Abstract
Background
Long interspersed element-1 (LINE-1 or L1) is the most abundant retrotransposons in the primate genome. They have approximately 520,000 copies and make up ~ 17% of the primate genome. Full-length L1s can mobilize to a new genomic location using their enzymatic machinery. Gorilla is the second closest species to humans after the chimpanzee, and human-gorilla split 7–12 million years ago. The gorilla genome provides an opportunity to explore primate origins and evolution.
Objective
L1s have contributed to genome diversity and variations during primate evolution. This study aimed to identify gorilla-specific L1s using a more recent version of the gorilla reference genome (Mar. 2016 GSMRT3/gorGor5).
Methods
We collected gorilla-specific L1 candidates through computational analysis and manual inspection. L1Xplorer was used to identify whether full-length gorilla-specific L1s were intact. In addition, to determine the level of sequence conservation between intact fulllength gorilla-specific L1s, two ORFs of intact L1s were aligned with the L1PA2 consensus sequence.
Results
2002 gorilla-specific L1 candidates were identified through computational analysis. Among them, we manually inspected 1,883 gorilla-specific L1s, among which most of them belong to the L1PA2 subfamily and 12 were intact L1s that could influence genomic variations in the gorilla genome. Interestingly, the 12 intact full-length gorilla-specific L1s have 14 highly conserved nonsynonymous mutations, including 6 mutations and 8 mutations in ORF1 and ORF2, respectively. In comparison to the intact full-length chimpanzee-specific L1s and human-specific hot-L1s, two of these in ORF1 (L256F and E293G) were shown as gorilla-specific nonsynonymous mutations.
Conclusion
The gorilla-specific L1s may have had significantly affected the gorilla genome to compose a genome different form that of other primates during primate evolution.
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References
Beck CR, Collier P, Macfarlane C, Malig M, Kidd JM, Eichler EE, Badge RM, Moran JV (2010) LINE-1 retrotransposition activity in human genomes. Cell 141:1159–1170
Beck CR, Garcia-Perez JL, Badge RM, Moran JV (2011) LINE-1 elements in structural variation and disease. Annu Rev Genomics Hum Genet 12:187–215
Belancio VP, Hedges DJ, Deininger P (2008) Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res 18:343–358
Boissinot S, Entezam A, Furano AV (2001) Selection against deleterious LINE-1-containing loci in the human lineage. Mol Biol Evol 18:926–935
Brouha B, Schustak J, Badge RM, Lutz-Prigge S, Farley AH, Moran JV, Kazazian HH Jr (2003) Hot L1s account for the bulk of retrotransposition in the human population. Proc Natl Acad Sci USA 100:5280–5285
Burwinkel B, Kilimann MW (1998) Unequal homologous recombination between LINE-1 elements as a mutational mechanism in human genetic disease. J Mol Biol 277:513–517
Chen JM, Stenson PD, Cooper DN, Ferec C (2005) A systematic analysis of LINE-1 endonuclease-dependent retrotranspositional events causing human genetic disease. Hum Genet 117:411–427
Chimpanzee S, Analysis C (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437:69–87
Cordaux R, Batzer MA (2009) The impact of retrotransposons on human genome evolution. Nat Rev Genet 10:691–703
Currall BB, Chiang C, Talkowski ME, Morton CC (2013) Mechanisms for structural variation in the human genome. Curr Genet Med Rep 1:81–90
Deininger PL, Moran JV, Batzer MA, Kazazian HH Jr (2003) Mobile elements and mammalian genome evolution. Curr Opin Genet Dev 13:651–658
Dombroski BA, Mathias SL, Nanthakumar E, Scott AF, Kazazian HH Jr (1991) Isolation of an active human transposable element. Science 254:1805–1808
Ewing AD, Kazazian HH Jr (2010) High-throughput sequencing reveals extensive variation in human-specific L1 content in individual human genomes. Genome Res 20:1262–1270
