Somatic gene recombination in post-mitotic neurons

References

1. Naumova, O. Y., Lee, M., Rychkov, S. Y., Vlasova, N. V., and Grigorenko, E. L. (2013)
Gene expression in the human brain: the current state of the study of specificity and
spatiotemporal dynamics. Child Dev 84, 76-88
2. Colantuoni, C., Purcell, A. E., Bouton, C. M., and Pevsner, J. (2000) High throughput
analysis of gene expression in the human brain. J Neurosci Res 59, 1-10
3. Dreyer, W., Gray, W., and Hood, L. (1967) The genetic, molecular, and cellular basis of
antibody formation: some facts and a unifying hypothesis. Cold Spring Harbor Symposia
4. Dreyer, W. J., and Bennett, J. C. (1965) The molecular basis of antibody formation: a
paradox. Proc Natl Acad Sci U S A 54, 864-869
5. Hozumi, N., and Tonegawa, S. (1976) Evidence for somatic rearrangement of
immunoglobulin genes coding for variable and constant regions. Proc Natl Acad Sci U S
A 73, 3628-3632
6. Chun, J. J., Schatz, D. G., Oettinger, M. A., Jaenisch, R., and Baltimore, D. (1991) The
recombination activating gene-1 (RAG-1) transcript is present in the murine central

Downloaded from http://www.jbc.org/ by guest on July 23, 2020

nervous system. Cell 64, 189-200
7. Gao, Y., Sun, Y., Frank, K. M., Dikkes, P., Fujiwara, Y., Seidl, K. J., Sekiguchi, J. M.,
Rathbun, G. A., Swat, W., Wang, J., Bronson, R. T., Malynn, B. A., Bryans, M., Zhu, C.,
Chaudhuri, J., Davidson, L., Ferrini, R., Stamato, T., Orkin, S. H., Greenberg, M. E., and
Alt, F. W. (1998) A critical role for DNA end-joining proteins in both lymphogenesis and
neurogenesis. Cell 95, 891-902
8. Rehen, S. K., Yung, Y. C., McCreight, M. P., Kaushal, D., Yang, A. H., Almeida, B. S.,
Kingsbury, M. A., Cabral, K. M., McConnell, M. J., Anliker, B., Fontanoz, M., and
Chun, J. (2005) Constitutional aneuploidy in the normal human brain. J Neurosci 25,
2176-2180
9. Rehen, S. K., McConnell, M. J., Kaushal, D., Kingsbury, M. A., Yang, A. H., and Chun,
J. (2001) Chromosomal variation in neurons of the developing and adult mammalian
nervous system. Proc Natl Acad Sci U S A 98, 13361-13366
10. Westra, J. W., Peterson, S. E., Yung, Y. C., Mutoh, T., Barral, S., and Chun, J. (2008)
Aneuploid mosaicism in the developing and adult cerebellar cortex. J Comp Neurol 507,
1944-1951
11. Yurov, Y. B., Iourov, I. Y., Monakhov, V. V., Soloviev, I. V., Vostrikov, V. M., and
Vorsanova, S. G. (2005) The variation of aneuploidy frequency in the developing and
adult human brain revealed by an interphase FISH study. J Histochem Cytochem 53, 385-
390
12. Cai, X., Evrony, G. D., Lehmann, H. S., Elhosary, P. C., Mehta, B. K., Poduri, A., and
Walsh, C. A. (2014) Single-cell, genome-wide sequencing identifies clonal somatic copy-
number variation in the human brain. Cell Rep 8, 1280-1289
13. McConnell, M. J., Lindberg, M. R., Brennand, K. J., Piper, J. C., Voet, T., Cowing-
Zitron, C., Shumilina, S., Lasken, R. S., Vermeesch, J. R., Hall, I. M., and Gage, F. H.
(2013) Mosaic copy number variation in human neurons. Science 342, 632-637
14. Gole, J., Gore, A., Richards, A., Chiu, Y. J., Fung, H. L., Bushman, D., Chiang, H. I.,
Chun, J., Lo, Y. H., and Zhang, K. (2013) Massively parallel polymerase cloning and
genome sequencing of single cells using nanoliter microwells. Nat Biotechnol 31, 1126-
1132

