heory
A new test for balancing selection
In this section, we provide a basic overview of a new test for balancing selection, and we describe the method in greater detail in the sections entitled Kaplan-Darden-Hudson model, Solving the recursion relation, A composite likelihood ratio test based on polymorphism and substitution, and A composite likelihood ratio test based on frequency spectra and substitutions sections. We have developed a new statistical method for detecting balancing selection, which is based on the model of Kaplan, Darden, and Hudson [20], [21] (full details provided in the Kaplan-Darden-Hudson model section). Under this model, we calculate the expected distribution of allele frequencies using simulations, and approximate the probability of observing a fixed difference or polymorphism at a site as a function of its genomic distance to a putative site under balancing selection. Using these calculations, we construct composite likelihood tests that can be used to identify sites under balancing selection, similar to the approaches by Kim and Stephan [23] and Nielsen et al. [26] for detecting selective sweeps.
Basic framework
Consider a biallelic site An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e005.jpg that is under strong balancing selection and maintains an allele An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e006.jpg at frequency An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e007.jpg and an allele An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e008.jpg at frequency An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e009.jpg. Consider a neutral locus An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e010.jpg that is linked to the selected locus An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e011.jpg. Denote the scaled recombination rate between the selected locus and the neutral locus as An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e012.jpg, where An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e013.jpg is the diploid population size and An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e014.jpg is the per-generation recombination rate. Assume we have a sample of An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e015.jpg genomes from an ingroup species (e.g., humans) and a single genome from an outgroup species (e.g., chimpanzee). From these data, we can estimate the genome-wide expected coalescence time An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e016.jpg between the ingroup and outgroup species (see Materials and Methods for details). Also, under the Kaplan-Darden-Hudson model, we can obtain the expected tree length An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e017.jpg and height An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e018.jpg for a sample of An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e019.jpg lineages affected by balancing selection by solving a set of recursive equations using the numerical approach described in the Solving the recursion relation. The relationship among An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e020.jpg, An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e021.jpg, and An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e022.jpg is depicted in Figure 1A. Assuming a small mutation rate, the probability that a site is polymorphic under a model of balancing selection, given that it contains either a polymorphism or a substitution (fixed difference), is
equation image
heoryA new test for balancing selectionIn this section, we provide a basic overview of a new test for balancing selection, and we describe the method in greater detail in the sections entitled Kaplan-Darden-Hudson model, Solving the recursion relation, A composite likelihood ratio test based on polymorphism and substitution, and A composite likelihood ratio test based on frequency spectra and substitutions sections. We have developed a new statistical method for detecting balancing selection, which is based on the model of Kaplan, Darden, and Hudson [20], [21] (full details provided in the Kaplan-Darden-Hudson model section). Under this model, we calculate the expected distribution of allele frequencies using simulations, and approximate the probability of observing a fixed difference or polymorphism at a site as a function of its genomic distance to a putative site