scholarly journals TP53copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants

2015 ◽  
Author(s):  
Michael Sulak ◽  
Lindsey Fong ◽  
Katelyn Mika ◽  
Sravanthi Chigurupati ◽  
Lisa Yon ◽  
...  
Keyword(s):  
Dna Damage ◽  
Body Size ◽  
Signaling Pathway ◽  
Copy Number ◽  
Large Body ◽  
Genotoxic Stress ◽  
Suppressor Gene ◽  
Direct Role ◽  
Increased Risk ◽  
Body Sizes

SUMMARYA 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 geneTP53and that the increase inTP53copy 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 theTP53retrogenes (TP53RTGs) are transcribed and likely translated. WhileTP53RTGsdo 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 ofTP53may have played a direct role in the evolution of very large body sizes and the resolution of Peto’s paradox in Proboscideans.

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

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Michael Sulak ◽  
Lindsey Fong ◽  
Katelyn Mika ◽  
Sravanthi Chigurupati ◽  
Lisa Yon ◽  
...  
Keyword(s):  
Dna Damage ◽  
Body Size ◽  
Signaling Pathway ◽  
Copy Number ◽  
Large Body ◽  
Genotoxic Stress ◽  
Suppressor Gene ◽  
Direct Role ◽  
Increased Risk ◽  
Body Sizes

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.

scholarly journals A zombie LIF gene in elephants is up-regulated by TP53 to induce apoptosis in response to DNA damage

2017 ◽  
Author(s):  
Juan Manuel Vazquez ◽  
Michael Sulak ◽  
Sravanthi Chigurupati ◽  
Vincent J. Lynch
Keyword(s):  
Dna Damage ◽  
Body Size ◽  
Cancer Risk ◽  
Leukemia Inhibitory Factor ◽  
Phylogenetic Analyses ◽  
Large Body ◽  
Response Element ◽  
Increased Risk ◽  
Stem Lineage ◽  
Body Sizes

AbstractLarge bodied organisms have more cells that can potentially turn cancerous than smallbodied organisms with fewer cells, imposing an increased risk of developing cancer. This expectation predicts a positive correlation between body size and cancer risk, however, there is no correlation between body size and cancer risk across species (‘Peto’s Paradox’). Here we show that elephants and their extinct relatives (Proboscideans) may have resolved Peto’s Paradox in part through re-functionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro-apoptotic functions. The LIF6 gene is transcriptionally up-regulated by TP53 in response to DNA damage, and translocates to the mitochondria where it induces apoptosis. Phylogenetic analyses of living and extinct Proboscidean LIF6 genes indicates its TP53 response element evolved coincident with the evolution of large body sizes in the Proboscidean stem-lineage. These results suggest that re-functionalizing of a pro-apoptotic LIF pseudogene may have been permissive (though not sufficient) for the evolution of large body sizes in Proboscideans.

scholarly journals Genetic testing of dogs predicts problem behaviors in clinical and nonclinical samples

2020 ◽  
Author(s):  
Isain Zapata ◽  
M. Leanne Lilly ◽  
Meghan E. Herron ◽  
James A. Serpell ◽  
Carlos E. Alvarez
Keyword(s):  
Body Size ◽  
Problem Behaviors ◽  
Small Body ◽  
Community Sample ◽  
Large Body ◽  
Second Phase ◽  
Logistic Regression Models ◽  
Individual Level ◽  
Increased Risk ◽  
Phenotype Data

AbstractVery little is known about the etiology of personality and psychiatric disorders. Because the core neurobiology of many such traits is evolutionarily conserved, dogs present a powerful model. We previously reported genome scans of breed averages of ten traits related to fear, anxiety, aggression and social behavior in multiple cohorts of pedigree dogs. As a second phase of that discovery, here we tested the ability of markers at 13 of those loci to predict canine behavior in a community sample of 397 pedigree and mixed-breed dogs with individual-level genotype and phenotype data. We found support for all markers and loci. By including 122 dogs with veterinary behavioral diagnoses in our cohort, we were able to identify eight loci associated with those diagnoses. Logistic regression models showed subsets of those loci could predict behavioral diagnoses. We corroborated our previous findings that small body size is associated with many problem behaviors and large body size is associated with increased trainability. Children in the home were associated with anxiety traits; illness and other animals in the home with coprophagia; working-dog status with increased energy and separation-related problems; and competitive dogs with increased aggression directed at familiar dogs, but reduced fear directed at humans and unfamiliar dogs. Compared to other dogs, Pit Bull-type dogs were not defined by a set of our markers and were not more aggressive; but they were strongly associated with pulling on the leash. Using severity-threshold models, Pit Bull-type dogs showed reduced risk of owner-directed aggression (75th quantile) and increased risk of dog-directed fear (95th quantile). Our findings have broad utility, including for clinical and breeding purposes, but we caution that thorough understanding is necessary for their interpretation and use.

