Novel Genomic Insights into Body Size Evolution in Cetaceans and a Resolution of Peto’s Paradox

Sun, Di; Chai, Simin; Huang, Xin; Wang, Yingying; Xiao, Linlin; Xu, Shixia; Yang, Guang

doi:10.1086/717768

Cited by 15 publications

(9 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The low, flat cancer risk of other vertebrates with lifespans and body size equal to or exceeding that of our species-for example elephants [14] and whales [15]-demonstrates that cancer risk is aberrant in humans (Figure 2). This disparity recently helped to uncover an equation linking lifetime cancer risk (R) to evolutionary variables associated with speciation, including body size (S), lifespan (Li), species-specific mechanism of tumor suppression (T), and carcinogen exposure (E), such that in order for the process of speciation to include an increase in body size, an equilibrating "improvement" in tumor suppression mechanism for the new species must occur, in order to keep R at the value of the ancestral species, ≤ 5% (Figure 3, and graphical abstract).…”

Section: The Lex Naturalis Equation Links Speciation To Lifetime Canc...mentioning

confidence: 86%

“…Recent results now indicate that every vertebrate species has evolved its own, unique, species-specific mechanism of tumor suppression [14,15,[11][12][13]. As is evident by comparative cancer research, evolution by natural selection has evolved a general rule that a certain low amount of neoplastic transformation is enabled in vertebrate animals, probably because a certain low amount of genomic instability is required so that the process of speciation can respond to changes in the environment, or exploit new opportunities.…”

Section: The Lex Naturalis Equation Links Speciation To Lifetime Canc...mentioning

confidence: 99%

See 1 more Smart Citation

The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens

Nyce¹

2023

Preprint

View full text Add to dashboard Cite

Adrenarche is a developmental phase that occurs only in humans and chimpanzees. It is characterized by the maturation of the adrenal zona reticularis, culminating in the synthesis and secretion of enormous amounts of dehydroepiandro-sterone sulfate (DHEAS) into the blood stream. The purpose of adrenarche, and the flooding of the circulation with DHEAS in the period preceding the onset of adult human body size, has been described as “enigmatic.” This laboratory has uncovered a previously unknown, human-specific “kill-switch” tumor suppression mechanism in which circulating DHEAS is pumped into cells that have undergone tumorigenic mutation(s)— primarily in the TP53 tumor suppressor gene. We refer to such tumorigenic single cells as singularities. The advantage of eliminating tumorigenic cells while they are still in their single cell state, before they have evolved into the heterogeneous tumor cell populations that have proven refractory to chemotherapeutic sterilization, is obvious. This is accomplished by activation of the kill-switch in singularities by de-sulfating imported DHEAS to dehydroepiandrosterone (DHEA), a potent uncompetitive inhibitor of the enzyme Glucose-6-phosphate Dehydrogenase (G6PD). G6PD is responsible for the production of most of the NADPH required for the synthesis and maintenance of activity of anti-oxidant selenoproteins, and for the ubiquinol that prevents ferroptosis. In singularities, uncompetitive inhibition of G6PD by DHEA rapidly becomes irreversible, leading to ROS/ferroptosis-mediated cell death.

show abstract

Section: The Lex Naturalis Equation Links Speciation To Lifetime Canc...mentioning

confidence: 86%

Section: The Lex Naturalis Equation Links Speciation To Lifetime Canc...mentioning

confidence: 99%

The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens

Nyce¹

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Analyzing the molecular mechanisms underlying size variation in groupers is crucial for understanding the causal relationship between longevity and body size, and it is essential for deciphering the driving factors of lifespan regulation. Inflammation, ribosomes, DNA damage, and protein degradation are associated with lifespan ( Sun et al, 2022 ; Tyshkovskiy et al, 2023 ). Inflammation is considered a crucial hallmark of aging, and evolutionary strategies that minimize inflammation are beneficial for longevity ( Tyshkovskiy et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic mechanism of body size variation in groupers: Insights from phylotranscriptomics

Zhang,

Weng,

Wang

et al. 2024

Zoological Research

View full text Add to dashboard Cite

Animal body size variation is of particular interest in evolutionary biology, but the genetic basis remains largely unknown. Previous studies have shown the presence of two parallel evolutionary genetic clusters within the fish genus Epinephelus with evident divergence in body size, providing an excellent opportunity to investigate the genetic basis of body size variation in vertebrates. Herein, we performed phylotranscriptomic analysis and reconstructed the phylogeny of 13 epinephelids originating from the South China Sea. Two genetic clades with an estimated divergence time of approximately 15.4 million years ago were correlated with large and small body size, respectively. A total of 180 rapidly evolving genes and two positively selected genes were identified between the two groups. Functional enrichment analyses of these candidate genes revealed distinct enrichment categories between the two groups. These pathways and genes may play important roles in body size variation in groupers through complex regulatory networks. Based on our results, we speculate that the ancestors of the two divergent groups of groupers may have adapted to different environments through habitat selection, leading to genetic variations in metabolic patterns, organ development, and lifespan, resulting in body size divergence between the two locally adapted populations. These findings provide important insights into the genetic mechanisms underlying body size variation in groupers and species differentiation.

show abstract

“…We included species relevant for our study such as whales and elephants due to a link between large body size and cancer resistance [29][30][31] and bats or naked mole rat as animals with a special immune system [32,33]. Altogether, we collected 294 protein sequences from 63 species (electronic supplementary material, table S3).…”

Section: P38 Evolution In Vertebratesmentioning

confidence: 99%

Evolutionary analysis of p38 stress-activated kinases in unicellular relatives of animals suggests an ancestral function in osmotic stress

et al. 2023

View full text Add to dashboard Cite

p38 kinases are key elements of the cellular stress response in animals. They mediate the cell response to a multitude of stress stimuli, from osmotic shock to inflammation and oncogenes. However, it is unknown how such diversity of function in stress evolved in this kinase subfamily. Here, we show that the p38 kinase was already present in a common ancestor of animals and fungi. Later, in animals, it diversified into three JNK kinases and four p38 kinases. Moreover, we identified a fifth p38 paralog in fishes and amphibians. Our analysis shows that each p38 paralog has specific amino acid substitutions around the hinge point, a region between the N-terminal and C-terminal protein domains. We showed that this region can be used to distinguish between individual paralogs and predict their specificity. Finally, we showed that the response to hyperosmotic stress in Capsaspora owczarzaki , a close unicellular relative of animals, follows a phosphorylation–dephosphorylation pattern typical of p38 kinases. At the same time, Capsaspora 's cells upregulate the expression of GPD1 protein resembling an osmotic stress response in yeasts. Overall, our results show that the ancestral p38 stress pathway originated in the root of opisthokonts, most likely as a cell's reaction to salinity change in the environment. In animals, the pathway became more complex and incorporated more stimuli and downstream targets due to the p38 sequence evolution in the docking and substrate binding sites around the hinge region. This study improves our understanding of p38 evolution and opens new perspectives for p38 research.

show abstract

Novel Genomic Insights into Body Size Evolution in Cetaceans and a Resolution of Peto’s Paradox

Cited by 15 publications

References 102 publications

The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens

The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens

Genetic mechanism of body size variation in groupers: Insights from phylotranscriptomics

Evolutionary analysis of p38 stress-activated kinases in unicellular relatives of animals suggests an ancestral function in osmotic stress

Contact Info

Product

Resources

About