under balancing selection. Using these calculations, we construct composite likelihood tests that can be used to identify sites under balancing selection, similar to the approaches by Kim and Stephan [23] and Nielsen et al. [26] for detecting selective sweeps.Basic frameworkConsider a biallelic site An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e005.jpg that is under strong balancing selection and maintains an allele An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e006.jpg at frequency An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e007.jpg and an allele An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e008.jpg at frequency An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e009.jpg. Consider a neutral locus An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e010.jpg that is linked to the selected locus An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e011.jpg. Denote the scaled recombination rate between the selected locus and the neutral locus as An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e012.jpg, where An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e013.jpg is the diploid population size and An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e014.jpg is the per-generation recombination rate. Assume we have a sample of An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e015.jpg genomes from an ingroup species (e.g., humans) and a single genome from an outgroup species (e.g., chimpanzee). From these data, we can estimate the genome-wide expected coalescence time An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e016.jpg between the ingroup and outgroup species (see Materials and Methods for details). Also, under the Kaplan-Darden-Hudson model, we can obtain the expected tree length An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e017.jpg and height An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e018.jpg for a sample of An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e019.jpg lineages affected by balancing selection by solving a set of recursive equations using the numerical approach described in the Solving the recursion relation. The relationship among An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e020.jpg, An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e021.jpg, and An external file that holds a picture, illustration, etc. Object name is pgen.1004561.e022.jpg is depicted in Figure 1A. Assuming a small mutation rate, the probability that a site is polymorphic under a model of balancing selection, given that it contains either a polymorphism or a substitution (fixed difference), isequation image
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heory
ใหม่ทดสอบสมดุลเลือก
ในส่วนนี้ , เราให้ภาพรวมพื้นฐานของการทดสอบใหม่สำหรับการเลือก และบรรยายถึงวิธีการในรายละเอียดมากขึ้นในส่วนสิทธิ Kaplan Darden ฮัดสันรูปแบบการแก้ปัญหาความสัมพันธ์การเรียกซ้ำ , คอมโพสิตและโอกาสทดสอบอัตราส่วนตามรูปแบบการและโอกาสทดสอบอัตราส่วนผสมตามสเปกตรัมความถี่และการแทนส่วน เราได้พัฒนาวิธีการใหม่สำหรับการตรวจหาความสมดุลทางเลือก ซึ่งขึ้นอยู่กับรูปแบบของ กาแพน , Darden , และฮัดสัน [ 20 ] , [ 21 ] ( รายละเอียดให้ในส่วนของ Kaplan Darden ฮัดสันรุ่น ) ในรุ่นนี้เราสามารถคาดหวังกระจายความถี่โดยใช้การจำลองและประมาณความน่าจะเป็นของการสังเกตความแตกต่างหรือคงที่ ) ที่เว็บไซต์เป็นฟังก์ชันของระยะทางไปยังเว็บไซต์ที่มีการแสดงออกในการเลือก โดยใช้การคำนวณเหล่านี้เราสร้างแบบทดสอบความน่าจะเป็นคอมโพสิตที่สามารถใช้เพื่อระบุเว็บไซต์ภายใต้ดุล การเลือกคล้ายกับวิธีโดยคิมและสตีเฟ่น [ 23 ] และ Nielsen et al . [ 26 ] สำหรับการเลือกพื้นฐานกรอบกวาด .
พิจารณา biallelic เว็บไซต์ภายนอกไฟล์ที่มีรูปภาพ , ภาพประกอบ ฯลฯ วัตถุชื่อ pgen.1004561.e005.jpg ที่อยู่ภายใต้การรักษาสมดุลและแข็งแรงในแฟ้มภายนอกนั้นยังคงภาพ , ภาพประกอบ ฯลฯ วัตถุชื่อ pgen.1004561 .e006.jpg ความถี่ภายนอกไฟล์ที่มีรูปภาพ , ภาพประกอบ ฯลฯ วัตถุชื่อ pgen.1004561.e007.jpg และปัจจัยเสี่ยงภายนอกไฟล์ที่มีรูปภาพ , ภาพประกอบ ฯลฯ วัตถุชื่อ pgen.1004561.e008.jpg ความถี่ภายนอกไฟล์ที่มีรูปภาพ , ภาพประกอบ ฯลฯ วัตถุชื่อ pgen.1004561.e009.jpg . พิจารณาตนเป็นกลางภายนอกไฟล์ที่เก็บรูปภาพประกอบ ฯลฯ วัตถุชื่อ pgen.1004561.e010.jpg ที่เชื่อมโยงกับความเชื่ออำนาจภายนอกที่เลือกไฟล์ที่มีรูปภาพ , ภาพประกอบ ฯลฯ วัตถุชื่อ pgen.1004561.e011.jpg . แสดงถึงการปรับอัตราระหว่างความเชื่อและความเชื่อที่เป็นกลางเป็นภายนอกไฟล์ที่มีรูปภาพ , ภาพ , ฯลฯ เป็นชื่อ pgen.1004561.e012.jpg วัตถุ ,
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