Williams syndrome is a complex condition resulting from the heterozygous deletion of nearly 30 genes in chromosome 7. However, precise genotype-to-phenotype mappings are not available for most of its distinctive features. Because WS entails changes in the expression patterns of multiple genes outside the WS region, it can be expected that many other genes besides the deleted genes contribute to this condition. In this paper, we hypothesise that genes that have changed recently in our history could account for some key aspects of the WS phenotype, because of the robust link that exists between human evolution and complex, human-specific diseases. Supporting this view, we have found that protein-coding genes that are dysregulated in the blood of subjects with WS are significantly enriched in protein-coding genes that have been positively selected in our species compared to extinct hominins. These genes play biological roles and are expressed in body regions of relevance for the WS phenotype. We conclude that the genes we highlight in the paper should be regarded as important etiological factors of the WS clinical profile.

威廉姆斯综合症是由7号染色体中近30个基因的杂合缺失导致的复杂疾病。但是，对于大多数独特特征，尚无精确的基因型到表型作图。由于WS导致WS区域以外的多个基因的表达模式发生变化，因此可以预期除缺失的基因外还有许多其他基因也导致了这种情况。在本文中，我们假设，由于人类进化与复杂的，特定于人类的疾病之间存在牢固的联系，因此在我们历史上最近发生变化的基因可以解释WS表型的某些关键方面。支持这种观点，我们已经发现，WS受试者血液中失调的蛋白质编码基因与已经灭绝的人豆素相比，在我们物种中已被积极选择的蛋白质编码基因中明显富集。这些基因发挥生物学作用，并在与WS表型相关的身体部位表达。我们得出的结论是，我们在本文中突出显示的基因应被视为WS临床概况的重要病因。