Department of Biological Sciences, University of Arkansas, Fayetteville, AR, USA.
Department of Ecology and Evolutionary Biology, University of Tennessee, Knoxville, TN, USA.
Mol Biol Evol. 2021 Apr 13;38(4):1641-1652. doi: 10.1093/molbev/msaa318.
Ultraconserved elements (UCEs) are stretches of hundreds of nucleotides with highly conserved cores flanked by variable regions. Although the selective forces responsible for the preservation of UCEs are unknown, they are nonetheless believed to contain phylogenetically meaningful information from deep to shallow divergence events. Phylogenetic applications of UCEs assume the same degree of rate heterogeneity applies across the entire locus, including variable flanking regions. We present a Wright-Fisher model of selection on nucleotides (SelON) which includes the effects of mutation, drift, and spatially varying, stabilizing selection for an optimal nucleotide sequence. The SelON model assumes the strength of stabilizing selection follows a position-dependent Gaussian function whose exact shape can vary between UCEs. We evaluate SelON by comparing its performance to a simpler and spatially invariant GTR+Γ model using an empirical data set of 400 vertebrate UCEs used to determine the phylogenetic position of turtles. We observe much improvement in model fit of SelON over the GTR+Γ model, and support for turtles as sister to lepidosaurs. Overall, the UCE-specific parameters SelON estimates provide a compact way of quantifying the strength and variation in selection within and across UCEs. SelON can also be extended to include more realistic mapping functions between sequence and stabilizing selection as well as allow for greater levels of rate heterogeneity. By more explicitly modeling the nature of selection on UCEs, SelON and similar approaches can be used to better understand the biological mechanisms responsible for their preservation across highly divergent taxa and long evolutionary time scales.
超保守元件 (UCEs) 是由高度保守的核心侧翼可变区组成的数百个核苷酸的延伸。虽然负责保存 UCEs 的选择压力尚不清楚，但人们仍然相信它们包含了从深到浅的分歧事件中具有系统发育意义的信息。UCEs 的系统发育应用假设整个基因座（包括可变侧翼区）的核苷酸的异速选择程度相同。我们提出了一个核苷酸选择的 Wright-Fisher 模型 (SelON)，该模型包括突变、漂变和空间变化的稳定选择对最优核苷酸序列的影响。SelON 模型假设稳定选择的强度遵循位置相关的高斯函数，其具体形状可以在 UCEs 之间变化。我们通过比较其性能与更简单的空间不变 GTR+Γ模型来评估 SelON，该模型使用了 400 个脊椎动物 UCEs 的经验数据集来确定海龟的系统发育位置。我们观察到 SelON 对 GTR+Γ 模型的拟合度有了很大的提高，并支持海龟与鳞龙类是姐妹关系。总的来说，SelON 估计的 UCE 特异性参数提供了一种量化 UCE 内和跨 UCE 选择强度和变异的紧凑方法。SelON 还可以扩展到包括序列和稳定选择之间更现实的映射函数，并允许更大程度的异速选择。通过更明确地模拟 UCEs 上选择的性质，SelON 和类似的方法可以用于更好地理解它们在高度分化的分类群和长期进化时间尺度上保存的生物学机制。
