Genomic analysis of inbreeding depression in the wild.

自达尔文以来，近亲繁殖的有害后果一直吸引着科学家。一个半世纪后，我们知道近亲繁殖衰退在二倍体生物中无处不在，其对广泛的性状，个体适应性和种群生存能力的关键影响的证据来自所有动物和植物王国。尽管近亲繁殖衰退具有巨大的意义，但人们对其最基本的特征知之甚少：基因组中有多少区域导致了近亲繁殖衰退？潜在的基因和等位基因是什么？它们的有害影响有多强？ 近亲繁殖的衰退在几代人中有多强烈？近亲繁殖抑郁症是在生命的早期还是晚期更严重？这些问题只能在野生种群中解决，在那里，适应性可以在自然环境的压力下测量，但直到最近，我们还缺乏基因组工具来回答这些问题。在这里，我提出了最深入的基因组调查近亲繁殖抑郁症在野生种群的日期。在世界上最好的表型自由生活研究群体之一，圣基尔达的Soay绵羊中，我将使用选定谱系成员的高密度SNP数据，结合群体范围的50k SNP芯片数据，在数千名研究个体的基因组中估算超过45万个SNP基因型。使用这个数据集，我将量化基因组中具有相同血统（IBD）的区域，以（1）调查大多数近亲繁殖衰退是否存在于最近近亲繁殖产生的长时间IBD中，（2）量化种群中胚胎致死等位基因的丰度，（三）在整个基因组中定位导致近亲繁殖衰退的遗传变异，并使用已建立的新的方法和（4）后续的大效应位点使用全基因组测序数据的基础基因和模式的选择涉及更深入的调查。

The detrimental consequences of inbreeding have fascinated scientists since Darwin. One and a half centuries later, we know that inbreeding depression is ubiquitous in diploid organisms and evidence for its critical impacts on a broad range of traits, individual fitness and population viability comes from all over the animal and plant kingdoms. Despite the enormous significance of inbreeding depression, little is known about its most fundamental features: How many regions of the genome contribute to inbreeding depression? What are the underlying genes and alleles and how strong are their deleterious effects? How strongly is inbreeding depression selected against over the generations? Is inbreeding depression stronger in earlier or in later life-stages? These questions can only be addressed in wild populations, where fitness can be measured under the pressures of natural environments, but until recently we lacked the genomic tools to answer them. Here, I propose the most in-depth genomic investigation of inbreeding depression in a wild population to date. In one of the best-phenotyped free-living study populations in the world, the Soay sheep of St Kilda, I will use high density SNP data for selected pedigree members in combination with population-wide 50k SNP chip data to impute more than 450,000 SNP genotypes throughout the genomes of thousands of study individuals. Using this dataset, I will quantify regions in the genome which are identical-by-descent (IBD) to (1) investigate whether most inbreeding depression resides in long stretches of IBD derived from recent inbreeding, (2) quantify the abundance of embryonic lethal alleles in the population, (3) locate the genetic variants causing inbreeding depression across the genome and quantify their effect sizes using a combination of established and novel methods and (4) follow-up large effect loci using whole-genome-sequencing data for a deeper investigation of the underlying genes and the mode of selection involved.