南加州大学Jazlyn A. Mooney课题组的一项最新研究提出了参考基因组的选择损害了群体遗传分析。这一研究成果于2025年9月22日发表在国际顶尖学术期刊《细胞》上。

通过将灰狐（Urocyon cinereogentethem）的全基因组序列数据映射到同种参考和两个异种犬科动物基因组（狗和北极狐），小组证明了参考偏差显著影响种群基因组分析。对同种基因组的定位使读取配对提高了约5%，检测到的SNPs多26%-32%，单基因多33%-35%。核苷酸多样性估计值提高了30%以上，FST从0.189提高到0.197，有效种群大小估计值比同种参考高出30% - 60%。异种参考染色体末端的重组率变化可达3倍。重要的是，FST异常值检测明显不同，异源基因组鉴定出的独特异常窗口数是其两倍。这些发现突出了参考基因组选择的影响以及同种基因组研究对准确进化推断的重要性。

研究人员表示，描述自然种群的遗传变异对进化生物学至关重要；然而，许多非模式物种缺乏基因组资源。

附：英文原文

Title: Reference genome choice compromises population genetic analyses

Author: Maria Akopyan, Matthew Genchev, Ellie E. Armstrong, Jazlyn A. Mooney

Issue&Volume: 2025-09-22

Abstract: Characterizing genetic variation in natural populations is vital to evolutionary biology; however, many non-model species lack genomic resources. Here, we demonstrate that reference bias significantly affects population genomic analyses by mapping whole-genome sequence data from gray foxes (Urocyon cinereoargenteus) to a conspecific reference and two heterospecific canid genomes (dog and Arctic fox). Mapping to the conspecific genome improved read pairing by ～5% and detected 26%–32% more SNPs and 33%–35% more singletons. Nucleotide diversity estimates increased by over 30%, FST increased from 0.189 to 0.197, and effective population size estimates were 30%–60% higher with the conspecific reference. Recombination rates varied by up to 3-fold at chromosome ends with heterospecific references. Importantly, FST outlier detection differed markedly, with heterospecific genomes identifying twice as many unique outlier windows. These findings highlight the impact of reference genome choice and the importance of conspecific genomic resources for accurate evolutionary inference.

DOI: 10.1016/j.cell.2025.08.034

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01026-8