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Current Bioinformatics

Editor-in-Chief

ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

SNP-based Computational Analysis Reveals Recombination-associated Genome Evolution in Humans

Author(s): Qiguo Zhang and Guoqing Liu*

Volume 18, Issue 2, 2023

Published on: 20 January, 2023

Page: [192 - 204] Pages: 13

DOI: 10.2174/1574893618666221226142329

Price: $65

Abstract

Background: Meiotic recombination is an important source of genetic variation, but how recombination shapes the genome is not clearly understood yet.

Objective: Here, we investigate the roles of recombination on human genome evolution from two aspects: How does recombination shape single nucleotide polymorphism (SNP)-related genomic variation features? Whether recombination drives genome evolution through a neighbor-dependent mutational bias?

Methods: We analyzed the relationship of recombination rate with mutational bias and selection effect at SNP sites derived from the 1000 Genomes Project.

Results: Our results show that SNP density, Ts/Tv, nucleotide diversity, and Tajima's D were positively correlated with the recombination rate, while Ka/Ks were negatively correlated with the recombination rate. Moreover, compared with non-coding regions, gene exonic regions have lower nucleotide diversity but higher Tajima's D, suggesting that coding regions are subject to stronger negative selection but have fewer rare alleles. Gene set enrichment analysis of the protein-coding genes with extreme Ka/Ks ratio implies that under the effect of high recombination rates, the genes involved in the cell cycle, RNA processing, and oocyte meiosis are subject to strong negative selection. Our data also support S (G or C) > W (A or T) mutational bias and W>S fixation bias in high recombination regions. In addition, the neighbor-dependent mutational bias was found to be stronger at high recombination regions.

Conclusion: Our data suggest that genetic variation patterns, particularly the neighbor-dependent mutational bias at SNP sites in the human genome, are mediated by recombination.

Keywords: Meiotic recombination, gene conversion, genetic diversity, DSB, neighbor-dependent mutational bias, recombination rate.

