,使用各种方法分析数据并没有产生任何用于生活类型的系统信号，遗传性别,或组织效应。将我们数据集中的HG-NF甲基化差异与现代中非的狩猎采集者与农民之间的甲基化差异进行比较也没有产生一致的结果。同时,古甲基化体概况确实因其起源实验室而强烈聚集。使用更大的数据量，最小化技术噪声和/或使用替代方案对于从古甲基化体中捕获细微的环境相关生物信号可能是必要的。