10
 Somatic gene recombination in post-mitotic neurons

15. Rohrback, S., April, C., Kaper, F., Rivera, R. R., Liu, C. S., Siddoway, B., and Chun, J.
(2018) Submegabase copy number variations arise during cerebral cortical neurogenesis
as revealed by single-cell whole-genome sequencing. Proc Natl Acad Sci U S A 115,
10804-10809
16. Evrony, G. D., Lee, E., Park, P. J., and Walsh, C. A. (2016) Resolving rates of mutation
in the brain using single-neuron genomics. Elife 5
17. Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M.,
Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden,
T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., and Walsh, C. A. (2018)
Aging and neurodegeneration are associated with increased mutations in single human
neurons. Science 359, 555-559
18. Coufal, N. G., Garcia-Perez, J. L., Peng, G. E., Yeo, G. W., Mu, Y., Lovci, M. T., Morell,
M., O'Shea, K. S., Moran, J. V., and Gage, F. H. (2009) L1 retrotransposition in human
neural progenitor cells. Nature 460, 1127-1131
19. Muotri, A. R., Chu, V. T., Marchetto, M. C., Deng, W., Moran, J. V., and Gage, F. H.
(2005) Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition.

Downloaded from http://www.jbc.org/ by guest on July 23, 2020

Nature 435, 903-910
20. Baillie, J. K., Barnett, M. W., Upton, K. R., Gerhardt, D. J., Richmond, T. A., De Sapio,
F., Brennan, P. M., Rizzu, P., Smith, S., Fell, M., Talbot, R. T., Gustincich, S., Freeman,
T. C., Mattick, J. S., Hume, D. A., Heutink, P., Carninci, P., Jeddeloh, J. A., and
Faulkner, G. J. (2011) Somatic retrotransposition alters the genetic landscape of the
human brain. Nature 479, 534-537
21. Upton, K. R., Gerhardt, D. J., Jesuadian, J. S., Richardson, S. R., Sanchez-Luque, F. J.,
Bodea, G. O., Ewing, A. D., Salvador-Palomeque, C., van der Knaap, M. S., Brennan, P.
M., Vanderver, A., and Faulkner, G. J. (2015) Ubiquitous L1 mosaicism in hippocampal
neurons. Cell 161, 228-239
22. Bushman, D. M., Kaeser, G. E., Siddoway, B., Westra, J. W., Rivera, R. R., Rehen, S. K.,
Yung, Y. C., and Chun, J. (2015) Genomic mosaicism with increased amyloid precursor
protein (APP) gene copy number in single neurons from sporadic Alzheimer's disease
brains. Elife 4
23. Westra, J. W., Rivera, R. R., Bushman, D. M., Yung, Y. C., Peterson, S. E., Barral, S.,
and Chun, J. (2010) Neuronal DNA content variation (DCV) with regional and individual
differences in the human brain. J Comp Neurol 518, 3981-4000
24. Fischer, H. G., Morawski, M., Bruckner, M. K., Mittag, A., Tarnok, A., and Arendt, T.
(2012) Changes in neuronal DNA content variation in the human brain during aging.
Aging Cell 11, 628-633
25. Bushman, D. M., and Chun, J. (2013) The genomically mosaic brain: aneuploidy and
more in neural diversity and disease. Semin Cell Dev Biol 24, 357-369
26. Rohrback, S., Siddoway, B., Liu, C. S., and Chun, J. (2018) Genomic mosaicism in the
developing and adult brain. Dev Neurobiol 78, 1026-1048
27. Kingsbury, M. A., Friedman, B., McConnell, M. J., Rehen, S. K., Yang, A. H., Kaushal,
D., and Chun, J. (2005) Aneuploid neurons are functionally active and integrated into
brain circuitry. Proc Natl Acad Sci U S A 102, 6143-6147
28. Kaushal, D., Contos, J. J., Treuner, K., Yang, A. H., Kingsbury, M. A., Rehen, S. K.,
McConnell, M. J., Okabe, M., Barlow, C., and Chun, J. (2003) Alteration of gene
expression by chromosome loss in the postnatal mouse brain. J Neurosci 23, 5599-5606