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[1]
Neupane S, Xu S. Adaptive divergence of meiotic recombination rate in ecological speciation. Genome Biol Evol 2020; 12(10): 1869-81.
[http://dx.doi.org/10.1093/gbe/evaa182] [PMID: 32857858]
[2]
Finsterbusch F, Ravindranathan R, Dereli I, Stanzione M, Tränkner D, Tóth A. Alignment of homologous chromosomes and effective repair of programmed DNA double-strand breaks during mouse meiosis require the minichromosome maintenance domain containing 2 (MCMDC2) protein. PLoS Genet 2016; 12(10): e1006393.
[http://dx.doi.org/10.1371/journal.pgen.1006393] [PMID: 27760146]
[3]
Lange J, Yamada S, Tischfield SE, et al. The landscape of mouse meiotic double-strand break formation, processing, and repair. Cell 2016; 167(3): 695-708.e16.
[http://dx.doi.org/10.1016/j.cell.2016.09.035] [PMID: 27745971]
[4]
Xu Y, Greenberg RA, Schonbrunn E, Wang PJ. Meiosis-specific proteins MEIOB and SPATA22 cooperatively associate with the single-stranded DNA-binding replication protein A complex and DNA double-strand breaks. Biol Reprod 2017; 96(5): 1096-104.
[http://dx.doi.org/10.1093/biolre/iox040] [PMID: 28453612]
[5]
Grelon M. Meiotic recombination mechanisms. C R Biol 2016; 339(7-8): 247-51.
[http://dx.doi.org/10.1016/j.crvi.2016.04.003] [PMID: 27180110]
[6]
Lam I, Keeney S. Mechanism and regulation of meiotic recombination initiation. Cold Spring Harb Perspect Biol 2015; 7(1): a016634.
[http://dx.doi.org/10.1101/cshperspect.a016634] [PMID: 25324213]
[7]
Hernández-López D, Geisinger A, Trovero MF, et al. Familial primary ovarian insufficiency associated with an SYCE1 point mutation: Defective meiosis elucidated in humanized mice. Mol Hum Reprod 2020; 26(7): 485-97.
[http://dx.doi.org/10.1093/molehr/gaaa032] [PMID: 32402064]
[8]
Alves I, Houle A A, Hussin J G, et al. The impact of recombination on human mutation load and disease. Philos Trans R Soc Lond B Biol Sci 2017; 372(1736): 20160465.
[http://dx.doi.org/10.1098/rstb.2016.0465]
[9]
Fan S, Jiao Y, Khan R, et al. Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans. Am J Hum Genet 2021; 108(2): 324-36.
[http://dx.doi.org/10.1016/j.ajhg.2021.01.010] [PMID: 33508233]
[10]
Galtier N, Piganeau G, Mouchiroud D, Duret L. GC-content evolution in mammalian genomes: The biased gene conversion hypothesis. Genetics 2001; 159(2): 907-11.
[http://dx.doi.org/10.1093/genetics/159.2.907] [PMID: 11693127]
[11]
Duret L, Arndt PF. The impact of recombination on nucleotide substitutions in the human genome. PLoS Genet 2008; 4(5): e1000071.
[http://dx.doi.org/10.1371/journal.pgen.1000071] [PMID: 18464896]
[12]
Weber CC, Boussau B, Romiguier J, Jarvis ED, Ellegren H. Evidence for GC-biased gene conversion as a driver of between-lineage differences in avian base composition. Genome Biol 2014; 15(12): 549-65.
[http://dx.doi.org/10.1186/s13059-014-0549-1] [PMID: 25496599]
[13]
Booker TR, Ness RW, Keightley PD. The recombination landscape in wild house mice inferred using population genomic data. Genetics 2017; 207(1): 297-309.
[http://dx.doi.org/10.1534/genetics.117.300063] [PMID: 28751421]
[14]
Hill WG, Robertson A. The effect of linkage on limits to artificial selection. Genet Res 1966; 8(3): 269-94.
[http://dx.doi.org/10.1017/S0016672300010156] [PMID: 5980116]
[15]
Silva KJ, Guimarães CT, Guilhen JHS, et al. High‐density SNP‐based genetic diversity and heterotic patterns of tropical maize breeding lines. Crop Sci 2020; 60(2): 779-87.
[http://dx.doi.org/10.1002/csc2.20018]
[16]
Berdan EL, Blanckaert A, Butlin RK, Bank C. Deleterious mutation accumulation and the long-term fate of chromosomal inversions. PLoS Genet 2021; 17(3): e1009411.
[http://dx.doi.org/10.1371/journal.pgen.1009411] [PMID: 33661924]
[17]
Cutter AD, Moses AM. Polymorphism, divergence, and the role of recombination in Saccharomyces cerevisiae genome evolution. Mol Biol Evol 2011; 28(5): 1745-54.