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

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Michael Sulak ◽  
Lindsey Fong ◽  
Katelyn Mika ◽  
Sravanthi Chigurupati ◽  
Lisa Yon ◽  
...  
Keyword(s):  
Dna Damage ◽  
Body Size ◽  
Dna Damage Response ◽  
Copy Number ◽  
Damage Response

scholarly journals p53 pro-apoptotic activity is regulated by the G2/M promoting factor Cdk1 in response to DNA damage

2021 ◽  
Author(s):  
Mireya Ruiz-Losada ◽  
Raul González ◽  
Ana Peropadre ◽  
Antonio Baonza ◽  
Carlos Estella
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
P53 Protein ◽  
Genotoxic Stress ◽  
Suppressor Gene ◽  
Cell Fate Decisions ◽  
Apoptotic Activity ◽  
Induced Apoptosis

SummaryExposure to genotoxic stress promotes cell-cycle arrest and DNA repair or apoptosis. These “life” or “death” cell fate decisions often rely on the activity of the tumor suppressor gene p53. Therefore, how p53 activity is precisely regulated is essential to maintain tissue homeostasis and to prevent cancer development. Here we demonstrate that Drosophila p53 pro-apoptotic activity is regulated by the G2/M kinase Cdk1. We find that cell cycle arrested or endocycle-induced cells are refractory to ionizing radiation induced apoptosis. We show that the p53 protein is not able to bind to and to activate the expression of the pro-apoptotic genes in experimentally arrested cells. Our results indicate that p53 genetically and physically interacts with Cdk1 and that p53 pro-apoptotic role is regulated by the cell cycle status of the cell. We propose a model in which cell cycle progression and p53 pro-apoptotic activity are molecularly connected to coordinate the appropriate response after DNA damage.

scholarly journals Size- and sex-specific predation on dung flies by amphibian and arthropod predators – size match matters

2019 ◽  
Author(s):  
Wolf U. Blanckenhorn ◽  
Gabriele Cozzi ◽  
Gregory Jäggli ◽  
Juan Pablo Busso
Keyword(s):  
Body Size ◽  
Sexual Size Dimorphism ◽  
Rana Temporaria ◽  
Large Body ◽  
Mechanistic Study ◽  
Mating Activity ◽  
Size Dimorphism ◽  
Arthropod Predators ◽  
Body Sizes ◽  
Predation Rates

Because predator-prey interactions in nature are multifarious, linking phenomenological predation rates to the underlying behavioural or ecological mechanisms is challenging. Size- and sex-specific predation has been implicated as a major selective force keeping animals small, affecting the evolution of body size and sexual size dimorphism. We experimentally assessed predation by various amphibian (frogs and toads) and arthropod predators (bugs, flies, spiders) on three species of dung flies with similar ecology but contrasting body sizes, sexual size dimorphism and coloration. Predators were offered a size range of flies in single- or mixed-sex groups. As expected based on optimal foraging theory, some anurans (e.g. Bufo bufo) selected larger prey, thus selecting against large body size of the flies, while others (Bombina variagata and Rana esculenta) showed no such pattern. Small juvenile Rana temporaria metamorphs, in contrast, preferred small flies, as did all arthropod predators, a pattern that can be explained by larger prey being better at escaping. The more mobile males were not eaten more frequently or faster than the cryptic females, even when conspicuously colored. Predation rates on flies in mixed groups permitting mating activity were not higher, contrary to expectation, nor was predation generally sex-specific. We conclude that the size-selectivity of predators, and hence the viability selection pattern exerted on their prey, depends foremost on the relative body sizes of the two in a continuous fashion. Sex-specific predation by single predators appears to contribute little to sexual dimorphism. Therefore, the mechanistic study of predation requires integration of both the predator’s and the prey’s perspectives, and phenomenological field studies of predation remain indispensable.

scholarly journals Sam68/KHDRBS1 is critical for colon tumorigenesis by regulating genotoxic stress-induced NF-κB activation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kai Fu ◽  
Xin Sun ◽  
Eric M Wier ◽  
Andrea Hodgson ◽  
Yue Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dna Damage ◽  
Signaling Pathway ◽  
Rna Binding ◽  
Genotoxic Stress ◽  
Human Colon ◽  
Tumor Burden ◽  
Human Colon Cancer ◽  
Nuclear Signaling ◽  
Colon Tumorigenesis

Nuclear factor kappa B (NF-κB)-mediated transcription is an important mediator for cellular responses to DNA damage. Genotoxic agents trigger a 'nuclear-to-cytoplasmic' NF-κB activation signaling pathway; however, the early nuclear signaling cascade linking DNA damage and NF-κB activation is poorly understood. Here we report that Src-associated-substrate-during-mitosis-of-68kDa/KH domain containing, RNA binding, signal transduction associated 1 (Sam68/KHDRBS1) is a key NF-κB regulator in genotoxic stress-initiated signaling pathway. Sam68 deficiency abolishes DNA damage-stimulated polymers of ADP-ribose (PAR) production and the PAR-dependent NF-κB transactivation of anti-apoptotic genes. Sam68 deleted cells are hypersensitive to genotoxicity caused by DNA damaging agents. Upregulated Sam68 coincides with elevated PAR production and NF-κB-mediated anti-apoptotic transcription in human and mouse colon cancer. Knockdown of Sam68 sensitizes human colon cancer cells to genotoxic stress-induced apoptosis and genetic deletion of Sam68 dampens colon tumor burden in mice. Together our data reveal a novel function of Sam68 in the genotoxic stress-initiated nuclear signaling, which is crucial for colon tumorigenesis.