11
 Somatic gene recombination in post-mitotic neurons

29. Peterson, S. E., Yang, A. H., Bushman, D. M., Westra, J. W., Yung, Y. C., Barral, S.,
Mutoh, T., Rehen, S. K., and Chun, J. (2012) Aneuploid cells are differentially
susceptible to caspase-mediated death during embryonic cerebral cortical development. J
Neurosci 32, 16213-16222
30. Hecker, A., Schulze, W., Oster, J., Richter, D. O., and Schuster, S. (2020) Removing a
single neuron in a vertebrate brain forever abolishes an essential behavior. Proc Natl
Acad Sci U S A 117, 3254-3260
31. Okuyama, T. (2018) Social memory engram in the hippocampus. Neuroscience research
129, 17-23
32. Gross, C. G. (2002) Genealogy of the "grandmother cell". Neuroscientist 8, 512-518
33. Nicolas, G., and Veltman, J. A. (2019) The role of de novo mutations in adult-onset
neurodegenerative disorders. Acta Neuropathol 137, 183-207
34. Lee, M. H., Siddoway, B., Kaeser, G. E., Segota, I., Rivera, R., Romanow, W. J., Liu, C.
S., Park, C., Kennedy, G., Long, T., and Chun, J. (2018) Somatic APP gene
recombination in Alzheimer's disease and normal neurons. Nature 563, 639-645
35. Roth, D. B. (2014) V(D)J Recombination: Mechanism, Errors, and Fidelity. Microbiol

Downloaded from http://www.jbc.org/ by guest on July 23, 2020

Spectr 2
36. Schatz, D. G., and Swanson, P. C. (2011) V(D)J recombination: mechanisms of initiation.
Annu Rev Genet 45, 167-202
37. Park, J. S., Lee, J., Jung, E. S., Kim, M. H., Kim, I. B., Son, H., Kim, S., Kim, S., Park,
Y. M., Mook-Jung, I., Yu, S. J., and Lee, J. H. (2019) Brain somatic mutations observed
in Alzheimer's disease associated with aging and dysregulation of tau phosphorylation.
Nat Commun 10, 3090
38. Lee, M.-H., Liu, C. S., Zhu, Y., Kaeser, G. E., Rivera, R., Romanow, W. J., Kihara, Y.,
and Chun, J. (2020) Reply: Evidence that APP gene copy number changes reflect
recombinant vector contamination Nature
39. (2016) Data Release: Alzheimer Brain Isoform Sequencing (Iso-Seq) Dataset.
40. Carmona, L. M., and Schatz, D. G. (2017) New insights into the evolutionary origins of
the recombination-activating gene proteins and V(D)J recombination. FEBS J 284, 1590-
1605
41. Schatz, D. G., and Ji, Y. (2011) Recombination centres and the orchestration of V(D)J
recombination. Nat Rev Immunol 11, 251-263
42. Schatz, D. G., and Baltimore, D. (2004) Uncovering the V(D)J recombinase. Cell 116,
S103-106, 102 p following S106
43. Merelli, I., Guffanti, A., Fabbri, M., Cocito, A., Furia, L., Grazini, U., Bonnal, R. J.,
Milanesi, L., and McBlane, F. (2010) RSSsite: a reference database and prediction tool
for the identification of cryptic Recombination Signal Sequences in human and murine
genomes. Nucleic Acids Res 38, W262-267
44. Lee, A. I., Fugmann, S. D., Cowell, L. G., Ptaszek, L. M., Kelsoe, G., and Schatz, D. G.
(2003) A functional analysis of the spacer of V(D)J recombination signal sequences.
PLoS Biol 1, E1
45. Rahman, N. S., Godderz, L. J., Stray, S. J., Capra, J. D., and Rodgers, K. K. (2006) DNA
cleavage of a cryptic recombination signal sequence by RAG1 and RAG2. Implications
for partial V(H) gene replacement. J Biol Chem 281, 12370-12380

12
 Somatic gene recombination in post-mitotic neurons

46. Numata, M., Saito, S., and Nagata, K. (2010) RAG-dependent recombination at cryptic
RSSs within TEL-AML1 t(12;21)(p13;q22) chromosomal translocation region. Biochem
Biophys Res Commun 402, 718-724
47. Lieber, M. R., Yu, K., and Raghavan, S. C. (2006) Roles of nonhomologous DNA end
joining, V(D)J recombination, and class switch recombination in chromosomal
translocations. DNA Repair (Amst) 5, 1234-1245
48. Dudley, D. D., Chaudhuri, J., Bassing, C. H., and Alt, F. W. (2005) Mechanism and
control of V(D)J recombination versus class switch recombination: similarities and
differences. Adv Immunol 86, 43-112
49. Methot, S. P., and Di Noia, J. M. (2017) Molecular Mechanisms of Somatic
Hypermutation and Class Switch Recombination. Adv Immunol 133, 37-87
50. Xu, Z., Zan, H., Pone, E. J., Mai, T., and Casali, P. (2012) Immunoglobulin class-switch
DNA recombination: induction, targeting and beyond. Nat Rev Immunol 12, 517-531
51. Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon,
K., Dewar, K., Doyle, M., FitzHugh, W., Funke, R., Gage, D., Harris, K., Heaford, A.,
Howland, J., Kann, L., Lehoczky, J., LeVine, R., McEwan, P., McKernan, K., Meldrim,

