Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk

Abstract
Data availability
Article and author information
Metrics

Abstract

The risk of developing cancer is correlated with body size and lifespan within species. Between species, however, there is no correlation between cancer and either body size or lifespan, indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Elephants and their relatives (Proboscideans) are a particularly interesting lineage for the exploration of mechanisms underlying the evolution of augmented cancer resistance because they evolved large bodies recently within a clade of smaller bodied species (Afrotherians). Here, we explore the contribution of gene duplication to body size and cancer risk in Afrotherians. Unexpectedly, we found that tumor suppressor duplication was pervasive in Afrotherian genomes, rather than restricted to Proboscideans. Proboscideans, however, have duplicates in unique pathways that may underlie some aspects of their remarkable anti-cancer cell biology. These data suggest that duplication of tumor suppressor genes facilitated the evolution of increased body size by compensating for decreasing intrinsic cancer risk.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

1. Di Palma
2. F.
3. Alfoldi
4. J.
5. Johnson
6. J.
7. Berlin
8. A.
9. Gnerre
10. S.
11. Jaffe
12. D.
13. MacCallum
14. I.
15. Young
16. S.
17. Walker
18. B.J. and Lindblad-Toh
19. K.
(2013) Chrysochloris asiatica (Cape golden mole) genome
ChrAsi1.0.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000296735.1/
1. Gnerre
2. S.
3. Heiman
4. D.
5. Young
6. S.
7. Fulton
8. L.
9. Delehaunty
10. K.
11. Minx
12. P.
13. Chinwalla
14. A.
15. Mardis
16. E.
17. Wilson
18. R. and Warren
19. W
(2018) The Genome Sequence of Choloepus hoffmanni (sloth)
C_hoffmanni-2.0.1_HiC.

https://www.dnazoo.org/assemblies/Choloepus_hoffmanni
1. Lindblad-Toh
2. K.
3. Chang
4. J.L.
5. Gnerre
6. S.
7. Clamp
8. M. and Lander
9. E.S.
(2012) Dasypus novemcinctus (nine-banded armadillo) genome
Dasnov3.0.

https://www.ncbi.nlm.nih.gov/assembly/GCA_000208655.2/
1. Di Palma
2. F.
3. Alfoldi
4. J.
5. Johnson
6. J.
7. Berlin
8. A.
9. Gnerre
10. S.
11. Jaffe
12. D.
13. MacCallum
14. I.
15. Young
16. S.
17. Walker
18. B.J. and Lindblad-Toh
19. K.
(2013) Echinops telfairi (small Madagascar hedgehog)
EchTel2.0.

https://www.ncbi.nlm.nih.gov/assembly/GCA_000313985.1/
1. Di Palma
2. F.
3. Alfoldi
4. J.
5. Johnson
6. J.
7. Berlin
8. A.
9. Gnerre
10. S.
11. Jaffe
12. D.
13. MacCallum
14. I.
15. Young
16. S.
17. Walker
18. B.J. and Lindblad-Toh
19. K.
(2013) Elephantulus edwardii (Cape elephant shrew)
EleEdw1.0.

https://www.ncbi.nlm.nih.gov/assembly/GCA_000299155.1/
1. Palkopoulou E
2. Lipson M
3. Mallick S
4. Nielsen S
5. Rohland N
6. Baleka S
7. Karpinski E
8. Ivancevic AM
9. To TH
10. Kortschak RD
11. Raison JM
12. Qu Z
13. Chin TJ
14. Alt KW
15. Claesson S
16. Dalén L
17. MacPhee RDE
18. Meller H
19. Roca AL
20. Ryder OA
21. Heiman D
22. Young S
23. Breen M
24. Williams C
25. Aken BL
26. Ruffier M
27. Karlsson E
28. Johnson J
29. Di Palma F
30. Alfoldi J
31. Adelson DL
32. Mailund T
33. Munch K
34. Lindblad-Toh K
35. Hofreiter M
36. Poinar H
37. Reich D
(2018) A comprehensive genomic history of extinct and living elephants
eleMaxD.

https://www.ebi.ac.uk/ena/browser/view/PRJEB24361
1. Palkopoulou E
2. Lipson M
3. Mallick S
4. Nielsen S
5. Rohland N
6. Baleka S
7. Karpinski E
8. Ivancevic AM
9. To TH
10. Kortschak RD
11. Raison JM
12. Qu Z
13. Chin TJ
14. Alt KW
15. Claesson S
16. Dalén L
17. MacPhee RDE
18. Meller H
19. Roca AL
20. Ryder OA
21. Heiman D
22. Young S
23. Breen M
24. Williams C
25. Aken BL
26. Ruffier M
27. Karlsson E
28. Johnson J
29. Di Palma F
30. Alfoldi J
31. Adelson DL
32. Mailund T
33. Munch K
34. Lindblad-Toh K
35. Hofreiter M
36. Poinar H
37. Reich D
(2018) A comprehensive genomic history of extinct and living elephants
LoxAfr4.

https://www.ebi.ac.uk/ena/browser/view/PRJEB24361
1. Palkopoulou E
2. Lipson M
3. Mallick S
4. Nielsen S
5. Rohland N
6. Baleka S
7. Karpinski E
8. Ivancevic AM
9. To TH
10. Kortschak RD
11. Raison JM
12. Qu Z
13. Chin TJ
14. Alt KW
15. Claesson S
16. Dalén L
17. MacPhee RDE
18. Meller H
19. Roca AL
20. Ryder OA
21. Heiman D
22. Young S
23. Breen M
24. Williams C
25. Aken BL
26. Ruffier M
27. Karlsson E
28. Johnson J
29. Di Palma F
30. Alfoldi J
31. Adelson DL
32. Mailund T
33. Munch K
34. Lindblad-Toh K
35. Hofreiter M
36. Poinar H
37. Reich D
(2018) A comprehensive genomic history of extinct and living elephants
loxCycF.

