Comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates

Swain-Lenz, Devjanee; Berrío, Alejandro; Safi, Alexias; Crawford, Gregory E.; Wray, Gregory A.

doi:10.1101/524868

Cited by 3 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Swain- Lenz et al (2019) performed comparative analyses of the adipose chromatin landscape in humans, chimpanzees, and rhesus macaques, concluding that their findings reflect differences in the adapted diets of humans and chimpanzees. They (p. 2004) write:…”

Section: Genetic and Metabolic Adaptation To High-fat Dietmentioning

confidence: 99%

“…Swain‐Lenz et al (2019) performed comparative analyses of the adipose chromatin landscape in humans, chimpanzees, and rhesus macaques, concluding that their findings reflect differences in the adapted diets of humans and chimpanzees. They (p. 2004) write: “Taken together, these results suggest that humans shut down regions of the genome to accommodate a high‐fat diet while chimpanzees open regions of the genome to accommodate a high sugar diet.”…”

Section: Physiological Evidencementioning

confidence: 99%

See 1 more Smart Citation

The evolution of the human trophic level during the Pleistocene

Ben-Dor

Sirtoli

Barkai

2021

American J Phys Anthropol

View full text Add to dashboard Cite

The human trophic level (HTL) during the Pleistocene and its degree of variability serve, explicitly or tacitly, as the basis of many explanations for human evolution, behavior, and culture. Previous attempts to reconstruct the HTL have relied heavily on an analogy with recent hunter-gatherer groups' diets. In addition to technological differences, recent findings of substantial ecological differences between the Pleistocene and the Anthropocene cast doubt regarding that analogy's validity. Surprisingly little systematic evolution-guided evidence served to reconstruct HTL. Here, we reconstruct the HTL during the Pleistocene by reviewing evidence for the impact of the HTL on the biological, ecological, and behavioral systems derived from various existing studies. We adapt a paleobiological and paleoecological approach, including evidence from human physiology and genetics, archaeology, paleontology, and zoology, and identified 25 sources of evidence in total. The evidence shows that the trophic level of the Homo lineage that most probably led to modern humans evolved from a low base to a high, carnivorous position during the Pleistocene, beginning with Homo habilis and peaking in Homo erectus. A reversal of that trend appears in the Upper Paleolithic, strengthening in the Mesolithic/Epipaleolithic and Neolithic, and culminating with the advent of agriculture. We conclude that it is possible to reach a credible reconstruction of the HTL without relying on a simple analogy with recent hunter-gatherers' diets. The memory of an adaptation to a trophic level that is embedded in modern humans' biology in the form of genetics, metabolism, and morphology is a fruitful line of investigation of past HTLs, whose potential we have only started to explore.

show abstract

Section: Genetic and Metabolic Adaptation To High-fat Dietmentioning

confidence: 99%

Section: Physiological Evidencementioning

confidence: 99%

The evolution of the human trophic level during the Pleistocene

Ben-Dor

Sirtoli

Barkai

2021

American J Phys Anthropol

View full text Add to dashboard Cite

show abstract

“…While gene expression divergence has been extensively characterized in mammalian tissues (Brawand et al, 2011;Cardoso-Moreira et al, 2019), the evolution of the associated regulatory regions is not well understood. Enhancer and promoter evolution has mostly been studied by comparing one mammalian tissue or cell type across several species (Danko et al, 2018;Glinsky and Barakat, 2019;Swain-Lenz et al, 2019;Villar et al, 2015). This approach is unable to compare evolutionary trends across tissues.…”

Section: Introductionmentioning

confidence: 99%

LINE elements are a reservoir of regulatory potential in mammalian genomes

Roller

Stamper

Villar

et al. 2020

Preprint

View full text Add to dashboard Cite

To investigate the mechanisms driving regulatory evolution across tissues, we experimentally mapped promoters, enhancers, and gene expression in liver, brain, muscle, and testis from ten diverse mammals. The regulatory landscape around genes included both tissue-shared and tissue-specific regulatory regions, where tissue-specific promoters and enhancers evolved 5 most rapidly. Genomic regions switching between promoters and enhancers were more common across species, and less common across tissues within a single species. Long Interspersed Nuclear Elements (LINEs) played recurrent evolutionary roles: LINE L1s were associated with tissue-specific regulatory regions, whereas more ancient LINE L2s were associated with tissue-shared regulatory regions and with those switching between promoter 10 and enhancer signatures across species. Our analyses of the tissue-specificity and evolutionary stability among promoters and enhancers reveal how specific LINE families have helped shape the dynamic mammalian regulome. HIGHLIGHTS 15• Tissue-specific regulatory regions evolve faster than tissue-shared • Switching promoter and enhancer regulatory roles is frequent in evolution • LINE L1s contribute to the evolution of tissue-specific regulatory regions • LINE L2s are associated with broad tissue activity and dynamic regulatory signatures 20