Downloaded from http://www.jbc.org/ by guest on July 23, 2020

J., Mesirov, J. P., Miranda, C., Morris, W., Naylor, J., Raymond, C., Rosetti, M., Santos,
R., Sheridan, A., Sougnez, C., Stange-Thomann, Y., Stojanovic, N., Subramanian, A.,
Wyman, D., Rogers, J., Sulston, J., Ainscough, R., Beck, S., Bentley, D., Burton, J., Clee,
C., Carter, N., Coulson, A., Deadman, R., Deloukas, P., Dunham, A., Dunham, I.,
Durbin, R., French, L., Grafham, D., Gregory, S., Hubbard, T., Humphray, S., Hunt, A.,
Jones, M., Lloyd, C., McMurray, A., Matthews, L., Mercer, S., Milne, S., Mullikin, J. C.,
Mungall, A., Plumb, R., Ross, M., Shownkeen, R., Sims, S., Waterston, R. H., Wilson, R.
K., Hillier, L. W., McPherson, J. D., Marra, M. A., Mardis, E. R., Fulton, L. A.,
Chinwalla, A. T., Pepin, K. H., Gish, W. R., Chissoe, S. L., Wendl, M. C., Delehaunty,
K. D., Miner, T. L., Delehaunty, A., Kramer, J. B., Cook, L. L., Fulton, R. S., Johnson,
D. L., Minx, P. J., Clifton, S. W., Hawkins, T., Branscomb, E., Predki, P., Richardson, P.,
Wenning, S., Slezak, T., Doggett, N., Cheng, J. F., Olsen, A., Lucas, S., Elkin, C.,
Uberbacher, E., Frazier, M., Gibbs, R. A., Muzny, D. M., Scherer, S. E., Bouck, J. B.,
Sodergren, E. J., Worley, K. C., Rives, C. M., Gorrell, J. H., Metzker, M. L., Naylor, S.
L., Kucherlapati, R. S., Nelson, D. L., Weinstock, G. M., Sakaki, Y., Fujiyama, A.,
Hattori, M., Yada, T., Toyoda, A., Itoh, T., Kawagoe, C., Watanabe, H., Totoki, Y.,
Taylor, T., Weissenbach, J., Heilig, R., Saurin, W., Artiguenave, F., Brottier, P., Bruls,
T., Pelletier, E., Robert, C., Wincker, P., Smith, D. R., Doucette-Stamm, L., Rubenfield,
M., Weinstock, K., Lee, H. M., Dubois, J., Rosenthal, A., Platzer, M., Nyakatura, G.,
Taudien, S., Rump, A., Yang, H., Yu, J., Wang, J., Huang, G., Gu, J., Hood, L., Rowen,
L., Madan, A., Qin, S., Davis, R. W., Federspiel, N. A., Abola, A. P., Proctor, M. J.,
Myers, R. M., Schmutz, J., Dickson, M., Grimwood, J., Cox, D. R., Olson, M. V., Kaul,
R., Raymond, C., Shimizu, N., Kawasaki, K., Minoshima, S., Evans, G. A., Athanasiou,
M., Schultz, R., Roe, B. A., Chen, F., Pan, H., Ramser, J., Lehrach, H., Reinhardt, R.,
McCombie, W. R., de la Bastide, M., Dedhia, N., Blocker, H., Hornischer, K., Nordsiek,
G., Agarwala, R., Aravind, L., Bailey, J. A., Bateman, A., Batzoglou, S., Birney, E.,
Bork, P., Brown, D. G., Burge, C. B., Cerutti, L., Chen, H. C., Church, D., Clamp, M.,
Copley, R. R., Doerks, T., Eddy, S. R., Eichler, E. E., Furey, T. S., Galagan, J., Gilbert, J.
G., Harmon, C., Hayashizaki, Y., Haussler, D., Hermjakob, H., Hokamp, K., Jang, W.,
Johnson, L. S., Jones, T. A., Kasif, S., Kaspryzk, A., Kennedy, S., Kent, W. J., Kitts, P.,

