Griffiths Robert C, Jenkins Paul A, Lessard Sabin
Department of Statistics, University of Oxford, United Kingdom.
Department of Statistics, University of Warwick, United Kingdom; Department of Computer Science, University of Warwick, United Kingdom.
Theor Popul Biol. 2016 Dec;112:126-138. doi: 10.1016/j.tpb.2016.08.007. Epub 2016 Sep 1.
Duality plays an important role in population genetics. It can relate results from forwards-in-time models of allele frequency evolution with those of backwards-in-time genealogical models; a well known example is the duality between the Wright-Fisher diffusion for genetic drift and its genealogical counterpart, the coalescent. There have been a number of articles extending this relationship to include other evolutionary processes such as mutation and selection, but little has been explored for models also incorporating crossover recombination. Here, we derive from first principles a new genealogical process which is dual to a Wright-Fisher diffusion model of drift, mutation, and recombination. The process is reminiscent of the ancestral recombination graph, a widely-used multilocus genealogical model, but here ancestral lineages are typed and transition rates are regarded as being conditioned on an observed configuration at the leaves of the genealogy. Our approach is based on expressing a putative duality relationship between two models via their infinitesimal generators, and then seeking an appropriate test function to ensure the validity of the duality equation. This approach is quite general, and we use it to find dualities for several important variants, including both a discrete L-locus model of a gene and a continuous model in which mutation and recombination events are scattered along the gene according to continuous distributions. As an application of our results, we derive a series expansion for the transition function of the diffusion. Finally, we study in further detail the case in which mutation is absent. Then the dual process describes the dispersal of ancestral genetic material across the ancestors of a sample. The stationary distribution of this process is of particular interest; we show how duality relates this distribution to haplotype fixation probabilities. We develop an efficient method for computing such probabilities in multilocus models.
对偶性在群体遗传学中起着重要作用。它可以将等位基因频率演化的正向时间模型的结果与反向时间系谱模型的结果联系起来;一个著名的例子是遗传漂变的赖特 - 费希尔扩散与其系谱对应物——合并过程之间的对偶性。已经有许多文章将这种关系扩展到包括突变和选择等其他进化过程,但对于也纳入交叉重组的模型却鲜有探讨。在这里,我们从第一原理推导出一个新的系谱过程,它与一个包含漂变、突变和重组的赖特 - 费希尔扩散模型对偶。这个过程让人联想到祖先重组图,一个广泛使用的多位点系谱模型,但这里祖先谱系是有类型的,并且转移速率被视为以系谱叶节点处的观察配置为条件。我们的方法基于通过两个模型的无穷小生成元来表达它们之间假定的对偶关系,然后寻找一个合适的测试函数以确保对偶方程的有效性。这种方法相当通用,我们用它来找到几个重要变体的对偶性,包括一个基因的离散L位点模型和一个连续模型,在该连续模型中突变和重组事件根据连续分布沿着基因散布。作为我们结果的一个应用,我们推导出扩散转移函数的级数展开。最后,我们进一步详细研究不存在突变的情况。那么对偶过程描述了祖先遗传物质在样本祖先中的扩散。这个过程的平稳分布特别令人感兴趣;我们展示了对偶性如何将这个分布与单倍型固定概率联系起来。我们开发了一种在多位点模型中计算此类概率的有效方法。