Ewing AD, Kazazian HH Jr (2011) Whole-genome resequencing allows detection of many rare LINE-1 insertion alleles in humans. Genome Res 21:985–990
Fanning T, Singer M (1987) The LINE-1 DNA sequences in four mammalian orders predict proteins that conserve homologies to retrovirus proteins. Nucleic Acids Res 15:2251–2260
Farley AH, Luning Prak ET, Kazazian HH Jr (2004) More active human L1 retrotransposons produce longer insertions. Nucleic Acids Res 32:502–510
Finstermeier K, Zinner D, Brameier M, Meyer M, Kreuz E, Hofreiter M, Roos C (2013) A mitogenomic phylogeny of living primates. PLoS ONE 8:e69504
Gibbs RA, Rogers J (2012) Genomics: gorilla gorilla gorilla. Nature 483:164–165
Gilbert N, Lutz S, Morrish TA, Moran JV (2005) Multiple fates of L1 retrotransposition intermediates in cultured human cells. Mol Cell Biol 25:7780–7795
Gokcumen O, Tischler V, Tica J, Zhu Q, Iskow RC, Lee E, Fritz MH, Langdon A, Stutz AM, Pavlidis P et al (2013) Primate genome architecture influences structural variation mechanisms and functional consequences. Proc Natl Acad Sci USA 110:15764–15769
Gordon D, Huddleston J, Chaisson MJ, Hill CM, Kronenberg ZN, Munson KM, Malig M, Raja A, Fiddes I, Hillier LW et al (2016) Long-read sequence assembly of the gorilla genome. Science 352:aae0344
Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98
Han K, Sen SK, Wang J, Callinan PA, Lee J, Cordaux R, Liang P, Batzer MA (2005) Genomic rearrangements by LINE-1 insertion-mediated deletion in the human and chimpanzee lineages. Nucleic Acids Res 33:4040–4052
Han K, Lee J, Meyer TJ, Remedios P, Goodwin L, Batzer MA (2008) L1 recombination-associated deletions generate human genomic variation. Proc Matl Acad Sci USA 105:19366–19371
Hata K, Sakaki Y (1997) Identification of critical CpG sites for repression of L1 transcription by DNA methylation. Gene 189:227–234
Helman E, Lawrence MS, Stewart C, Sougnez C, Getz G, Meyerson M (2014) Somatic retrotransposition in human cancer revealed by whole-genome and exome sequencing. Genome Res 24:1053–1063
Kaer K, Branovets J, Hallikma A, Nigumann P, Speek M (2011) Intronic L1 retrotransposons and nested genes cause transcriptional interference by inducing intron retention, exonization and cryptic polyadenylation. PLoS ONE 6:e26099
Kazazian HH Jr (2004) Mobile elements: drivers of genome evolution. Science 303:1626–1632
Kazazian HH Jr, Moran JV (1998) The impact of L1 retrotransposons on the human genome. Nat Genet 19:19–24
Khan H, Smit A, Boissinot S (2006) Molecular evolution and tempo of amplification of human LINE-1 retrotransposons since the origin of primates. Genome Res 16:78–87
Kim S, Shin W, Lee YM, Mun S, Han K (2020) Differential expressions of L1-chimeric transcripts in normal and matched-cancer tissues. Anal Biochem 600:113769
Kolosha VO, Martin SL (2003) High-affinity, non-sequence-specific RNA binding by the open reading frame 1 (ORF1) protein from long interspersed nuclear element 1 (LINE-1). J Biol Chem 278:8112–8117
Konkel MK, Walker JA, Batzer MA (2010) LINEs and SINEs of primate evolution. Evol Anthropol 19:236–249
Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921
Lee J, Cordaux R, Han K, Wang J, Hedges DJ, Liang P, Batzer MA (2007) Different evolutionary fates of recently integrated human and chimpanzee LINE-1 retrotransposons. Gene 390:18–27
Lee HE, Eo J, Kim HS (2015) Composition and evolutionary importance of transposable elements in humans and primates. Genes Genomics 37:135–140
Lee S, Tang W, Liang P, Han K (2019) A comprehensive analysis of chimpanzee (Pan troglodytes)-specific LINE-1 retrotransposons. Gene 693:46–51
Lyon MF (2000) LINE-1 elements and X chromosome inactivation: a function for “junk” DNA? Proc Natl Acad Sci USA 97:6248–6249