13
 Somatic gene recombination in post-mitotic neurons

Koonin, E. V., Korf, I., Kulp, D., Lancet, D., Lowe, T. M., McLysaght, A., Mikkelsen,
T., Moran, J. V., Mulder, N., Pollara, V. J., Ponting, C. P., Schuler, G., Schultz, J., Slater,
G., Smit, A. F., Stupka, E., Szustakowki, J., Thierry-Mieg, D., Thierry-Mieg, J., Wagner,
L., Wallis, J., Wheeler, R., Williams, A., Wolf, Y. I., Wolfe, K. H., Yang, S. P., Yeh, R.
F., Collins, F., Guyer, M. S., Peterson, J., Felsenfeld, A., Wetterstrand, K. A., Patrinos,
A., Morgan, M. J., de Jong, P., Catanese, J. J., Osoegawa, K., Shizuya, H., Choi, S.,
Chen, Y. J., Szustakowki, J., and International Human Genome Sequencing, C. (2001)
Initial sequencing and analysis of the human genome. Nature 409, 860-921
52. Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith,
H. O., Yandell, M., Evans, C. A., Holt, R. A., Gocayne, J. D., Amanatides, P., Ballew, R.
M., Huson, D. H., Wortman, J. R., Zhang, Q., Kodira, C. D., Zheng, X. H., Chen, L.,
Skupski, M., Subramanian, G., Thomas, P. D., Zhang, J., Gabor Miklos, G. L., Nelson,
C., Broder, S., Clark, A. G., Nadeau, J., McKusick, V. A., Zinder, N., Levine, A. J.,
Roberts, R. J., Simon, M., Slayman, C., Hunkapiller, M., Bolanos, R., Delcher, A., Dew,
I., Fasulo, D., Flanigan, M., Florea, L., Halpern, A., Hannenhalli, S., Kravitz, S., Levy,
S., Mobarry, C., Reinert, K., Remington, K., Abu-Threideh, J., Beasley, E., Biddick, K.,

Downloaded from http://www.jbc.org/ by guest on July 23, 2020

Bonazzi, V., Brandon, R., Cargill, M., Chandramouliswaran, I., Charlab, R., Chaturvedi,
K., Deng, Z., Di Francesco, V., Dunn, P., Eilbeck, K., Evangelista, C., Gabrielian, A. E.,
Gan, W., Ge, W., Gong, F., Gu, Z., Guan, P., Heiman, T. J., Higgins, M. E., Ji, R. R., Ke,
Z., Ketchum, K. A., Lai, Z., Lei, Y., Li, Z., Li, J., Liang, Y., Lin, X., Lu, F., Merkulov, G.
V., Milshina, N., Moore, H. M., Naik, A. K., Narayan, V. A., Neelam, B., Nusskern, D.,
Rusch, D. B., Salzberg, S., Shao, W., Shue, B., Sun, J., Wang, Z., Wang, A., Wang, X.,
Wang, J., Wei, M., Wides, R., Xiao, C., Yan, C., Yao, A., Ye, J., Zhan, M., Zhang, W.,
Zhang, H., Zhao, Q., Zheng, L., Zhong, F., Zhong, W., Zhu, S., Zhao, S., Gilbert, D.,
Baumhueter, S., Spier, G., Carter, C., Cravchik, A., Woodage, T., Ali, F., An, H., Awe,
A., Baldwin, D., Baden, H., Barnstead, M., Barrow, I., Beeson, K., Busam, D., Carver,
A., Center, A., Cheng, M. L., Curry, L., Danaher, S., Davenport, L., Desilets, R., Dietz,
S., Dodson, K., Doup, L., Ferriera, S., Garg, N., Gluecksmann, A., Hart, B., Haynes, J.,
Haynes, C., Heiner, C., Hladun, S., Hostin, D., Houck, J., Howland, T., Ibegwam, C.,
Johnson, J., Kalush, F., Kline, L., Koduru, S., Love, A., Mann, F., May, D., McCawley,
S., McIntosh, T., McMullen, I., Moy, M., Moy, L., Murphy, B., Nelson, K., Pfannkoch,
C., Pratts, E., Puri, V., Qureshi, H., Reardon, M., Rodriguez, R., Rogers, Y. H., Romblad,
D., Ruhfel, B., Scott, R., Sitter, C., Smallwood, M., Stewart, E., Strong, R., Suh, E.,
Thomas, R., Tint, N. N., Tse, S., Vech, C., Wang, G., Wetter, J., Williams, S., Williams,
M., Windsor, S., Winn-Deen, E., Wolfe, K., Zaveri, J., Zaveri, K., Abril, J. F., Guigo, R.,
Campbell, M. J., Sjolander, K. V., Karlak, B., Kejariwal, A., Mi, H., Lazareva, B.,
Hatton, T., Narechania, A., Diemer, K., Muruganujan, A., Guo, N., Sato, S., Bafna, V.,
Istrail, S., Lippert, R., Schwartz, R., Walenz, B., Yooseph, S., Allen, D., Basu, A.,
Baxendale, J., Blick, L., Caminha, M., Carnes-Stine, J., Caulk, P., Chiang, Y. H., Coyne,
M., Dahlke, C., Mays, A., Dombroski, M., Donnelly, M., Ely, D., Esparham, S., Fosler,
C., Gire, H., Glanowski, S., Glasser, K., Glodek, A., Gorokhov, M., Graham, K.,
Gropman, B., Harris, M., Heil, J., Henderson, S., Hoover, J., Jennings, D., Jordan, C.,
Jordan, J., Kasha, J., Kagan, L., Kraft, C., Levitsky, A., Lewis, M., Liu, X., Lopez, J.,
Ma, D., Majoros, W., McDaniel, J., Murphy, S., Newman, M., Nguyen, T., Nguyen, N.,
Nodell, M., Pan, S., Peck, J., Peterson, M., Rowe, W., Sanders, R., Scott, J., Simpson,
M., Smith, T., Sprague, A., Stockwell, T., Turner, R., Venter, E., Wang, M., Wen, M.,

