Mutation is the ultimate source of all genetic novelty and the cause of heritable genetic disorders. Mutational burden has been linked to complex disease, including neurodevelopmental disorders such as schizophrenia and autism. The rate of mutation is a fundamental genomic parameter and direct estimates of this parameter have been enabled by accurate comparisons of whole-genome sequences between parents and offspring. Studies in humans have revealed that the paternal age at conception explains most of the variation in mutation rate: Each additional year of paternal age in humans leads to approximately 1.5 additional inherited mutations. Here, we present an estimate of the de novo mutation rate in the rhesus macaque (Macaca mulatta) using whole-genome sequence data from 32 individuals in four large pedigrees. We estimated an average mutation rate of 0.58 × 10⁻⁸ per base pair per generation (at an average parental age of 7.5 yr), much lower than found in direct estimates from great apes. As in humans, older macaque fathers transmit more mutations to their offspring, increasing the per generation mutation rate by 4.27 × 10⁻¹⁰ per base pair per year. We found that the rate of mutation accumulation after puberty is similar between macaques and humans, but that a smaller number of mutations accumulate before puberty in macaques. We additionally investigated the role of paternal age on offspring sociability, a proxy for normal neurodevelopment, by studying 203 male macaques in large social groups.

中文翻译：

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猕猴的父本年龄与种系突变的积累呈正相关，但与后代的社交能力无关。

突变是所有遗传新事物的最终来源，也是遗传性遗传疾病的原因。突变负担已与复杂的疾病相关，包括神经发育障碍，例如精神分裂症和自闭症。突变率是一个基本的基因组参数，通过精确比较亲本和后代之间的全基因组序列，可以直接估计该参数。对人类的研究表明，受孕时的父本年龄可以解释大多数突变率变异：人类每增加一年的父本年龄，就会导致大约1.5个额外的遗传突变。在这里，我们提出了恒河猴（猕猴）的从头突变率的估计）使用来自四个大型谱系中32个个体的全基因组序列数据。我们估计每代碱基对的平均突变率为0.58×10 ^-8（在父母的平均年龄为7.5岁时），远低于大猿类的直接估计值。与人类一样，猕猴的父亲向其后代传播更多的突变，每年每碱基对的每代突变率增加4.27×10 ^-10。我们发现，猕猴和人类在青春期后的突变积累率相似，但是在猕猴中青春期之前的突变积累的数量较少。我们还通过研究大型社会群体中的203只雄性猕猴，进一步研究了父亲年龄对后代社交能力（正常神经发育的代表）的作用。