TY - JOUR
T1 - Demographically-Based Evaluation of Genomic Regions under Selection in Domestic Dogs
AU - Freedman, Adam H.
AU - Schweizer, Rena M.
AU - Ortega-Del Vecchyo, Diego
AU - Han, Eunjung
AU - Davis, Brian W.
AU - Gronau, Ilan
AU - Silva, Pedro M.
AU - Galaverni, Marco
AU - Fan, Zhenxin
AU - Marx, Peter
AU - Lorente-Galdos, Belen
AU - Ramirez, Oscar
AU - Hormozdiari, Farhad
AU - Alkan, Can
AU - Vilà, Carles
AU - Squire, Kevin
AU - Geffen, Eli
AU - Kusak, Josip
AU - Boyko, Adam R.
AU - Parker, Heidi G.
AU - Lee, Clarence
AU - Tadigotla, Vasisht
AU - Siepel, Adam
AU - Bustamante, Carlos D.
AU - Harkins, Timothy T.
AU - Nelson, Stanley F.
AU - Marques-Bonet, Tomas
AU - Ostrander, Elaine A.
AU - Wayne, Robert K.
AU - Novembre, John
N1 - Publisher Copyright: © 2016, Public Library of Science. All Rights Reserved.
PY - 2016/3
Y1 - 2016/3
N2 - Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rdtop hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers.
AB - Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rdtop hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers.
UR - http://www.scopus.com/inward/record.url?scp=84962386273&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pgen.1005851
DO - https://doi.org/10.1371/journal.pgen.1005851
M3 - مقالة
SN - 1553-7390
VL - 12
JO - PLoS Genetics
JF - PLoS Genetics
IS - 3
M1 - e1005851
ER -