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Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes

Gene flow between previously differentiated populations during the founding of an admixed or hybrid population has the potential to introduce adaptive alleles into the new population. If the adaptive allele is common in one source population, but not the other, then as the adaptive allele rises in f...

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Autores principales: Hamid, Iman, Korunes, Katharine L, Schrider, Daniel R, Goldberg, Amy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116606/
https://www.ncbi.nlm.nih.gov/pubmed/36947126
http://dx.doi.org/10.1093/molbev/msad074
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author Hamid, Iman
Korunes, Katharine L
Schrider, Daniel R
Goldberg, Amy
author_facet Hamid, Iman
Korunes, Katharine L
Schrider, Daniel R
Goldberg, Amy
author_sort Hamid, Iman
collection PubMed
description Gene flow between previously differentiated populations during the founding of an admixed or hybrid population has the potential to introduce adaptive alleles into the new population. If the adaptive allele is common in one source population, but not the other, then as the adaptive allele rises in frequency in the admixed population, genetic ancestry from the source containing the adaptive allele will increase nearby as well. Patterns of genetic ancestry have therefore been used to identify post-admixture positive selection in humans and other animals, including examples in immunity, metabolism, and animal coloration. A common method identifies regions of the genome that have local ancestry “outliers” compared with the distribution across the rest of the genome, considering each locus independently. However, we lack theoretical models for expected distributions of ancestry under various demographic scenarios, resulting in potential false positives and false negatives. Further, ancestry patterns between distant sites are often not independent. As a result, current methods tend to infer wide genomic regions containing many genes as under selection, limiting biological interpretation. Instead, we develop a deep learning object detection method applied to images generated from local ancestry-painted genomes. This approach preserves information from the surrounding genomic context and avoids potential pitfalls of user-defined summary statistics. We find the method is robust to a variety of demographic misspecifications using simulated data. Applied to human genotype data from Cabo Verde, we localize a known adaptive locus to a single narrow region compared with multiple or long windows obtained using two other ancestry-based methods.
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spelling pubmed-101166062023-04-21 Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes Hamid, Iman Korunes, Katharine L Schrider, Daniel R Goldberg, Amy Mol Biol Evol Methods Gene flow between previously differentiated populations during the founding of an admixed or hybrid population has the potential to introduce adaptive alleles into the new population. If the adaptive allele is common in one source population, but not the other, then as the adaptive allele rises in frequency in the admixed population, genetic ancestry from the source containing the adaptive allele will increase nearby as well. Patterns of genetic ancestry have therefore been used to identify post-admixture positive selection in humans and other animals, including examples in immunity, metabolism, and animal coloration. A common method identifies regions of the genome that have local ancestry “outliers” compared with the distribution across the rest of the genome, considering each locus independently. However, we lack theoretical models for expected distributions of ancestry under various demographic scenarios, resulting in potential false positives and false negatives. Further, ancestry patterns between distant sites are often not independent. As a result, current methods tend to infer wide genomic regions containing many genes as under selection, limiting biological interpretation. Instead, we develop a deep learning object detection method applied to images generated from local ancestry-painted genomes. This approach preserves information from the surrounding genomic context and avoids potential pitfalls of user-defined summary statistics. We find the method is robust to a variety of demographic misspecifications using simulated data. Applied to human genotype data from Cabo Verde, we localize a known adaptive locus to a single narrow region compared with multiple or long windows obtained using two other ancestry-based methods. Oxford University Press 2023-03-22 /pmc/articles/PMC10116606/ /pubmed/36947126 http://dx.doi.org/10.1093/molbev/msad074 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Methods
Hamid, Iman
Korunes, Katharine L
Schrider, Daniel R
Goldberg, Amy
Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes
title Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes
title_full Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes
title_fullStr Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes
title_full_unstemmed Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes
title_short Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes
title_sort localizing post-admixture adaptive variants with object detection on ancestry-painted chromosomes
topic Methods
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116606/
https://www.ncbi.nlm.nih.gov/pubmed/36947126
http://dx.doi.org/10.1093/molbev/msad074
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