Hidenki Innan and Yuseob Kim Pattern of Polymorphism After Strong Artificial Selection in a Domestication Event Hidenki Innan and Yuseob Kim A Summary By William Dotson and Danny Rose

Outline of the Presentation Background Information Background Information Experimental Methods and Results Experimental Methods and Results Discussion and Implications Discussion and Implications

Background Information Study Objective –Determine a model for the process of strong artificial selection during a domestication event. –Artificial Selection  Differs from advantageous mutant selection –i.e. acts on previously neutral allele*  Domestication Events –Causes fixation of a predetermined advantageous allele  i.e. dogs, cows, barley, etc.

Background Information Cont. Applications Find domestication genes primarily in crops such as corn and rice  Future crop improvements –Disease models –Greater crop yields

Experimental Theory Linkage Disequilibrium Equilibrium – the genotype of a chromosome at one locus is independent of its genotype at the other locus   Disequilibrium- there is a nonrandom association between a chromosome’s genotype at one region and its genotype at the other region – –Selection* – –Genetic drift – –Population admixture   Can be calculated as a numerical value.

Experimental Theory Selection and Linkage Disequilibrium – –Artificial selection puts unequal pressure on a what was likely previously a neutral allele   When the allele is selected for, it carries a random selection of surrounding genes with it – –Genotypes from region to region in each generation are no longer independent of each other – –These quantifiable effects are used as signatures for selected genes   Example – young allele at high frequency

Experimental Methods Measurements of Artificial Selection – –Polymorphism   3 measures of polymorphism in this study -  S variation in segregating site   variation of pairwise nucleotide differences  H homozygosity of the derived allele per site   Low amounts of polymorphism suggest the influence of selection (signature) Using history of frequencies of the allele classes, a model and simulation were developed

Experimental Methods Simulation of a Domestication Event – Bottleneck Neutral Allele in Wild Progenitor Population (Genetic Drift) Subset Founder Population and Artificial Selection Begins (t d ) Ancestral Population N 2 Current Population N 1

Experimental Methods Basis model used for experimental simulations to investigate patterns of DNA polymorphism after domestication with and without selection.

Simulation 1 Polymorphism with Selection – –Constant population size – –5000 Replications – –Polymorphism is represented as  , which is ideally equal to 4N  in a constant size population – –Several initial frequencies were studied and compared with the standard selective sweep model – –Different strengths of selection were compared in the second figure.

Simulation 1 Standard Selective Sweep Model

Simulation 2 Two simulations were used to determine the joint effects of selection and population bottleneck The severity of the bottleneck differs in each case. The level of polymorphism is reduced by the bottleneck regardless of the effect of selection The qualitative effect of p is almost identical in both models

Simulation 2

Simulation 3 Measured the effects of different values for initial time of selection (t d ) ancestral population size (N 2 ) and current population size (N 0 ) on the expected level of polymorphism

Simulation 3

Simulation 4 Individual Polymorphisms in 8 different simulations Polymorphism decreases as you get further away from the target site Target site is at 0.5

Simulation 4

Experimental Methods Statistical Tests for Selection Tajima’s (D) Fay and Wu’s (H) Hudson – Kreitman – Aguade (HKA) These statistical tests were used to analyze the simulations to detect a signature of selection. These tests supported the theoretical model in that it followed the patterns of polymorphism and selection.

Discussion and Implications Models were developed to measure the level of polymorphism and subsequently detect genes that were selected for through domestication events. Initial frequencies of alleles greatly affects the likelihood that evidence for selection can be detected from patterns of polymorphism. – –Difficult to detect many genes involved in domestication It is likely that these patterns will be used to detect domesticated genes in future studies, but a more robust model will be needed in cases when the initial p is high. Implication previously discussed – –Crop yields – –Diseases