“She was neither unduly fat nor lanky”: Representation of body size and beauty in the novels of Daniel O. Fágúnwà

2020 ◽  
Vol 18 (1) ◽  
pp. 131-147
Author(s):  
Fausat Motunrayo Ibrahim ◽  
Ayodele S. Jegede
Keyword(s):  
Body Size ◽  
Large Body ◽  
African Literature ◽  
Thin Structure ◽  
Self Worth ◽  
Body Sizes ◽  
Definition Of

The climate of thought regarding beauty characterization among Africans and other people of colour portrays the large body as beautiful. This reflects that body size and beauty is racially and culturally expressive, making it apposite to be disparate in advancing related discourses. This is particularly important because such discourses can influence Africans’ evaluation of their self-worth. The concerns generated by the global rise in obesity further create interest in these issues. African literature offers a fine and disparate platform to understand social realities. Consequently, relevant contents of the five precedent Yorùbá novels of Daniel Fágúnwà including Igbó Olódùmarè, Ìrèké Oníbùdó,Ògbójú ọdẹ nínú Igbó Irúnmọlè, Ìrìnkèrindò nínú Igbó Elégbèje and Àdììtú Olódùmarè were extracted and analyzed to examine association of beauty with body sizes. Findings reflect more of bipolarity in the definition of beauty, such that the none-fat/none-thin structure is conveyed as beautiful. Concurrently, the fat and the thin is also portrayed as beautiful, making ‘body size’ definition of beauty to be elusive, and strongly suggesting neutrality to body size among the Yorùbá. This is strongly borne out of Fágúnwà’s and indeed, Yorùbá construction of beauty from a ‘character’ perspective. Character (ìwà) is staunchly expounded as constituting beauty. The beautiful body size is indeterminate in Fágúnwà’s narratives and indeed, in Yorùbá thought.

Prey preference of a wasp determined by nest size supports the role of natural selection in body size evolution in Cassidinae leaf beetles

2021 ◽  
Author(s):  
Tadashi Shinohara ◽  
Yasuoki Takami
Keyword(s):  
Body Size ◽  
Natural Selection ◽  
Prey Species ◽  
Large Body ◽  
Size Variation ◽  
Prey Preference ◽  
Nest Size ◽  
Large Prey ◽  
Leaf Beetles ◽  
Body Sizes

Abstract The prey preference of a predator can impose natural selection on prey phenotypes, including body size. Despite evidence that large body size protects against predation in insects, the determinants of body size variation in Cassidinae leaf beetles are not well understood. We examined the prey preference of the digger wasp Cerceris albofasciata, a specialist predator of adult Cassidinae leaf beetles, and found evidence for natural selection on prey body size. The wasp hunted prey smaller than the size of their nest entrance. However, the wasp preferred larger prey species among those that could be carried into their nest. Thus, the benefits of large prey and the cost associated with nest expansion might determine the prey size preference. As expected from the prey species preference, the wasp preferred small individuals of the largest prey species, Thlaspida biramosa, and large individuals of the smallest prey species, Cassida piperata, resulting in natural selection on body sizes. In intermediate-sized prey species, however, there was no evidence for selection on body size. Natural selection on body size might explain the variation of prey morphologies that increase body size, such as explanate margins, in this group.

Traditional Attenuation of Inequality: Neutral Meaning of Body Size among the Yorùbá of Southwestern Nigeria

2020 ◽  
pp. 1-25
Author(s):  
Fausat M. Ibrahim ◽  
Ayodele S. Jegede
Keyword(s):  
Body Size ◽  
Phenomenological Study ◽  
Large Body ◽  
Human Person ◽  
Group Discussions ◽  
Southwestern Nigeria ◽  
Good Person ◽  
Body Sizes ◽  
Globalized World ◽  
Depth Interviews

Abstract Body size is a profound ground of inequality in modern global society. Moreover, constructions of body size are racially polarized, with blacks being reputed for venerating large body. Proceeding with a triangulation of qualitative methods, this phenomenological study featured forty-two in-depth interviews, eight focus group discussions and eighteen key informant interviews among men and women of varying body sizes in two of the six states of southwestern Nigeria. Findings reflect dominantly neutral meaning of body size among the Yorùbá. This neutrality is dominantly reflected in the literal questioning of meaning that Yorùbá attach to body size, and who becomes a king in Yorùbá land but partially neutral in acceptability of prospective son or daughter in-law. Divinity, orí (fate), ìwà (good behavior) and ọmọlúàbí (good person) are among phenomena that counts in discerning people’s worth. Meaning attached to body size is opposed to common-place attitude to body size, making this attitude to be profane while meaning is solemn. This meaning is tremendously in favour of optimum health, and attenuating inequality, for which even black societies are perpetrating in the globalized world. Traditional Yorùbá value of human person is irrespective of body size.

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