14
 Somatic gene recombination in post-mitotic neurons

Wu, D., Wu, M., Xia, A., Zandieh, A., and Zhu, X. (2001) The sequence of the human
genome. Science 291, 1304-1351
53. Chorev, M., and Carmel, L. (2012) The function of introns. Front Genet 3, 55
54. Goffeau, A., Barrell, B. G., Bussey, H., Davis, R. W., Dujon, B., Feldmann, H., Galibert,
F., Hoheisel, J. D., Jacq, C., Johnston, M., Louis, E. J., Mewes, H. W., Murakami, Y.,
Philippsen, P., Tettelin, H., and Oliver, S. G. (1996) Life with 6000 genes. Science 274,
546, 563-547
55. Kellis, M., Patterson, N., Endrizzi, M., Birren, B., and Lander, E. S. (2003) Sequencing
and comparison of yeast species to identify genes and regulatory elements. Nature 423,
241-254
56. Spingola, M., Grate, L., Haussler, D., and Ares, M., Jr. (1999) Genome-wide
bioinformatic and molecular analysis of introns in Saccharomyces cerevisiae. RNA 5,
221-234
57. Csuros, M., Rogozin, I. B., and Koonin, E. V. (2011) A detailed history of intron-rich
eukaryotic ancestors inferred from a global survey of 100 complete genomes. PLoS
Comput Biol 7, e1002150

Downloaded from http://www.jbc.org/ by guest on July 23, 2020

58. Juneau, K., Miranda, M., Hillenmeyer, M. E., Nislow, C., and Davis, R. W. (2006)
Introns regulate RNA and protein abundance in yeast. Genetics 174, 511-518
59. Parenteau, J., Durand, M., Veronneau, S., Lacombe, A. A., Morin, G., Guerin, V., Cecez,
B., Gervais-Bird, J., Koh, C. S., Brunelle, D., Wellinger, R. J., Chabot, B., and Abou
Elela, S. (2008) Deletion of many yeast introns reveals a minority of genes that require
splicing for function. Mol Biol Cell 19, 1932-1941
60. Cuenca, A., Ross, T. G., Graham, S. W., Barrett, C. F., Davis, J. I., Seberg, O., and
Petersen, G. (2016) Localized Retroprocessing as a Model of Intron Loss in the Plant
Mitochondrial Genome. Genome Biol Evol 8, 2176-2189
61. Pogoda, C. S., Keepers, K. G., Nadiadi, A. Y., Bailey, D. W., Lendemer, J. C., Tripp, E.
A., and Kane, N. C. (2019) Genome streamlining via complete loss of introns has
occurred multiple times in lichenized fungal mitochondria. Ecol Evol 9, 4245-4263
62. Coulombe-Huntington, J., and Majewski, J. (2007) Characterization of intron loss events
in mammals. Genome Res 17, 23-32
63. Lane, N., and Martin, W. (2010) The energetics of genome complexity. Nature 467, 929-
934
64. Irimia, M., Penny, D., and Roy, S. W. (2007) Coevolution of genomic intron number and
splice sites. Trends Genet 23, 321-325
65. Zhu, T., and Niu, D. K. (2013) Frequency of intron loss correlates with processed
pseudogene abundance: a novel strategy to test the reverse transcriptase model of intron
loss. BMC Biol 11, 23
66. Fink, G. R. (1987) Pseudogenes in yeast? Cell 49, 5-6
67. Derr, L. K., Strathern, J. N., and Garfinkel, D. J. (1991) RNA-mediated recombination in
S. cerevisiae. Cell 67, 355-364
68. Roy, S. W., and Gilbert, W. (2005) The pattern of intron loss. Proc Natl Acad Sci U S A
102, 713-718
69. Roy, S. W., and Gilbert, W. (2006) The evolution of spliceosomal introns: patterns,
puzzles and progress. Nat Rev Genet 7, 211-221