Malik HS, Burke WD, Eickbush TH (1999) The age and evolution of non-LTR retrotransposable elements. Mol Biol Evol 16:793–805
Martin SL (2006) The ORF1 protein encoded by LINE-1: structure and function during L1 retrotransposition. J Biomed Biotechnol 2006:45621
Mathias SL, Scott AF, Kazazian HH Jr, Boeke JD, Gabriel A (1991) Reverse transcriptase encoded by a human transposable element. Science 254:1808–1810
McLain AT, Carman GW, Fullerton ML, Beckstrom TO, Gensler W, Meyer TJ, Faulk C, Batzer MA (2013) Analysis of western lowland gorilla (Gorilla gorilla gorilla) specific Alu repeats. Mob DNA 4:26
Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler KW, Vogelstein B, Nakamura Y (1992) Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res 52:643–645
Morrish TA, Gilbert N, Myers JS, Vincent BJ, Stamato TD, Taccioli GE, Batzer MA, Moran JV (2002) DNA repair mediated by endonuclease-independent LINE-1 retrotransposition. Nat Genet 31:159–165
Mun S, Kim S, Lee W, Kang K, Meyer TJ, Han BG, Han K, Kim HS (2021) A study of transposable element-associated structural variations (TASVs) using a de novo-assembled Korean genome. Exp Mol Med 53:615–630
Muthukumaran R, Sangeetha B, Amutha R (2015) Conformational analysis on the wild type and mutated forms of human ORF1p: a molecular dynamics study. Mol Biosyst 11:1987–1999
Penzkofer T, Dandekar T, Zemojtel T (2005) L1Base: from functional annotation to prediction of active LINE-1 elements. Nucleic Acids Res 33:D498-500
Prufer K, Munch K, Hellmann I, Akagi K, Miller JR, Walenz B, Koren S, Sutton G, Kodira C, Winer R et al (2012) The bonobo genome compared with the chimpanzee and human genomes. Nature 486:527–531
Rajagopalan M, Balasubramanian S, Ramaswamy A (2017) Insights into the RNA binding mechanism of human L1-ORF1p: a molecular dynamics study. Mol Biosyst 13:1728–1743
Rangwala SH, Zhang L, Kazazian HH Jr (2009) Many LINE1 elements contribute to the transcriptome of human somatic cells. Genome Biol 10:R100
Rhesus Macaque Genome S, Analysis C, Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, Mardis ER, Remington KA, Strausberg RL et al (2007) Evolutionary and biomedical insights from the rhesus macaque genome. Science 316:222–234
Rogers J, Gibbs RA (2014) Comparative primate genomics: emerging patterns of genome content and dynamics. Nat Rev Genet 15:347–359
Samonte RV, Eichler EE (2002) Segmental duplications and the evolution of the primate genome. Nat Rev Genet 3:65–72
Scally A, Dutheil JY, Hillier LW, Jordan GE, Goodhead I, Herrero J, Hobolth A, Lappalainen T, Mailund T, Marques-Bonet T et al (2012) Insights into hominid evolution from the gorilla genome sequence. Nature 483:169–175
Scott EC, Gardner EJ, Masood A, Chuang NT, Vertino PM, Devine SE (2016) A hot L1 retrotransposon evades somatic repression and initiates human colorectal cancer. Genome Res 26:745–755
Sen SK, Huang CT, Han K, Batzer MA (2007) Endonuclease-independent insertion provides an alternative pathway for L1 retrotransposition in the human genome. Nucleic Acids Res 35:3741–3751
Shin W, Mun S, Kim J, Lee W, Park DG, Choi S, Lee TY, Cha S, Han K (2019) Novel discovery of LINE-1 in a Korean individual by a target enrichment method. Mol Cells 42:87–95
Smit AF (1999) Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr Opin Genet Dev 9:657–663
Sultana T, van Essen D, Siol O, Bailly-Bechet M, Philippe C, Zine El Aabidine A, Pioger L, Nigumann P, Saccani S, Andrau JC et al (2019) The landscape of L1 retrotransposons in the human genome is shaped by pre-insertion sequence biases and post-insertion selection. Mol Cell 74:555–570
Szak ST, Pickeral OK, Makalowski W, Boguski MS, Landsman D, Boeke JD (2002) Molecular archeology of L1 insertions in the human genome. Genome Biol 3:research0052
