BRC-BIO: Detection of Nicrophorus orbicollis indirect genetic effects critical for fitness

坊间传闻，大多数人可以指出父母、兄弟姐妹、亲戚或朋友是如何影响他们成为的人的。当然，在许多非人类物种中，亲属或其他社会伙伴对个人特征的影响也可能很重要，如果这些影响是遗传的，它们可以在决定这些物种的进化命运方面发挥重要作用。然而，人们对社会伴侣相互影响的具体遗传机制知之甚少。在已知对社会影响至关重要的有机体中，埋葬甲虫通过部分消化的腐肉的反流为其后代提供先进的父母照顾。该项目将使用全基因组测序来识别母亲的基因，这些基因会导致一组可能与健康有关的后代特征的变异。该项目将对一名研究生和许多本科生进行现代分子、生物信息学和统计学技术方面的培训，并将为奥斯汀佩伊州立大学的学生提供以前无法获得的课堂计算资源。此外，还将邀请外部演讲者讨论该项目中使用的技术如何通过医学、农业和社会科学的进步来影响日常生活，使学生有机会将实验室中发生的事情与更广阔的世界联系起来。被称为间接遗传效应(IGE)的社会影响被理论上在表型进化中扮演着特别重要的角色。然而，由于缺乏找到产生IGES的特定等位基因的能力，IGES的实证研究一直受到阻碍。找到这些等位基因可以回答三个主要问题。首先，IGES的结构在很大程度上是多基因的，还是有任何主要的影响等位基因发挥作用？其次，发现了哪些基因可以赋予IGES，识别这些基因和它们的作用途径，能否得出关于分子机制的一般性结论？第三，IGES和更标准的个体对表型的基因贡献(直接遗传效应；DGE)之间的遗传相关性的分子性质是什么？该项目将产生1500个家庭的埋葬甲虫使用交叉养育，这样母亲就可以抚养无关的后代。每个母亲都将通过低覆盖率的基因组测序进行基因分型，并将使用全基因组关联研究(GWAS)来使用母亲的基因型别来预测后代的表型。还将对每个家庭的三个后代进行测序，以便可以与IGES一起估计DGE，从而能够估计它们之间的遗传相关性。除了解决上述问题外，该项目还将使用CRISPR/CAS9进行功能基因组研究，并将为等位基因频率随时间和空间变化的群体遗传学研究产生新的假设。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Anecdotally, most people can point to how a parent, sibling, relative, or friend has influenced the person they have become. In many non-human species, of course, the influence of relatives or other social partners on an individual’s characteristics can also be important, and if those influences are genetic, they can play a major role in determining the evolutionary fates of those species. However, little is known about the specific genetic mechanisms by which social partners can affect each other. Among organisms where social influences are known to be critical are burying beetles, which provide advanced parental care to their offspring through the regurgitation of partially digested carrion. This project will use whole genome sequencing to identify the genes in mothers that cause variation in a set of offspring traits that may be linked to fitness. The project will train one graduate student and numerous undergraduates in modern molecular, bioinformatic, and statistical techniques, and will generate computational resources for the classroom previously unavailable to students at Austin Peay State University. In addition, outside speakers will be brought in to discuss how techniques like those used in this project have the potential to affect everyday life through advances in medicine, agriculture, and social science, giving students the chance to connect what goes on in the lab to the broader world.Social influences, known as indirect genetic effects (IGE), are theorized to play especially important roles in phenotypic evolution. However, the empirical study of IGEs has been hampered by a lack of ability to find the specific alleles that generate them. Finding these alleles can answer three major questions. First, is the architecture of IGEs largely polygenic, or do any major effect alleles play a role? Second, what genes are found to confer IGEs, and can any generalizable conclusions about molecular mechanisms come from identifying these genes and the pathways in which they operate? And third, what is the molecular nature of genetic correlations between IGEs and more standard individual contributions of genotype to phenotpe (direct genetic effects; DGE)? This project will generate 1500 families of the burying beetle Nicrophorus orbicollis using cross-fostering, so that mothers rear unrelated offspring. Each mother will be genotyped via low-coverage genome sequencing, and a genome-wide association study (GWAS) will be used to predict offspring phenotypes using maternal genotypes. Three offspring from each family will also be sequenced so that DGEs can be estimated alongside IGEs, allowing for estimation of genetic correlations between them. In addition to addressing the questions raised above, the project will will enable functional genomic studies using CRISPR/Cas9 and will generate new hypotheses for population genetic studies of allele frequency change over space and time.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.