Zhang Wenping, Zhang Mingchun, Liu Hao
Key Laboratory of Research and Conservation of Biological Diversity in Minshan Mountain of National Park of Giant Pandas at Mianyang Normal University of Sichuan Province, College of Life Science, Mianyang Normal University, Mianyang 621000, China.
Forest Ecology and Conservation in the Upper Reaches of the Yangtze River Key Laboratory of Sichuan Province, College of Life Science, Mianyang Normal University, Mianyang 621000, China.
Genes (Basel). 2025 Sep 19;16(9):1115. doi: 10.3390/genes16091115.
: The mutational dynamics of microsatellites over deep evolutionary timescales are poorly understood. This study aims to elucidate the life history of trinucleotide microsatellites by tracing orthologous loci across divergent vertebrate lineages and characterizing their mutational pathways. : We developed a bioinformatic framework for identifying orthologous microsatellite loci using conserved flanking sequences. This approach was applied to three trinucleotide microsatellites located in exonic, intronic, and intergenic regions, respectively. These loci were amplified and sequenced across 126 individuals representing 64 vertebrate species, whose divergence times range from 6 to 150 million years ago (MYA). : Flanking sequences proved essential for reliable orthology assignment, while repeat motifs revealed distinct mutational pathways. Microsatellite decay occurs through two primary mechanisms: the complete loss of dominant repeats or their progressive reduction to solitary units (≤1 repeat). This degeneration process is facilitated by cryptic simple sequences (CSS), which act as genomic catalysts promoting birth-death transitions. Large intra-motif deletions were identified as the key mutational event driving contractions and eventual locus degeneration. Furthermore, mutational patterns were highly locus-specific, influenced by genomic context. : Although the study focused on only three loci, limiting broader generalizations, our findings provide mechanistic insights into microsatellite evolution. These results establish a foundation for modeling complex microsatellite life histories and highlight the role of CSS in facilitating evolutionary turnover.
在深度进化时间尺度上，微卫星的突变动态仍知之甚少。本研究旨在通过追踪不同脊椎动物谱系中的直系同源位点并表征其突变途径，阐明三核苷酸微卫星的生命史。
我们开发了一个生物信息学框架，利用保守的侧翼序列识别直系同源微卫星位点。该方法应用于分别位于外显子、内含子和基因间区域的三个三核苷酸微卫星。对代表64种脊椎动物的126个个体的这些位点进行了扩增和测序，这些脊椎动物的分化时间范围为6亿至1.5亿年前（百万年前）。
侧翼序列被证明对可靠的直系同源性分配至关重要，而重复基序揭示了不同的突变途径。微卫星衰变通过两种主要机制发生：优势重复序列的完全丧失或它们逐渐减少为单个单元（≤1个重复）。这种退化过程由隐蔽简单序列（CSS）促进，CSS作为基因组催化剂促进生死转变。大的基序内缺失被确定为驱动收缩和最终位点退化的关键突变事件。此外，突变模式具有高度的位点特异性，受基因组背景影响。
尽管该研究仅关注三个位点，限制了更广泛的概括，但我们的发现为微卫星进化提供了机制性见解。这些结果为模拟复杂的微卫星生命史奠定了基础，并突出了CSS在促进进化周转中的作用。
