Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants
Di, Chenlu (University of Arizona. Department of Ecology and Evolutionary Biology)
Murga-Moreno, Jesus (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Salazar-Tortosa, Diego F (University of Arizona. Department of Ecology and Evolutionary Biology)
Lauterbur, M. Elise (University of Arizona. Department of Ecology and Evolutionary Biology)
Enard, David (University of Arizona. Department of Ecology and Evolutionary Biology)

Data:	2021
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Disease genes ; Adaptive evolution ; Genetic interference ; Bottlenecks ; Selective sweeps ; Human
Publicat a:	eLife, Vol. 10 (October 2021) , art. e69026, ISSN 2050-084X

DOI: 10.7554/eLife.69026
PMID: 34636724

27 p, 1.5 MB

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