Germline mutations are the raw material for natural selection, driving species evolution and the generation of earth's biodiversity. Without this driver of genetic diversity, life on earth would stagnate. Yet, it is a double-edged sword. An excess of mutations can have devastating effects on fitness and population viability. It is therefore one of the great challenges of molecular ecology to determine the rate and mechanisms by which these mutations accrue across the tree of life. Advances in high-throughput sequencing technologies are providing new opportunities for characterizing the rates and mutational spectra within species and populations thus informing essential evolutionary parameters such as the timing of speciation events, the intricacies of historical demography, and the degree to which lineages are subject to the burdens of mutational load. Here, we will focus on both the challenge and promise of whole-genome comparisons among parents and their offspring from known pedigrees for the detection of germline mutations as they arise in a single generation. The potential of these studies is high, but the field is still in its infancy and much uncertainty remains. Namely, the technical challenges are daunting given that pedigree-based genome comparisons are essentially searching for needles in a haystack given the very low signal to noise ratio. Despite the challenges, we predict that rapidly developing methods for whole-genome comparisons hold great promise for integrating empirically derived estimates of de novo mutation rates and mutation spectra across many molecular ecological applications.

中文翻译：

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从密切相关个体的全基因组比较中估计从头突变率的挑战和前景

种系突变是自然选择、推动物种进化和产生地球生物多样性的原材料。如果没有这种遗传多样性的驱动力，地球上的生命将停滞不前。然而，这是一把双刃剑。过多的突变会对健康和种群生存能力产生破坏性影响。因此，确定这些突变在生命之树中累积的速率和机制是分子生态学面临的巨大挑战之一。高通量测序技术的进步为表征物种和种群内的速率和突变谱提供了新的机会，从而为基本的进化参数提供信息，例如物种形成事件的时间、历史人口学的复杂性、以及谱系承受突变负荷的程度。在这里，我们将关注在父母及其来自已知谱系的后代之间进行全基因组比较的挑战和前景，以检测在一代中出现的种系突变。这些研究的潜力很大，但该领域仍处于起步阶段，仍存在许多不确定性。也就是说，鉴于基于谱系的基因组比较本质上是大海捞针，鉴于信噪比非常低，因此技术挑战令人生畏。尽管存在挑战，但我们预测，快速发展的全基因组比较方法对于整合许多分子生态应用中从头突变率和突变谱的经验得出的估计具有很大的前景。我们将重点关注在父母及其来自已知谱系的后代之间进行全基因组比较的挑战和前景，以检测在一代人中出现的种系突变。这些研究的潜力很大，但该领域仍处于起步阶段，仍存在许多不确定性。也就是说，鉴于基于谱系的基因组比较本质上是大海捞针，鉴于信噪比非常低，因此技术挑战令人生畏。尽管存在挑战，但我们预测，快速发展的全基因组比较方法对于整合许多分子生态应用中从头突变率和突变谱的经验得出的估计具有很大的前景。我们将重点关注在父母及其来自已知谱系的后代之间进行全基因组比较的挑战和前景，以检测在一代人中出现的种系突变。这些研究的潜力很大，但该领域仍处于起步阶段，仍存在许多不确定性。也就是说，鉴于基于谱系的基因组比较本质上是大海捞针，鉴于信噪比非常低，因此技术挑战令人生畏。尽管存在挑战，但我们预测，快速发展的全基因组比较方法对于整合许多分子生态应用中从头突变率和突变谱的经验得出的估计具有很大的前景。