Evolutionary and Functional Impact of Common Polymorphic Inversions in the Human Genome

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Sep 19

PMID 31530810

Citations 32

Authors

Carla Giner-Delgado

Sergi Villatoro

Jon Lerga-Jaso

Magdalena Gaya-Vidal

Meritxell Oliva

David Castellano

Lorena Pantano

Barbara D Bitarello

David Izquierdo

Isaac Noguera

Inigo Olalde

Alejandra Delprat

Antoine Blancher

Carles Lalueza-Fox

Tonu Esko

Paul F OReilly

Aida M Andres

Luca Ferretti

Marta Puig

Mario Caceres

Affiliations

Soon will be listed here.

Abstract

Inversions are one type of structural variants linked to phenotypic differences and adaptation in multiple organisms. However, there is still very little information about polymorphic inversions in the human genome due to the difficulty of their detection. Here, we develop a new high-throughput genotyping method based on probe hybridization and amplification, and we perform a complete study of 45 common human inversions of 0.1-415 kb. Most inversions promoted by homologous recombination occur recurrently in humans and great apes and they are not tagged by SNPs. Furthermore, there is an enrichment of inversions showing signatures of positive or balancing selection, diverse functional effects, such as gene disruption and gene-expression changes, or association with phenotypic traits. Therefore, our results indicate that the genome is more dynamic than previously thought and that human inversions have important functional and evolutionary consequences, making possible to determine for the first time their contribution to complex traits.

Citing Articles

Inversions encounter relaxed genetic constraints and balance birth and death of TPS genes in Curcuma.

Liao X, Xie D, Bao T, Hou M, Li C, Nie B Nat Commun. 2024; 15(1):9349.

PMID: 39472560 PMC: 11522489. DOI: 10.1038/s41467-024-53719-y.

Machine Learning Reveals the Diversity of Human 3D Chromatin Contact Patterns.

Gilbertson E, Brand C, McArthur E, Rinker D, Kuang S, Pollard K Mol Biol Evol. 2024; 41(10).

PMID: 39404010 PMC: 11523124. DOI: 10.1093/molbev/msae209.

The evolutionary fate of Neanderthal DNA in 30,780 admixed genomes with recent African-like ancestry.

Pfennig A, Lachance J bioRxiv. 2024; .

PMID: 39091830 PMC: 11291122. DOI: 10.1101/2024.07.25.605203.

Unraveling the complex role of MAPT-containing H1 and H2 haplotypes in neurodegenerative diseases.

Pedicone C, Weitzman S, Renton A, Goate A Mol Neurodegener. 2024; 19(1):43.

PMID: 38812061 PMC: 11138017. DOI: 10.1186/s13024-024-00731-x.

Out with the old, in with the new: Meiotic driving of sex chromosome evolution.

Swanepoel C, Mueller J Semin Cell Dev Biol. 2024; 163:14-21.

PMID: 38664120 PMC: 11351068. DOI: 10.1016/j.semcdb.2024.04.004.

References

Lakich D, Kazazian Jr H, Antonarakis S, Gitschier J . Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nat Genet. 1993; 5(3):236-41. DOI: 10.1038/ng1193-236. View

Battle A, Brown C, Engelhardt B, Montgomery S . Genetic effects on gene expression across human tissues. Nature. 2017; 550(7675):204-213. PMC: 5776756. DOI: 10.1038/nature24277. View

Kidd J, Cooper G, Donahue W, Hayden H, Sampas N, Graves T . Mapping and sequencing of structural variation from eight human genomes. Nature. 2008; 453(7191):56-64. PMC: 2424287. DOI: 10.1038/nature06862. View

Li B, Dewey C . RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics. 2011; 12:323. PMC: 3163565. DOI: 10.1186/1471-2105-12-323. View

Gonzalez J, Caceres A, Esko T, Cusco I, Puig M, Esnaola M . A common 16p11.2 inversion underlies the joint susceptibility to asthma and obesity. Am J Hum Genet. 2014; 94(3):361-72. PMC: 3951940. DOI: 10.1016/j.ajhg.2014.01.015. View