show abstract

“…These results indicate metabolic phenotypic differences among mammals with human lineage-specific acceleration of fat-associated endurance. To assess lineage-specific molecular signatures between humans and primates, we compared transcriptomic and epigenomic data from organs with high fat content such as brain and adipose tissue (26,27), followed by functional annotation in tissue-specific networks (28). Consistent with phenotypic data, homo sapiens displayed enhanced transcriptional regulatory mechanisms and decreased lipid degradation (Fig.…”

Section: Phenotypic and Molecular Adaptations Reveal Metabolic Human Acceleration Domainsmentioning

confidence: 84%

“…(C) Network-derived discovery of biological processes (28) in human enriched gene sets from tissues with high-fat content. Data derived from differential expression by RNAseq and ATACseq comparing human and primate tissues (26,27). (D) Network-based node prioritization of recomposed interacting transcriptional regulators binding to HAR-associated genes.…”

Section: Phenotypic and Molecular Adaptations Reveal Metabolic Human Acceleration Domainsmentioning

confidence: 99%

Metabolic resilience is encoded in genome plasticity

Agudelo

Tuyéras

Llinares

et al. 2021

Preprint

View full text Add to dashboard Cite

Metabolism plays a central role in evolution, as resource conservation is a selective pressure for fitness and survival. Resource-driven adaptations offer a good model to study evolutionary innovation more broadly. It remains unknown how resource-driven optimization of genome function integrates chromatin architecture with transcriptional phase transitions. Here we show that tuning of genome architecture and heterotypic transcriptional condensates mediate resilience to nutrient limitation. Network genomic integration of phenotypic, structural, and functional relationships reveals that fat tissue promotes organismal adaptations through metabolic acceleration chromatin domains and heterotypic PGC1A condensates. We find evolutionary innovation in several dimensions; low conservation of amino acid residues within protein disorder regions, nonrandom chromatin location of metabolic acceleration domains, condensate-chromatin stability through cis-regulatory archoring and encoding of genome plasticity in radial chromatin organization. We show that environmental tuning of these adaptations leads to fasting endurance, through efficient nuclear compartmentalization of lipid metabolic regions, and, locally, human-specific burst kinetics of lipid cycling genes. This process reduces oxidative stress, and fatty-acid mediated cellular acidification, enabling endurance of condensate chromatin conformations. Comparative genomics of genetic and diet perturbations reveal mammalian convergence of phenotype and structural relationships, along with loss of transcriptional control by diet-induced obesity. Further, we find that radial transcriptional organization is encoded in functional divergence of metabolic disease variant-hubs, heterotypic condensate composition, and evolutionary tuned protein residues sensing metabolic variation. During fuel restriction, these features license the formation of large heterotypic condensates that buffer proton excess, and shift viscoelasticity for condensate endurance. This mechanism maintains physiological pH, reduces pH-resilient inflammatory gene programs, and enables genome plasticity through transcriptionally driven cell-specific chromatin contacts. In vivo manipulation of this circuit promotes fasting-like adaptations with heterotypic nuclear compartments, metabolic and cell-specific homeostasis. In sum, we uncover here a general principle by which transcription uses environmental fluctuations for genome function, and demonstrate how resource conservation optimizes transcriptional self-organization through robust feedback integrators, highlighting obesity as an inhibitor of genome plasticity relevant for many diseases.

show abstract

Comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates

Cited by 3 publications

References 39 publications

The evolution of the human trophic level during the Pleistocene

The evolution of the human trophic level during the Pleistocene

LINE elements are a reservoir of regulatory potential in mammalian genomes

Metabolic resilience is encoded in genome plasticity

Contact Info

Product

Resources

About