https://www.ebi.ac.uk/ena/browser/view/PRJEB24361
1. Palkopoulou E
2. Lipson M
3. Mallick S
4. Nielsen S
5. Rohland N
6. Baleka S
7. Karpinski E
8. Ivancevic AM
9. To TH
10. Kortschak RD
11. Raison JM
12. Qu Z
13. Chin TJ
14. Alt KW
15. Claesson S
16. Dalén L
17. MacPhee RDE
18. Meller H
19. Roca AL
20. Ryder OA
21. Heiman D
22. Young S
23. Breen M
24. Williams C
25. Aken BL
26. Ruffier M
27. Karlsson E
28. Johnson J
29. Di Palma F
30. Alfoldi J
31. Adelson DL
32. Mailund T
33. Munch K
34. Lindblad-Toh K
35. Hofreiter M
36. Poinar H
37. Reich D
(2018) A comprehensive genomic history of extinct and living elephants
mamAmeI.

https://www.ebi.ac.uk/ena/browser/view/PRJEB24361
1. Palkopoulou E
2. Lipson M
3. Mallick S
4. Nielsen S
5. Rohland N
6. Baleka S
7. Karpinski E
8. Ivancevic AM
9. To TH
10. Kortschak RD
11. Raison JM
12. Qu Z
13. Chin TJ
14. Alt KW
15. Claesson S
16. Dalén L
17. MacPhee RDE
18. Meller H
19. Roca AL
20. Ryder OA
21. Heiman D
22. Young S
23. Breen M
24. Williams C
25. Aken BL
26. Ruffier M
27. Karlsson E
28. Johnson J
29. Di Palma F
30. Alfoldi J
31. Adelson DL
32. Mailund T
33. Munch K
34. Lindblad-Toh K
35. Hofreiter M
36. Poinar H
37. Reich D
(2018) A comprehensive genomic history of extinct and living elephants
mamColU.

https://www.ebi.ac.uk/ena/browser/view/PRJEB24361
1. Palkopoulou E
2. Lipson M
3. Mallick S
4. Nielsen S
5. Rohland N
6. Baleka S
7. Karpinski E
8. Ivancevic AM
9. To TH
10. Kortschak RD
11. Raison JM
12. Qu Z
13. Chin TJ
14. Alt KW
15. Claesson S
16. Dalén L
17. MacPhee RDE
18. Meller H
19. Roca AL
20. Ryder OA
21. Heiman D
22. Young S
23. Breen M
24. Williams C
25. Aken BL
26. Ruffier M
27. Karlsson E
28. Johnson J
29. Di Palma F
30. Alfoldi J
31. Adelson DL
32. Mailund T
33. Munch K
34. Lindblad-Toh K
35. Hofreiter M
36. Poinar H
37. Reich D
(2018) A comprehensive genomic history of extinct and living elephants
mamPriV.

https://www.ebi.ac.uk/ena/browser/view/PRJEB24361
1. Palkopoulou E
2. Lipson M
3. Mallick S
4. Nielsen S
5. Rohland N
6. Baleka S
7. Karpinski E
8. Ivancevic AM
9. To TH
10. Kortschak RD
11. Raison JM
12. Qu Z
13. Chin TJ
14. Alt KW
15. Claesson S
16. Dalén L
17. MacPhee RDE
18. Meller H
19. Roca AL
20. Ryder OA
21. Heiman D
22. Young S
23. Breen M
24. Williams C
25. Aken BL
26. Ruffier M
27. Karlsson E
28. Johnson J
29. Di Palma F
30. Alfoldi J
31. Adelson DL
32. Mailund T
33. Munch K
34. Lindblad-Toh K
35. Hofreiter M
36. Poinar H
37. Reich D
(2018) A comprehensive genomic history of extinct and living elephants
palAntN.

https://www.ebi.ac.uk/ena/browser/view/PRJEB24361
1. Di Palma
2. F.
3. Alfoldi
4. J.
5. Johnson
6. J.
7. Berlin
8. A.
9. Gnerre
10. S.
11. Jaffe
12. D.
13. MacCallum
14. I.
15. Young
16. S.
17. Walker
18. B.J. and Lindblad-Toh
19. K
(2017) Aardvark (Orycteropus afer) genome
oryAfe2.

https://www.dnazoo.org/assemblies/Orycteropus_afer
1. Di Palma
2. F.
3. Alfoldi
4. J.
5. Johnson
6. J.
7. Berlin
8. A.
9. Gnerre
10. S.
11. Jaffe
12. D.
13. MacCallum
14. I.
15. Young
16. S.
17. Walker
18. B.J. and Lindblad-Toh
19. K.
(2013) A comprehensive genomic history of extinct and living elephants
proCap-Pcap_2.0_HiC.

https://www.dnazoo.org/assemblies/Procavia_capensis
(2015) West Indian manatee (Trichechus manatus) genome
triManLat2.

https://www.dnazoo.org/assemblies/Trichechus_manatus

Article and author information

Author details

Juan M Vazquez

Department of Integrative Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Vincent J Lynch

Department of Biological Sciences, University at Buffalo, Buffalo, United States

For correspondence
vjlynch@buffalo.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5311-3824

Funding

University of Chicago

Juan M Vazquez
Vincent J Lynch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.