[http://dx.doi.org/10.1093/molbev/msq356] [PMID: 21199893]
[18]
Langley CH, Stevens K, Cardeno C, et al. Genomic variation in natural populations of Drosophila melanogaster. Genetics 2012; 192(2): 533-98.
[http://dx.doi.org/10.1534/genetics.112.142018] [PMID: 22673804]
[19]
Andersen EC, Gerke JP, Shapiro JA, et al. Chromosome-scale selective sweeps shape caenorhabditis elegans genomic diversity. Nat Genet 2012; 44(3): 285-90.
[http://dx.doi.org/10.1038/ng.1050] [PMID: 22286215]
[20]
Lercher MJ, Hurst LD. Human SNP variability and mutation rate are higher in regions of high recombination. Trends Genet 2002; 18(7): 337-40.
[http://dx.doi.org/10.1016/S0168-9525(02)02669-0] [PMID: 12127766]
[21]
Lohmueller KE, Albrechtsen A, Li Y, et al. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome. PLoS Genet 2011; 7(10): e1002326.
[http://dx.doi.org/10.1371/journal.pgen.1002326] [PMID: 22022285]
[22]
Cutter AD, Payseur BA. Genomic signatures of selection at linked sites: Unifying the disparity among species. Nat Rev Genet 2013; 14(4): 262-74.
[http://dx.doi.org/10.1038/nrg3425] [PMID: 23478346]
[23]
Charlesworth B. The effects of deleterious mutations on evolution at linked sites. Genetics 2012; 190(1): 5-22.
[http://dx.doi.org/10.1534/genetics.111.134288] [PMID: 22219506]
[24]
Stephan W. Genetic hitchhiking versus background selection: The controversy and its implications. Philos Trans R Soc Lond B Biol Sci 2010; 365(1544): 1245-53.
[http://dx.doi.org/10.1098/rstb.2009.0278] [PMID: 20308100]
[25]
Webster MT, Hurst LD. Direct and indirect consequences of meiotic recombination: Implications for genome evolution. Trends Genet 2012; 28(3): 101-9.
[http://dx.doi.org/10.1016/j.tig.2011.11.002] [PMID: 22154475]
[26]
Charlesworth B, Betancourt AJ, Kaiser VB, Gordo I. Genetic recombination and molecular evolution. Cold Spring Harb Symp Quant Biol 2009; 74(0): 177-86.
[http://dx.doi.org/10.1101/sqb.2009.74.015] [PMID: 19734202]
[27]
McVean GAT, Charlesworth B. The effects of hill-robertson interference between weakly selected mutations on patterns of molecular evolution and variation. Genetics 2000; 155(2): 929-44.
[http://dx.doi.org/10.1093/genetics/155.2.929] [PMID: 10835411]
[28]
Comeron JM, Kreitman M. The correlation between intron length and recombination in Drosophila. Dynamic equilibrium between mutational and selective forces. Genetics 2000; 156(3): 1175-90.
[http://dx.doi.org/10.1093/genetics/156.3.1175] [PMID: 11063693]
[29]
Comeron JM. Background selection as baseline for nucleotide variation across the Drosophila genome. PLoS Genet 2014; 10(6): e1004434.
[http://dx.doi.org/10.1371/journal.pgen.1004434] [PMID: 24968283]
[30]
Andolfatto P. Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome. Genome earch 2008; 17(12): 1755-62.
[31]
Hernandez RD, Kelley JL, Elyashiv E, et al. Classic selective sweeps were rare in recent human evolution. Science 2011; 331(6019): 920-4.
[http://dx.doi.org/10.1126/science.1198878] [PMID: 21330547]
[32]
Reed FA, Akey JM, Aquadro CF. Fitting background-selection predictions to levels of nucleotide variation and divergence along the human autosomes. Genome Res 2005; 15(9): 1211-21.
[http://dx.doi.org/10.1101/gr.3413205] [PMID: 16140989]
[33]
Katzman S, Capra JA, Haussler D, Pollard KS. Ongoing GC-biased evolution is widespread in the human genome and enriched near recombination hot spots. Genome Biol Evol 2011; 3(1): 614-26.
[http://dx.doi.org/10.1093/gbe/evr058] [PMID: 21697099]
[34]
Necşulea A, Popa A, Cooper DN, et al. Meiotic recombination favors the spreading of deleterious mutations in human populations. Hum Mutat 2011; 32(2): 198-206.
[http://dx.doi.org/10.1002/humu.21407] [PMID: 21120948]
[35]
Arbeithuber B, Betancourt AJ, Ebner T, Tiemann-Boege I. Crossovers are associated with mutation and biased gene conversion at recombination hotspots. Proc Natl Acad Sci 2015; 112(7): 2109-14.
[http://dx.doi.org/10.1073/pnas.1416622112] [PMID: 25646453]
