The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA.
Science. 2024 Nov 22;386(6724):eadn0609. doi: 10.1126/science.adn0609.
Previous studies suggested that the copy number of the human salivary amylase gene, , correlates with starch-rich diets. However, evolutionary analyses are hampered by the absence of accurate, sequence-resolved haplotype variation maps. We identified 30 structurally distinct haplotypes at nucleotide resolution among 98 present-day humans, revealing that the coding sequences of copies are evolving under negative selection. Genomic analyses of these haplotypes in archaic hominins and ancient human genomes suggest that a common three-copy haplotype, dating as far back as 800,000 years ago, has seeded rapidly evolving rearrangements through recurrent nonallelic homologous recombination. Additionally, haplotypes with more than three copies have significantly increased in frequency among European farmers over the past 4000 years, potentially as an adaptive response to increased starch digestion.
先前的研究表明，人类唾液淀粉酶基因的拷贝数与富含淀粉的饮食有关。然而，由于缺乏准确的、基于序列的单倍型变异图谱，进化分析受到了阻碍。我们在 98 名当代人类中以核苷酸分辨率确定了 30 种结构上不同的单倍型，揭示了 拷贝的编码序列在受到负选择。对古人类和古代人类基因组中这些单倍型的基因组分析表明，一个共同的三拷贝单倍型可以追溯到 80 万年前，通过反复的非等位基因同源重组快速产生进化中的重排。此外，在过去的 4000 年里，拥有三个以上 拷贝的单倍型在欧洲农民中的频率显著增加，这可能是对淀粉消化增加的一种适应反应。
