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

Authors :
Chenlu Di
Jesus Murga Moreno
Diego F Salazar-Tortosa
M Elise Lauterbur
David Enard
Source :
eLife, Vol 10 (2021)
Publication Year :
2021
Publisher :
eLife Sciences Publications Ltd, 2021.

Abstract

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.

Details

Language :
English
ISSN :
2050084X
Volume :
10
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.5db49e16e08f432382eef960a9a04d08
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.69026