[36]
Hernandez RD, Williamson SH, Bustamante CD. Context dependence, ancestral misidentification, and spurious signatures of natural selection. Mol Biol Evol 2007; 24(8): 1792-800.
[http://dx.doi.org/10.1093/molbev/msm108] [PMID: 17545186]
[37]
Hwang DG, Green P. Bayesian markov chain monte carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution. Proc Natl Acad Sci 2004; 101(39): 13994-4001.
[http://dx.doi.org/10.1073/pnas.0404142101] [PMID: 15292512]
[38]
Arndt PF, Burge CB, Hwa T. DNA sequence evolution with neighbor-dependent mutation. J Comput Biol 2003; 10(3-4): 313-22.
[http://dx.doi.org/10.1089/10665270360688039] [PMID: 12935330]
[39]
Nevarez PA, DeBoever CM, Freeland BJ, Quitt MA, Bush EC. Context dependent substitution biases vary within the human genome. BMC Bioinformatics 2010; 11(1): 462.
[http://dx.doi.org/10.1186/1471-2105-11-462] [PMID: 20843365]
[40]
Liu G, Li H. The correlation between recombination rate and dinucleotide bias in Drosophila melanogaster. J Mol Evol 2008; 67(4): 358-67.
[http://dx.doi.org/10.1007/s00239-008-9150-0] [PMID: 18797953]
[41]
Danecek P, Auton A, Abecasis G, et al. The variant call format and VCFtools. Bioinformatics 2011; 27(15): 2156-8.
[http://dx.doi.org/10.1093/bioinformatics/btr330] [PMID: 21653522]
[42]
Bhérer C, Campbell CL, Auton A. Refined genetic maps reveal sexual dimorphism in human meiotic recombination at multiple scales. Nat Commun 2017; 8(1): 14994.
[http://dx.doi.org/10.1038/ncomms14994] [PMID: 28440270]
[43]
Cingolani P, Platts A, Wang LL, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff. Fly 2012; 6(2): 80-92.
[http://dx.doi.org/10.4161/fly.19695] [PMID: 22728672]
[44]
Wang D, Zhang Y, Zhang Z, Zhu J, Yu J. KaKs_calculator 2.0: A toolkit incorporating gamma-series methods and sliding window strategies. Gen Prote Bioinform 2010; 8(1): 77-80.
[http://dx.doi.org/10.1016/S1672-0229(10)60008-3] [PMID: 20451164]
[45]
Wang DP, Wan HL, Zhang S, Yu J. γ-MYN: A new algorithm for estimating Ka and Ks with consideration of variable substitution rates. Biol Direct 2009; 4(1): 20-38.
[http://dx.doi.org/10.1186/1745-6150-4-20] [PMID: 19531225]
[46]
Wang D, Zhang S, He F, Zhu J, Hu S, Yu J. How do variable substitution rates influence Ka and Ks calculations? Genomics Proteomics Bioinformatics 2009; 7(3): 116-27.
[http://dx.doi.org/10.1016/S1672-0229(08)60040-6] [PMID: 19944384]
[47]
Nei M, Gojobori T. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 1986; 3(5): 418-26.
[PMID: 3444411]
[48]
Li WH, Wu CI, Luo CC. A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol 1985; 2(2): 150-74.
[PMID: 3916709]
[49]
Tzeng YH, Pan R, Li WH. Comparison of three methods for estimating rates of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 2004; 21(12): 2290-8.
[http://dx.doi.org/10.1093/molbev/msh242] [PMID: 15329386]
[50]
Li WH. Unbiased estimation of the rates of synonymous and nonsynonymous substitution. J Mol Evol 1993; 36(1): 96-9.
[http://dx.doi.org/10.1007/BF02407308] [PMID: 8433381]
[51]
Yu G, Wang LG, Han Y, He QY. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 2012; 16(5): 284-7.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[52]
Quinlan AR, Hall IM. BEDTools: A flexible suite of utilities for comparing genomic features. Bioinformatics 2010; 26(6): 841-2.
[http://dx.doi.org/10.1093/bioinformatics/btq033] [PMID: 20110278]
[53]
Zhao Z, Boerwinkle E. Neighboring-nucleotide effects on single nucleotide polymorphisms: A study of 2.6 million polymorphisms across the human genome. Genome Res 2002; 12(11): 1679-86.
[http://dx.doi.org/10.1101/gr.287302] [PMID: 12421754]
[54]
Krawczak M, Ball EV, Cooper DN. Neighboring-nucleotide effects on the rates of germ-line single-base-pair substitution in human genes. Am J Hum Genet 1998; 63(2): 474-88.
[http://dx.doi.org/10.1086/301965] [PMID: 9683596]

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