15
 Somatic gene recombination in post-mitotic neurons

70. Curcio, M. J., Lutz, S., and Lesage, P. (2014) The Ty1 LTR-Retrotransposon of Budding
Yeast, Saccharomyces cerevisiae. in Mobile DNA, 3rd Ed., 2014 American Society for
Microbiology, Washington, DC. pp 927-964
71. Derr, L. K. (1998) The involvement of cellular recombination and repair genes in RNA-
mediated recombination in Saccharomyces cerevisiae. Genetics 148, 937-945
72. Derr, L. K., and Strathern, J. N. (1993) A role for reverse transcripts in gene conversion.
Nature 361, 170-173
73. Catania, F. (2017) From intronization to intron loss: How the interplay between mRNA-
associated processes can shape the architecture and the expression of eukaryotic genes.
Int J Biochem Cell Biol 91, 136-144
74. Maxwell, P. H., and Curcio, M. J. (2007) Retrosequence formation restructures the yeast
genome. Genes Dev 21, 3308-3318
75. Welty, S., Teng, Y., Liang, Z., Zhao, W., Sanders, L. H., Greenamyre, J. T., Rubio, M.
E., Thathiah, A., Kodali, R., Wetzel, R., Levine, A. S., and Lan, L. (2018) RAD52 is
required for RNA-templated recombination repair in post-mitotic neurons. J Biol Chem
293, 1353-1362

Downloaded from http://www.jbc.org/ by guest on July 23, 2020

76. Kovalenko, T. F., and Patrushev, L. I. (2018) Pseudogenes as Functionally Significant
Elements of the Genome. Biochemistry (Mosc) 83, 1332-1349
77. Balakirev, E. S., and Ayala, F. J. (2003) Pseudogenes: are they "junk" or functional
DNA? Annu Rev Genet 37, 123-151
78. Kazazian, H. H., Jr. (2014) Processed pseudogene insertions in somatic cells. Mob DNA
5, 20
79. Cooke, S. L., Shlien, A., Marshall, J., Pipinikas, C. P., Martincorena, I., Tubio, J. M., Li,
Y., Menzies, A., Mudie, L., Ramakrishna, M., Yates, L., Davies, H., Bolli, N., Bignell, G.
R., Tarpey, P. S., Behjati, S., Nik-Zainal, S., Papaemmanuil, E., Teixeira, V. H., Raine,
K., O'Meara, S., Dodoran, M. S., Teague, J. W., Butler, A. P., Iacobuzio-Donahue, C.,
Santarius, T., Grundy, R. G., Malkin, D., Greaves, M., Munshi, N., Flanagan, A. M.,
Bowtell, D., Martin, S., Larsimont, D., Reis-Filho, J. S., Boussioutas, A., Taylor, J. A.,
Hayes, N. D., Janes, S. M., Futreal, P. A., Stratton, M. R., McDermott, U., Campbell, P.
J., and Group, I. B. C. (2014) Processed pseudogenes acquired somatically during cancer
development. Nat Commun 5, 3644
80. Seol, J. H., Shim, E. Y., and Lee, S. E. (2018) Microhomology-mediated end joining:
Good, bad and ugly. Mutat Res 809, 81-87
81. Sfeir, A., and Symington, L. S. (2015) Microhomology-Mediated End Joining: A Back-
up Survival Mechanism or Dedicated Pathway? Trends Biochem Sci 40, 701-714
82. Richardson, S. R., Morell, S., and Faulkner, G. J. (2014) L1 retrotransposons and somatic
mosaicism in the brain. Annu Rev Genet 48, 1-27
83. Nelson, P. N., Hooley, P., Roden, D., Davari Ejtehadi, H., Rylance, P., Warren, P.,
Martin, J., Murray, P. G., and Molecular Immunology Research, G. (2004) Human
endogenous retroviruses: transposable elements with potential? Clin Exp Immunol 138, 1-
9
84. Esnault, C., Maestre, J., and Heidmann, T. (2000) Human LINE retrotransposons
generate processed pseudogenes. Nat Genet 24, 363-367
85. Faulkner, G. J., and Garcia-Perez, J. L. (2017) L1 Mosaicism in Mammals: Extent,
Effects, and Evolution. Trends Genet 33, 802-816

