Biological Sciences Division
Published September 19, 2016 | Version v1
Journal article Open

TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants

Creators

  • 1. University of Chicago
  • 2. University of Nottingham

Description

A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as 'Peto's Paradox'. Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Furthermore, we show that several of the TP53 retrogenes (TP53RTGs) are transcribed and likely translated. While TP53RTGs do not appear to directly function as transcription factors, they do contribute to the enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis by regulating activity of the TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes and the resolution of Peto's paradox in Proboscideans.

Data availability

The following data sets were generated:

Sulak M Fong L Mika K Chigurupati S Yon L Mongan NP Emes RD Lynch VJ (2016) Data from: TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants Available at Dryad Digital Repository under a CC0 Public Domain Dedication. http://dx.doi.org/10.5061/dryad.968vr

The following previously published data sets were used:

Dastjerdi A Robert C Watson M (2014) Whole genome sequencing of two Asian elephants (Elephas maximus) infected with Elephant Endotheliotropic Herpesvirus (EEHV) Publicly available at the NCBI Short Read Archive (accession no: ERX334765, ERX334764). http://www.ncbi.nlm.nih.gov/bioproject/PRJEB4905

Enk J Rouillard J-M Poinar H (2013) Raw Illumina read files associated with Enk et al. publication on qPCR as a predictor of mapped reads after enrichment. Sequence data from non-enriched and enriched libraries deriving from Pleistocene-age bone and tooth remains of various Mammuthus sp. Publicly available at the NCBI Short Read Archive (accession no: SRX329134, SRX329135, SRX327587, SRX327586, SRX327583, SRX327582). http://www.ncbi.nlm.nih.gov/bioproject/PRJNA203139

Rohland N Reich D Mallick S Meyer M Green RE Georgiadis NJ Roca AL Hofreiter M (2010) Mastodon shotgun sequencing Publicly available at the NCBI Short Read Archive (accession no: SRX015822, SRX015823). http://www.ncbi.nlm.nih.gov/sra?term=SRP001730

Cortez D Marin R Toledo-Flores D Froidevaux L Liechti A Waters PD Grützner F Kaessmann H (2013) Origins and functional evolution of Y chromosomes across mammals Publicly available at the NCBI Short Read Archive (accession no: GSM1227965, GSM1227964). http://www.ncbi.nlm.nih.gov/bioproject/PRJNA218629

Reddy PC Sinha I Kelkar A Habib F Pradhan SJ Sukumar R Galande S (2015) Comparative sequence analyses of genome and transcriptome reveal novel transcripts and variants in the Asian elephant Elephas maximus Publicly available at the NCBI Short Read Archive (accession no: SRX1423033). http://www.ncbi.nlm.nih.gov/bioproject/PRJNA301482

Files

elife-11994-v3.pdf

Files (3.9 MB)

Name Size Download all
Article
md5:dcc9f3e475e2a125457a8f234fff8854
3.9 MB Preview Download

Additional details

Identifiers

DOI
10.7554/eLife.11994
Other
oai:uchicago.tind.io:9854

Related works

Is supplement to
https://doi.org/10.7554/eLife.24307 (URL)

Funding

University of Nottingham
Advanced Data Analysis Centre
University of Chicago

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Human Genetics