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Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants

Advances in genome sequencing have improved our understanding of the genetic basis of human diseases, and thousands of human genes have been associated with different diseases. Recent genomic adaptation at disease genes has not been well characterized. Here, we compare the rate of strong recent adap...

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Autores principales: Di, Chenlu, Murga Moreno, Jesus, Salazar-Tortosa, Diego F, Lauterbur, M Elise, Enard, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526059/
https://www.ncbi.nlm.nih.gov/pubmed/34636724
http://dx.doi.org/10.7554/eLife.69026
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author Di, Chenlu
Murga Moreno, Jesus
Salazar-Tortosa, Diego F
Lauterbur, M Elise
Enard, David
author_facet Di, Chenlu
Murga Moreno, Jesus
Salazar-Tortosa, Diego F
Lauterbur, M Elise
Enard, David
author_sort Di, Chenlu
collection PubMed
description Advances in genome sequencing have improved our understanding of the genetic basis of human diseases, and thousands of human genes have been associated with different diseases. Recent genomic adaptation at disease genes has not been well characterized. Here, we compare the rate of strong recent adaptation in the form of selective sweeps between mendelian, non-infectious disease genes and non-disease genes across distinct human populations from the 1000 Genomes Project. We find that mendelian disease genes have experienced far less selective sweeps compared to non-disease genes especially in Africa. Investigating further the possible causes of the sweep deficit at disease genes, we find that this deficit is very strong at disease genes with both low recombination rates and with high numbers of associated disease variants, but is almost non-existent at disease genes with higher recombination rates or lower numbers of associated disease variants. Because segregating recessive deleterious variants have the ability to interfere with adaptive ones, these observations strongly suggest that adaptation has been slowed down by the presence of interfering recessive deleterious variants at disease genes. These results suggest that disease genes suffer from a transient inability to adapt as fast as the rest of the genome.
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spelling pubmed-85260592021-10-21 Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants Di, Chenlu Murga Moreno, Jesus Salazar-Tortosa, Diego F Lauterbur, M Elise Enard, David eLife Evolutionary Biology Advances in genome sequencing have improved our understanding of the genetic basis of human diseases, and thousands of human genes have been associated with different diseases. Recent genomic adaptation at disease genes has not been well characterized. Here, we compare the rate of strong recent adaptation in the form of selective sweeps between mendelian, non-infectious disease genes and non-disease genes across distinct human populations from the 1000 Genomes Project. We find that mendelian disease genes have experienced far less selective sweeps compared to non-disease genes especially in Africa. Investigating further the possible causes of the sweep deficit at disease genes, we find that this deficit is very strong at disease genes with both low recombination rates and with high numbers of associated disease variants, but is almost non-existent at disease genes with higher recombination rates or lower numbers of associated disease variants. Because segregating recessive deleterious variants have the ability to interfere with adaptive ones, these observations strongly suggest that adaptation has been slowed down by the presence of interfering recessive deleterious variants at disease genes. These results suggest that disease genes suffer from a transient inability to adapt as fast as the rest of the genome. eLife Sciences Publications, Ltd 2021-10-12 /pmc/articles/PMC8526059/ /pubmed/34636724 http://dx.doi.org/10.7554/eLife.69026 Text en © 2021, Di et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Evolutionary Biology
Di, Chenlu
Murga Moreno, Jesus
Salazar-Tortosa, Diego F
Lauterbur, M Elise
Enard, David
Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants
title Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants
title_full Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants
title_fullStr Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants
title_full_unstemmed Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants
title_short Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants
title_sort decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants
topic Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526059/
https://www.ncbi.nlm.nih.gov/pubmed/34636724
http://dx.doi.org/10.7554/eLife.69026
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