Reference genome resources associated with the project: Functional genetic diversity is correlated with intensity of genetic drift in populations of an endangered rattlesnake

Theory predicts that genetic erosion in small, isolated populations of endangered species can be assessed using estimates of neutral genetic variation reflecting long-term impacts of genetic drift, yet this widely used approach has been questioned in the genomics era. Here we leverage a chromosome-level assembly and whole genome resequencing data (N=110 individuals) from an endangered rattlesnake (Sistrurus catenatus) to evaluate the relationship between genome-wide neutral and functional diversity over long- and short-term timescales. As predicted for populations at long-term equilibrium, we found a positive correlation between population-level estimates of neutral genetic diversity (π) and the mean number of highly detrimental loss-of-function mutations, and a negative relationship between neutral genetic diversity and an estimate of genetic load. In contrast, we found only a weak, non-significant positive correlation between levels of neutral and adaptive variation. Additional analyses using estimates of drift at more recent time scales (> 100 generations) show expected correlations between both measures of genetic load, but a lack of a significant correlation with levels of adaptive variation. Individual-based demographic metrics that capture drift impacts over recent time scales confirm these results. Broadly, our results confirm that estimates of diversity and demography based on neutral genetic variation provide an accurate measure of a key component of genetic erosion – genetic load – in populations of a threatened vertebrate. Our findings also provide nuance to the neutral-functional diversity controversy by demonstrating that neutral genetic diversity is useful in predicting some, but not all, components of functional genetic diversity.

理论预测，濒危物种小型孤立种群的遗传侵蚀（genetic erosion）可通过反映遗传漂变（genetic drift）长期影响的中性遗传变异（neutral genetic variation）估算值开展评估，但这一被广泛应用的研究方法在基因组学（genomics）时代受到了质疑。本研究以濒危响尾蛇（Sistrurus catenatus）为研究对象，借助其染色体水平基因组组装（chromosome-level assembly）与全基因组重测序（whole genome resequencing）数据（样本量N=110），在长、短两个时间尺度下评估全基因组范围内中性多样性与功能多样性之间的关联。正如长期平衡种群的理论预测所示，我们发现种群水平的中性遗传多样性估算值（π）与高有害性功能丧失突变（loss-of-function mutations）的平均数量呈正相关，而中性遗传多样性与遗传负荷（genetic load）的估算值呈负相关。与之相对，我们仅观察到中性变异与适应性变异水平之间存在微弱且无统计学显著性的正相关。利用时间尺度大于100代的近期遗传漂变估算值开展的补充分析显示，两类遗传负荷指标均呈现预期的相关性，但与适应性变异水平未出现显著关联。基于个体的、可反映近期遗传漂变影响的种群统计指标（demographic metrics）验证了上述结果。总体而言，本研究结果证实，基于中性遗传变异的多样性与种群统计指标估算值，可准确衡量受威胁脊椎动物种群中遗传侵蚀的关键组成部分——遗传负荷。本研究结果还为中性-功能多样性争议（neutral-functional diversity controversy）提供了精细化视角：中性遗传多样性可用于预测功能遗传多样性的部分组分，但并非全部组分。