Tang W, Liang P (2019) Comparative genomics analysis reveals high levels of differential retrotransposition among primates from the hominidae and the cercopithecidae families. Genome Biol Evol 11:3309–3325
Tang W, Mun S, Joshi A, Han K, Liang P (2018) Mobile elements contribute to the uniqueness of human genome with 15,000 human-specific insertions and 14 Mbp sequence increase. DNA Res 25:521–533
Woodcock DM, Lawler CB, Linsenmeyer ME, Doherty JP, Warren WD (1997) Asymmetric methylation in the hypermethylated CpG promoter region of the human L1 retrotransposon. J Biol Chem 272:7810–7816
Xing J, Zhang Y, Han K, Salem AH, Sen SK, Huff CD, Zhou Q, Kirkness EF, Levy S, Batzer MA et al (2009) Mobile elements create structural variation: analysis of a complete human genome. Genome Res 19:1516–1526
Zingler N, Willhoeft U, Brose HP, Schoder V, Jahns T, Hanschmann KM, Morrish TA, Lower J, Schumann GG (2005) Analysis of 5’ junctions of human LINE-1 and Alu retrotransposons suggests an alternative model for 5’-end attachment requiring microhomology-mediated end-joining. Genome Res 15:780–789
Acknowledgements
This research was enabled in part by support provided by SHARCNET (www.sharcnet.ca) and Compute Canada (www.computecanada.ca). This research was supported by funding from Basic Science Research Capacity Enhancement Project through Korea Basic Science Institute (National research Facilities and Equipment Center) Grant by the Ministry of Education (Grant No. 2019R1A6C1010033) to K.H. and NSERC Discovery Grant (RGPIN-2017-06785) to P.L. The Department of Microbiology was supported through the Research-Focused Department Promotion Project as a part of the University Innovation Support Program for Dankook University in 2021.
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13258_2021_1146_MOESM1_ESM.pdf
Supplementary Fig. S1 Examples of removed gorilla L1 candidates. In UCSC Genome Browser, two copies of TE (red and blue boxes) were detected. However, through manual inspection, two copies of TEs were identified as one copy of TE (PDF 80 KB)
13258_2021_1146_MOESM2_ESM.pdf
Supplementary Fig. S2 Chromosomal distribution of 1,858 gorilla-specific L1s. The dark blue bars indicate the density (number of L1s/Mbp) of gorilla-specific L1s in each chromosome. The hatching blue boxes denote the density of full-length L1s. The density of unknown chromosome (25 loci) were not included (PDF 31 KB)
13258_2021_1146_MOESM3_ESM.pdf
Supplementary Fig. S3 Alignment of 12 intact full-length gorilla-specific L1s, 9 intact full-length chimpanzee-specific L1s, and 90 human hot-L1s with L1PA consensus sequences (ORF1). By using BioEdit program, ORF1 region of gorilla, chimpanzee, human L1s were aligned with four L1PA consensus sequences (L1PA2, L1PA3, L1PA4, and L1PA5). Yellow, blue, and green boxes denote gorilla, chimpanzee, and human L1s, respectively. Red boxes indicate missense mutations of 12 gorilla-specific intact L1s (PDF 1867 KB)
13258_2021_1146_MOESM4_ESM.pdf
Supplementary Fig. S4 Alignment of 12 intact full-length gorilla-specific L1s, 9 intact full-length chimpanzee-specific L1s, and 90 human hot-L1s with L1PA consensus sequences (ORF2). By using BioEdit program, ORF2 region of gorilla, chimpanzee, human L1s were aligned with four L1PA consensus sequences (L1PA2, L1PA3, L1PA4, and L1PA5). Yellow, blue, and green boxes denote gorilla, chimpanzee, and human L1s, respectively. Red boxes indicate missense mutations of 12 gorilla-specific intact L1s (PDF 7393 KB)
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Jeon, S., Kim, S., Oh, M.H. et al. A comprehensive analysis of gorilla-specific LINE-1 retrotransposons. Genes Genom 43, 1133–1141 (2021). https://doi.org/10.1007/s13258-021-01146-4
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DOI: https://doi.org/10.1007/s13258-021-01146-4