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

Sulak, Michael; Fong, Lindsey; Mika, Katelyn; Chigurupati, Sravanthi; Yon, Lisa; Mongan, Nigel P.; Emes, Richard D.; Lynch, Vincent J.

doi:10.7554/elife.11994

Cited by 235 publications

(352 citation statements)

References 87 publications

(119 reference statements)

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“…However, no correlation between body size or lifespan and the occurrence of cancer can be found [250,251,252]. Interestingly, elephants possess 20 copies of the p53 gene and show a hyperactive p53-dependent DNA damage response, potentially contributing to cancer resistance in this large, long-lived animal [253]. …”

Section: Ploidy Aberrations and P53mentioning

confidence: 99%

The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis

Potapova

Gorbsky

2017

Biology

159

116

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Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.

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Section: Ploidy Aberrations and P53mentioning

confidence: 99%

The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis

Potapova

Gorbsky

2017

Biology

159

116

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“…which implies an evolutionary selective trend in the increased number of copies of TP53 in the genomes of these related megafauna (Sulak et al, 2016). TP53 is considered the guardian of the genome due to its role in mitigating DNA damage, and is itself a target of UV-induced mutations (Aylon & Oren, 2011;de Pedro et al, 2018).…”

Section: Reviews Of Geophysicsmentioning

confidence: 99%

The Role of Geomagnetic Field Intensity in Late Quaternary Evolution of Humans and Large Mammals

Channell

Vigliotti

2019

Reviews of Geophysics

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It has long been speculated that biological evolution was influenced by ultraviolet radiation (UVR) reaching the Earth's surface, despite imprecise knowledge of the timing of both UVR flux and evolutionary events. The past strength of Earth's dipole field provides a proxy for UVR flux because of its role in maintaining stratospheric ozone. The timing of Quaternary evolutionary events has become better constrained by fossil finds, improved radiometric dating, use of dung fungi as proxies for herbivore populations, and improved ages for nodes in human phylogeny from human mitochondrial DNA and Y chromosomes. The demise of Neanderthals at ~41 ka can now be closely tied to the intensity minimum associated with the Laschamp magnetic excursion, and the survival of anatomically modern humans can be attributed to differences in the aryl hydrocarbon receptor that has a key role in the evolutionary response to UVR flux. Fossil occurrences and dung‐fungal proxies in Australia indicate that episodes of Late Quaternary extinction of mammalian megafauna occurred close to the Laschamp and Blake magnetic excursions. Fossil and dung fungal evidence for the age of the Late Quaternary extinction in North America (and Europe) coincide with a prominent decline in geomagnetic field intensity at ~13 ka. Over the last ~200 kyr, phylogeny based on mitochondrial DNA and Y chromosomes in modern humans yields nodes and bifurcations in evolution corresponding to geomagnetic intensity minima, which supports the proposition that UVR reaching Earth's surface influenced mammalian evolution with the loci of extinction controlled by the geometry of stratospheric ozone depletion.

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“…Here we assume cancer cells require at least one adaptive trait for survival (e.g. anti-apoptotic or metabolism related traits) as also inspired by microbial adaptive evolution 61 and mammals with very low cancer incidencies 62,63 . For simplicity we set the number of traits, (the dimensionality of the fitness landscape), in each simulation unless otherwise stated.…”

Section: Sudden Change In the Phenotypic Optimummentioning

confidence: 99%

Why is cancer not more common? A changing microenvironment may help to explain why, and suggests strategies for anti-cancer therapy

Jiang

Tomlinson

2018

Preprint

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AbstractOne of the great unsolved puzzles in cancer biology is not why cancers occur, but rather, explaining why so few cancers occur compared with the theoretical number that could occur given the number of progenitor cells in the body and the normal mutation rate. We hypothesised that a contributory explanation is that the tumour microenvironment (TME) is not fixed, and that this could impair the ability of neoplastic cells to retain a high enough fitness to become a cancer. The TME has implicitly been assumed to be static in most cancer evolution models, and we therefore developed a mathematical model of spatial cancer evolution assuming that the TME, and thus the optimum cancer phenotype, change over time. Based on simulations, we show how cancer cell populations adapt to diverse changing TME conditions and fitness landscapes. Compared with static TMEs which generate neutral dynamics, changing TMEs lead to complex adaptations with spatio-temporal heterogeneity involving variable sub-clonal fitness, mixing, competition and phylogeny patterns. In many cases, cancer cell populations fail to grow or undergo spontaneous regression, and even extinction. Our analyses predict that cancer evolution in a changing TME is challenging, and can help to explain why cancer is neither inevitable nor as common as expected. Should cancer driver mutations with effects dependent of the TME exist, they are likely to be selected. Anti-cancer prevention and treatment strategies based on changing the TME are feasible and potentially effective.

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

Cited by 235 publications

References 87 publications

The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis

The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis

The Role of Geomagnetic Field Intensity in Late Quaternary Evolution of Humans and Large Mammals

Why is cancer not more common? A changing microenvironment may help to explain why, and suggests strategies for anti-cancer therapy

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