Reconstruction of evolutionary changes in fat and toxin consumption reveals associations with gene losses in mammals: A case study for the lipase inhibitor <i>PNLIPRP1</i> and the xenobiotic receptor <i>NR1I3</i>

Wagner, Franziska; Ruf, Irina; Lehmann, Thomas; Hofmann, Rainer; Ortmann, Sylvia; Schiffmann, Christian; Hiller, Michael; Stefen, Clara; Stuckas, Heiko

doi:10.1111/jeb.13970

Cited by 8 publications

(5 citation statements)

References 65 publications

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“…Matthew J. Christmas 1, † , Irene M. Kaplow 2,3, † , Diane P. Genereux 4 , Michael X. Dong 1 , Graham M. Hughes 5 , Xue Li 4,6,7 , Patrick F. Sullivan 8,9 , Allyson G. Hindle 10 , Gregory Andrews 7 , Joel C. Armstrong 11 , Matteo Bianchi 1 , Ana M. Breit 12 , Mark Diekhans 11 , Cornelia Fanter 10 , Nicole M. Foley 13 , Daniel B. Goodman 14 , Linda Goodman 15 , Kathleen C. Keough 15,16,17 , Bogdan Kirilenko 18,19,20 , Amanda Kowalczyk 2,3 , Colleen Lawless 5 , Abigail L. Lind 16,17…”

Section: Authorsmentioning

confidence: 99%

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Evolutionary constraint and innovation across hundreds of placental mammals

Christmas

Kaplow

Genereux

et al. 2023

Science

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Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth’s vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.

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Section: Authorsmentioning

confidence: 99%

“…Previous studies have used comparative genomics analyses to associate protein-coding changes with specific adaptations (16), such as diet type (17), echolocation (18), and subterranean habitation (19). However, these studies included few species relative to Zoonomia.…”

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confidence: 99%

Evolutionary constraint and innovation across hundreds of placental mammals

Christmas

Kaplow

Genereux

et al. 2023

Science

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“…Novel TCPOBOP-induced genes of special interest include Pnliprp1 and Fzd10 , whose expression increased >90-100-fold in both sexes, both 1 d and 2 wk after a single TCPOBOP injection. Pnliprp1 is a metabolic inhibitor of triglyceride digestion whose expression is positively associated with diets rich in high fat intake across species [70, 71]. Fzd10 is a plasma membrane receptor whose signaling activates beta-catenin and Yap1.…”

Section: Resultsmentioning

confidence: 99%

Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: Primary and secondary gene responses with links to disease progression

Sonkar,

Ma,

Waxman

2024

Preprint

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Constitutive Androstane Receptor (CAR,Nr1i3), a liver nuclear receptor and xenobiotic sensor, induces drug, steroid and lipid metabolizing enzymes, stimulates liver hypertrophy and hyperplasia, and ultimately, hepatocellular carcinogenesis. The mechanisms linking early CAR responses to subsequent disease development are poorly understood. Here we show that exposure of CD-1 mice to TCPOBOP, a halogenated xenochemical and selective CAR agonist ligand, induces pericentral steatosis marked by hepatic accumulation of cholesterol and neutral lipid, and elevated circulating alanine aminotransferase levels, indicating hepatocyte damage. TCPOBOP-induced steatosis was weaker in the pericentral region but stronger in the periportal region in females compared to males. Early (1-day) TCPOBOP transcriptional responses were enriched for CAR-bound primary response genes, and for lipid and xenobiotic metabolism and oxidative stress protection pathways; late (2-wk) TCPOBOP responses included many CAR binding-independent secondary response genes, with enrichment for immune response, macrophage activation, and cytokine and reactive oxygen species production. Late upstream regulators specific to TCPOBOP-exposed male liver were linked to pro-inflammatory responses and hepatocellular carcinoma progression. TCPOBOP administered weekly to male mice using a high corn oil vehicle activated carbohydrate-responsive transcription factor (MLXIPL)-regulated target genes, dysregulated mitochondrial respiratory and translation regulatory pathways, and induced more advanced liver pathology. Thus, TCPOBOP exposure recapitulates histological and gene expression changes characteristic of emerging steatotic liver disease, including secondary expression changes in liver non-parenchymal cells indicative of transition to a more advanced disease state. Upstream regulators of both the early and late TCPOBOP gene responses include novel biomarkers for foreign chemical-induced metabolic dysfunction-associated steatotic liver disease.

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“…Previous comparative genomic work on cave-dwelling and fossorial lineages with eye degradation has provided vital insights into the genetic basis of eye-related gene function and disease [15][16][17]. In addition, insights from genomic studies of gene loss have been critical to informing convergent adaptive function [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Gene loss and relaxed selection of plaat1 in vertebrates adapted to low-light environments

Drabeck,

Wiese,

Gilbertson

et al. 2024

Proc. R. Soc. B.

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Gene loss is an important mechanism for evolution in low-light or cave environments where visual adaptations often involve a reduction or loss of eyesight. The plaat gene family encodes phospholipases essential for the degradation of organelles in the lens of the eye. These phospholipases translocate to damaged organelle membranes, inducing them to rupture. This rupture is required for lens transparency and is essential for developing a functioning eye. Plaat3 is thought to be responsible for this role in mammals, while plaat1 is thought to be responsible in other vertebrates. We used a macroevolutionary approach and comparative genomics to examine the origin, loss, synteny and selection of plaat1 across bony fishes and tetrapods. We showed that plaat1 (probably ancestral to all bony fish + tetrapods) has been lost in squamates and is significantly degraded in lineages of low-visual-acuity and blind mammals and fishes. Our findings suggest that plaat1 is important for visual acuity across bony vertebrates, and that its loss through relaxed selection and pseudogenization may have played a role in the repeated evolution of visual systems in low-light environments. Our study sheds light on the importance of gene-loss in trait evolution and provides insights into the mechanisms underlying visual acuity in low-light environments.

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Reconstruction of evolutionary changes in fat and toxin consumption reveals associations with gene losses in mammals: A case study for the lipase inhibitor PNLIPRP1 and the xenobiotic receptor NR1I3

Cited by 8 publications

References 65 publications

Evolutionary constraint and innovation across hundreds of placental mammals

Evolutionary constraint and innovation across hundreds of placental mammals

Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: Primary and secondary gene responses with links to disease progression

Gene loss and relaxed selection of plaat1 in vertebrates adapted to low-light environments

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