2024
DOI: 10.1101/2024.02.27.582135
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Rapid evolution of genes with anti-cancer functions during the origins of large bodies and cancer resistance in elephants

Jacob Bowman,
Vincent J. Lynch

Abstract: Elephants have emerged as a model system to study the evolution of body size and cancer resistance because, despite their immense size, they have a very low prevalence of cancer. Previous studies have found that duplication of tumor suppressors at least partly contributes to the evolution of anti-cancer cellular phenotypes in elephants. Still, many other mechanisms must have contributed to their augmented cancer resistance. Here, we use a suite of codon-based maximum-likelihood methods and a dataset of 13,310 … Show more

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Cited by 1 publication
(2 citation statements)
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“…In addition to executing necroptosis, RIPK3 and MLKL mediate NET formation in necroptotic neutrophils, which release NETs at membrane locations surrounded by MLKL (D’Cruz et al, 2018); however, while knockout of RIPK3 and MLKL prevents NET formation it does not prevent cell death because of residual caspase-8 activity (D’Cruz et al, 2018), which is the molecular switch that governs regulated cell death by either apoptosis, necroptosis, or pyroptosis (Fritsch et al, 2019). Remarkably, we previously found that genes related to neutrophil biology were positively selected or rapidly evolving in elephants, including genes that mediate neutrophil extracellular trap formation (Bowman and Lynch, 2024). While neutrophils have well-characterized roles in the innate immune system, they also play an important role in cancer biology, where they can both promote and inhibit tumor initiation, growth, and metastasis (Coffelt et al, 2016).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…In addition to executing necroptosis, RIPK3 and MLKL mediate NET formation in necroptotic neutrophils, which release NETs at membrane locations surrounded by MLKL (D’Cruz et al, 2018); however, while knockout of RIPK3 and MLKL prevents NET formation it does not prevent cell death because of residual caspase-8 activity (D’Cruz et al, 2018), which is the molecular switch that governs regulated cell death by either apoptosis, necroptosis, or pyroptosis (Fritsch et al, 2019). Remarkably, we previously found that genes related to neutrophil biology were positively selected or rapidly evolving in elephants, including genes that mediate neutrophil extracellular trap formation (Bowman and Lynch, 2024). While neutrophils have well-characterized roles in the innate immune system, they also play an important role in cancer biology, where they can both promote and inhibit tumor initiation, growth, and metastasis (Coffelt et al, 2016).…”
Section: Discussionmentioning
confidence: 99%
“…Remarkably, we previously found that genes related to neutrophil biology were positively selected or rapidly evolving in elephants, including genes that mediate neutrophil extracellular trap formation (Bowman and Lynch, 2024). While neutrophils have well-characterized roles in the innate immune system, they also play an important role in cancer biology, where they can both promote and inhibit tumor initiation, growth, and metastasis (Coffelt et al, 2016).…”
Section: Loss Of Net Formation Genes In Paenungulatamentioning
confidence: 99%