Increasing habitat fragmentation leads to wild populations becoming small, isolated, and threatened by inbreeding depression. However, small populations may be able to purge recessive deleterious alleles as they become expressed in homozygotes, thus reducing inbreeding depression and increasing population viability. We used whole-genome sequences from 57 tigers to estimate individual inbreeding and mutation load in a small–isolated and two large–connected populations in India. As expected, the small–isolated population had substantially higher average genomic inbreeding (F_ROH = 0.57) than the large–connected (F_ROH = 0.35 and F_ROH = 0.46) populations. The small–isolated population had the lowest loss-of-function mutation load, likely due to purging of highly deleterious recessive mutations. The large populations had lower missense mutation loads than the small–isolated population, but were not identical, possibly due to different demographic histories. While the number of the loss-of-function alleles in the small–isolated population was lower, these alleles were at higher frequencies and homozygosity than in the large populations. Together, our data and analyses provide evidence of 1) high mutation load, 2) purging, and 3) the highest predicted inbreeding depression, despite purging, in the small–isolated population. Frequency distributions of damaging and neutral alleles uncover genomic evidence that purifying selection has removed part of the mutation load across Indian tiger populations. These results provide genomic evidence for purifying selection in both small and large populations, but also suggest that the remaining deleterious alleles may have inbreeding-associated fitness costs. We suggest that genetic rescue from sources selected based on genome-wide differentiation could offset any possible impacts of inbreeding depression.

栖息地日益破碎化导致野生种群规模缩小、孤立，并受到近亲繁殖衰退的威胁。然而，当隐性有害等位基因在纯合子中表达时，小群体可能能够清除它们，从而减少近交抑制并提高群体生存能力。我们使用 57 只老虎的全基因组序列来估计印度一个小型孤立种群和两个大型关联种群中的个体近交和突变负荷。正如预期的那样，小型孤立种群的平均基因组近交（ F _ROH = 0.57）远高于大型连接种群（ F _ROH = 0.35 和F _ROH = 0.46）。小规模隔离群体的功能丧失突变负荷最低，可能是由于清除了高度有害的隐性突变。大群体的错义突变负荷比小隔离群体低，但并不完全相同，可能是由于不同的人口历史。虽然小型隔离群体中功能​​丧失等位基因的数量较低，但这些等位基因的频率和纯合性高于大型群体。总之，我们的数据和分析提供了以下证据：1）高突变负荷，2）清除，以及 3）尽管进行了清除，但在小型隔离种群中预测的近交衰退仍是最高的。破坏性和中性等位基因的频率分布揭示了基因组证据，表明纯化选择消除了印度虎种群的部分突变负荷。 这些结果为小群体和大群体中的纯化选择提供了基因组证据，但也表明剩余的有害等位基因可能具有与近交相关的适应性成本。我们建议，根据全基因组分化选择的来源进行基因拯救可以抵消近亲繁殖衰退的任何可能影响。