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Elucidating the relationship between heterozygosity and fitness in a natural vertebrate population

阐明自然脊椎动物种群杂合性和适应性之间的关系

基本信息

批准号：
243472732
负责人：
Professor Dr. Joseph Hoffman
金额：
--
依托单位：
Department of Animal and Plant Sciences
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/243472732?language=en
关键词：
Elucidating relationship between heterozygosity fitness

项目摘要

Many important fitness traits including parasite resistance, survivorship and reproductive success often correlate with heterozygosity in natural populations. Where documented, such heterozygosity fitness correlations (HFCs) have the potential to influence interactions between pathogens and their hosts and the evolution of mate choice. However, because most studies use only around ten microsatellite markers, we do not yet know which of two possible mechanisms is most important nor the types of gene involved. Fortunately, Next Generation Sequencing technologies allow the development of gene-targeted Single Nucleotide Polymorphisms (SNPs) which, if screened in a species where high-quality fitness measures can be gathered, should for the first time allow direct links to be made between fitness and the heterozygosity of literally thousands of genes. I will exploit just such a system, the Antarctic fur seal (Arctocephalus gazella), in which an exceptionally detailed long term study has already revealed HFCs for numerous traits.By screening 6000 SNPs in 1500 female seals for which detailed fitness data are available, I will distinguish between two primary hypotheses proposed to explain HFCs. Under the general effects hypothesis, HFCs are ascribed to inbreeding depression, with marker heterozygosity providing a surrogate measure of an individual inbreeding coefficient f. Here, additional markers should improve the estimate of f and the relationship between fitness and average marker heterozygosity will strengthen. Under the alternative local effect model, which invokes chance linkage between individual markers and genes experiencing balancing selection, heterozygosity is uncorrelated among loci such that more markers will if anything reduce HFC strength as the contribution of any one marker becomes progressively diluted.In practice, local effects are likely to be present even if inbreeding depression is involved, but as with the primary mechanism these are poorly understood. For example, are the underlying genes diverse or mostly related to immunity or growth? To explore these and related questions, SNPs targeted within specific classes of genes identified by comparison with the dog genome will be analysed individually and as haplotypes for associations with fitness. Local effects will then be fine-mapped, by constructing the first marine mammal linkage map and through comparative genomics with the dog, to determine which genomic regions are involved and what specific genes they contain. The resulting dataset of over 9000000 SNP genotypes will thereby provide an unprecedented window on how genetic variability impacts key fitness traits in a natural mammalian population.

许多重要的适合度性状，包括寄生虫抗性，生存和繁殖成功往往与自然群体的杂合性。在文件中，这种杂合性适合度相关性（HFC）有可能影响病原体和它们的宿主之间的相互作用以及配偶选择的进化。然而，由于大多数研究只使用了大约10个微卫星标记，我们还不知道两种可能的机制中哪一种最重要，也不知道涉及的基因类型。幸运的是，下一代测序技术允许开发基因靶向单核苷酸多态性（SNP），如果在可以收集高质量适应性指标的物种中进行筛选，应该首次允许在数千个基因的适应性和杂合性之间建立直接联系。我将利用这样一个系统，南极海狗（Arctocephalus gazella），其中一个非常详细的长期研究已经揭示了HFCs的许多traits.By筛选6000单核苷酸多态性在1500名女性海豹的详细健身数据，我将区分两个主要的假设提出来解释HFCs。根据一般效应假设，氢氟碳化合物归因于近亲繁殖衰退，标记杂合性提供了个体近亲繁殖系数f的替代测量。在这里，额外的标记应改善估计的f和适应度和平均标记杂合度之间的关系将加强。在替代局部效应模型下，该模型调用个体标记和经历平衡选择的基因之间的偶然连锁，杂合性在基因座之间是不相关的，使得更多的标记将降低HFC强度，因为任何一个标记的贡献变得逐渐稀释。但与主要机制一样，对这些机制的了解很少。例如，潜在的基因是多样的，还是主要与免疫或生长有关？为了探索这些和相关的问题，通过与狗的基因组比较确定的特定类别的基因内的SNP将被单独分析，并作为单倍型与健身的关联。然后将通过构建第一个海洋哺乳动物连锁图谱并通过与狗的比较基因组学来精细绘制局部影响，以确定涉及哪些基因组区域以及它们包含哪些特定基因。由此产生的超过9000000 SNP基因型的数据集，从而提供了一个前所未有的窗口遗传变异如何影响关键健身性状在自然哺乳动物种群。