Chen Yu-Chi, Vellnow Nikolas, Wilcox Justin J S, Javaheri Tehrani Sahar, Gossmann Toni I
Computational Systems Biology, Faculty of Biochemical and Chemical Engineering, TU Dortmund University, Dortmund, Germany.
Mol Ecol. 2025 Sep;34(18):e70061. doi: 10.1111/mec.70061. Epub 2025 Aug 7.
Sex-specific genomic differentiation is a crucial yet frequently overlooked factor in population genetics. In this opinion piece, we leverage the substantial genomic resources available for the great tit (Parus major), including population-scale data sets from many European populations, to investigate genomic differentiation between males and females. Unlike in some other species, where high-quality genome assemblies exist but broad population sampling is lacking, the great tit offers a unique opportunity to study sex-based differentiation at both the genomic and population level. We identify significant differentiation at an autosomal locus on chromosome 5, which we hypothesise originates from sex-linked variation present on the sex chromosomes (Z and potentially W). By referencing genomic data from other songbirds with well-assembled sex chromosomes, we illustrate how autosomal loci may exhibit high sequence similarity to sex-linked regions. Our analyses demonstrate that uneven sex ratios in sampled populations can substantially bias differentiation metrics (e.g., F), potentially resulting in false-positive interpretations of adaptive differentiation. To mitigate such issues, we stress the importance of sex-aware study designs, including balanced sex sampling and explicitly incorporating sex as a covariate. Furthermore, while optimal study designs would include high-quality reference genomes from both sexes, we recommend, as a pragmatic and cost-effective alternative for labs with limited resources, generating a reference genome from the heterogametic sex (females in birds) to ensure both sex chromosomes are represented in mapping and analysis. Finally, we emphasise the need for rigorous validation of candidate loci to ensure accurate and biologically meaningful outcomes in evolutionary genomic studies.
性别特异性基因组分化是群体遗传学中一个关键但经常被忽视的因素。在这篇观点文章中，我们利用了可用于大山雀（Parus major）的大量基因组资源，包括来自许多欧洲种群的种群规模数据集，来研究雄性和雌性之间的基因组分化。与其他一些物种不同，虽然存在高质量的基因组组装，但缺乏广泛的种群采样，大山雀提供了一个独特的机会来在基因组和种群水平上研究基于性别的分化。我们在5号染色体上的一个常染色体位点发现了显著的分化，我们假设这起源于性染色体（Z以及可能的W）上存在的性连锁变异。通过参考其他具有良好组装性染色体的鸣禽的基因组数据，我们说明了常染色体位点如何可能与性连锁区域表现出高序列相似性。我们的分析表明，采样种群中不均衡的性别比例会严重影响分化指标（例如F），可能导致对适应性分化的假阳性解释。为了减轻这些问题，我们强调了性别意识研究设计的重要性，包括平衡的性别采样以及明确将性别作为一个协变量纳入。此外，虽然最佳的研究设计将包括来自两性的高质量参考基因组，但作为资源有限实验室的一种务实且具有成本效益的替代方案，我们建议从异配性别（鸟类中的雌性）生成参考基因组，以确保在映射和分析中两条性染色体都有体现。最后，我们强调需要对候选位点进行严格验证，以确保进化基因组学研究中获得准确且具有生物学意义的结果。