Aguado C, Gaya-Vidal M, Villatoro S, Oliva M, Izquierdo D, Giner-Delgado C . Validation and genotyping of multiple human polymorphic inversions mediated by inverted repeats reveals a high degree of recurrence. PLoS Genet. 2014; 10(3):e1004208. PMC: 3961182. DOI: 10.1371/journal.pgen.1004208. View

Horton R, Gibson R, Coggill P, Miretti M, Allcock R, Almeida J . Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project. Immunogenetics. 2008; 60(1):1-18. PMC: 2206249. DOI: 10.1007/s00251-007-0262-2. View

Webb A, Miller B, Bonasera S, Boxer A, Karydas A, Wilhelmsen K . Role of the tau gene region chromosome inversion in progressive supranuclear palsy, corticobasal degeneration, and related disorders. Arch Neurol. 2008; 65(11):1473-8. PMC: 2680206. DOI: 10.1001/archneur.65.11.1473. View

Eichler E, Flint J, Gibson G, Kong A, Leal S, Moore J . Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet. 2010; 11(6):446-50. PMC: 2942068. DOI: 10.1038/nrg2809. View

10.

Bandelt H, Forster P, Rohl A . Median-joining networks for inferring intraspecific phylogenies. Mol Biol Evol. 1999; 16(1):37-48. DOI: 10.1093/oxfordjournals.molbev.a026036. View

11.

Tielsch J, Sommer A, Katz J, Royall R, Quigley H, Javitt J . Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey. JAMA. 1991; 266(3):369-74. View

12.

Handsaker R, Van Doren V, Berman J, Genovese G, Kashin S, Boettger L . Large multiallelic copy number variations in humans. Nat Genet. 2015; 47(3):296-303. PMC: 4405206. DOI: 10.1038/ng.3200. View

13.

Abecasis G, Auton A, Brooks L, DePristo M, Durbin R, Handsaker R . An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491(7422):56-65. PMC: 3498066. DOI: 10.1038/nature11632. View

14.

Li M, Liu Z, Wang P, Wong M, Nelson M, Kocher J . GWASdb v2: an update database for human genetic variants identified by genome-wide association studies. Nucleic Acids Res. 2015; 44(D1):D869-76. PMC: 4702921. DOI: 10.1093/nar/gkv1317. View

15.

Ferretti L, Klassmann A, Raineri E, Ramos-Onsins S, Wiehe T, Achaz G . The neutral frequency spectrum of linked sites. Theor Popul Biol. 2018; 123:70-79. DOI: 10.1016/j.tpb.2018.06.001. View

16.

Huddleston J, Chaisson M, Steinberg K, Warren W, Hoekzema K, Gordon D . Discovery and genotyping of structural variation from long-read haploid genome sequence data. Genome Res. 2016; 27(5):677-685. PMC: 5411763. DOI: 10.1101/gr.214007.116. View

17.

Repping S, van Daalen S, Brown L, Korver C, Lange J, Marszalek J . High mutation rates have driven extensive structural polymorphism among human Y chromosomes. Nat Genet. 2006; 38(4):463-7. DOI: 10.1038/ng1754. View

18.

Sun B, Maranville J, Peters J, Stacey D, Staley J, Blackshaw J . Genomic atlas of the human plasma proteome. Nature. 2018; 558(7708):73-79. PMC: 6697541. DOI: 10.1038/s41586-018-0175-2. View

19.

Sudmant P, Rausch T, Gardner E, Handsaker R, Abyzov A, Huddleston J . An integrated map of structural variation in 2,504 human genomes. Nature. 2015; 526(7571):75-81. PMC: 4617611. DOI: 10.1038/nature15394. View

20.

Kirkpatrick M . How and why chromosome inversions evolve. PLoS Biol. 2010; 8(9). PMC: 2946949. DOI: 10.1371/journal.pbio.1000501. View