16
 Somatic gene recombination in post-mitotic neurons

86. Ding, W., Lin, L., Chen, B., and Dai, J. (2006) L1 elements, processed pseudogenes and
retrogenes in mammalian genomes. IUBMB Life 58, 677-685
87. Evrony, G. D., Cai, X., Lee, E., Hills, L. B., Elhosary, P. C., Lehmann, H. S., Parker, J.
J., Atabay, K. D., Gilmore, E. C., Poduri, A., Park, P. J., and Walsh, C. A. (2012) Single-
neuron sequencing analysis of L1 retrotransposition and somatic mutation in the human
brain. Cell 151, 483-496
88. Terry, D. M., and Devine, S. E. (2019) Aberrantly High Levels of Somatic LINE-1
Expression and Retrotransposition in Human Neurological Disorders. Front Genet 10,
1244
89. Kapitonov, V. V., and Jurka, J. (2005) RAG1 core and V(D)J recombination signal
sequences were derived from Transib transposons. PLoS Biol 3, e181
90. Kapitonov, V. V., and Koonin, E. V. (2015) Evolution of the RAG1-RAG2 locus: both
proteins came from the same transposon. Biol Direct 10, 20
91. Zhang, Y., Cheng, T. C., Huang, G., Lu, Q., Surleac, M. D., Mandell, J. D., Pontarotti, P.,
Petrescu, A. J., Xu, A., Xiong, Y., and Schatz, D. G. (2019) Transposon molecular
domestication and the evolution of the RAG recombinase. Nature 569, 79-84

Downloaded from http://www.jbc.org/ by guest on July 23, 2020

92. Liu, C., Yang, Y., and Schatz, D. G. (2019) Structures of a RAG-like transposase during
cut-and-paste transposition. Nature 575, 540-544
93. Huang, S., Tao, X., Yuan, S., Zhang, Y., Li, P., Beilinson, H. A., Zhang, Y., Yu, W.,
Pontarotti, P., Escriva, H., Le Petillon, Y., Liu, X., Chen, S., Schatz, D. G., and Xu, A.
(2016) Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J
Recombination. Cell 166, 102-114
94. Agrawal, A., Eastman, Q. M., and Schatz, D. G. (1998) Transposition mediated by RAG1
and RAG2 and its implications for the evolution of the immune system. Nature 394, 744-
751
95. Hiom, K., Melek, M., and Gellert, M. (1998) DNA transposition by the RAG1 and RAG2
proteins: a possible source of oncogenic translocations. Cell 94, 463-470
96. Brandt, V. L., and Roth, D. B. (2004) V(D)J recombination: how to tame a transposase.
Immunol Rev 200, 249-260
97. Lake, B. B., Ai, R., Kaeser, G. E., Salathia, N. S., Yung, Y. C., Liu, R., Wildberg, A.,
Gao, D., Fung, H. L., Chen, S., Vijayaraghavan, R., Wong, J., Chen, A., Sheng, X.,
Kaper, F., Shen, R., Ronaghi, M., Fan, J. B., Wang, W., Chun, J., and Zhang, K. (2016)
Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the
human brain. Science 352, 1586-1590
98. Treiber, C. D., and Waddell, S. (2019) Transposon expression in the Drosophila brain is
driven by neighboring genes and diversifies the neural transcriptome. bioRxiv
99. Leija-Salazar, M., Piette, C., and Proukakis, C. (2018) Review: Somatic mutations in
neurodegeneration. Neuropathol Appl Neurobiol 44, 267-285
100. Maxwell, P. H. (2016) What might retrotransposons teach us about aging? Curr Genet
62, 277-282
101. Li, W., Prazak, L., Chatterjee, N., Gruninger, S., Krug, L., Theodorou, D., and Dubnau, J.
(2013) Activation of transposable elements during aging and neuronal decline in
Drosophila. Nat Neurosci 16, 529-531
102. Muotri, A. R., Zhao, C., Marchetto, M. C., and Gage, F. H. (2009) Environmental
influence on L1 retrotransposons in the adult hippocampus. Hippocampus 19, 1002-1007

17