Inferring Past Environments from Ancient Epigenomes

Gokhman, David; Malul, Anat; Carmel, Liran

doi:10.1093/molbev/msx211

Cited by 52 publications

(39 citation statements)

References 101 publications

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“…Environmentally-induced methylation variation can reflect environmental conditions such as food availability (e.g., Heijmans et al 2008), climate (e.g., Fu et al 2010;Gugger et al 2016), and exposure to disease or toxins (Robertson 2005;Baccarelli and Bollati 2009). Gokhman et al (2017) demonstrated how methylation patterns can be used to study past environments by describing markers of prenatal nutrition in Denisovan and Neanderthal genomes. Ancient and historic epigenomic studies may allow us to explore aspects of past populations that are not reflected in a specimen's morphology or genetic sequence.…”

Section: Applications Of Epigenomic Data From Historic Specimensmentioning

confidence: 99%

“…Around a dozen paleoepigenetic studies have been published to date (Briggs et al 2010;Llamas et al 2012;Gokhman et al 2014;Pedersen et al 2014;Smith et al 2014Smith et al , 2015Orlando and Cooper 2014;Seguin-Orlando et al 2015;Gokhman et al 2016;Hanghøj et al 2016;Gokhman et al 2017;Murphy and Benítez-Burraco 2018). To our knowledge, all previous studies have focused on ancient DNA from paleontological and archaeological specimens rather than "historic DNA" from museum specimens collected by naturalists in the modern era, which range from decades old to a few centuries old.…”

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confidence: 99%

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Museum epigenomics: characterizing cytosine methylation in historic museum specimens

Rubi

Knowles

Dantzer

2019

Preprint

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Museum genomics has transformed the field of collections-based research, opening up a range of new research directions for paleontological specimens as well as natural history specimens collected over the past few centuries. Recent work demonstrates that it is possible to characterize epigenetic markers such as DNA methylation in well-preserved ancient tissues. This approach has not yet been tested in traditionally-prepared natural history specimens such as dried bones and skins, the most common specimen types in vertebrate collections. In this study, we develop and test methods to characterize cytosine methylation in dried skulls up to 76 years old. Using a combination of ddRAD and bisulfite treatment, we characterized patterns of cytosine methylation in two species of deer mouse (Peromyscus spp.) collected in the same region in Michigan in 1940Michigan in , 2003Michigan in , and 2013Michigan in -2016. We successfully estimated methylation in specimens of all age groups, though older specimens yielded less data and showed greater interindividual variation in data yield than newer specimens. Global methylation estimates were reduced in the oldest specimens (76 years old) relative to the newest specimens (1-3 years old), which may reflect post mortem hydrolytic deamination. Methylation was reduced in promoter regions relative to gene bodies and showed greater bimodality in autosomes relative to female X chromosomes, consistent with expectations for methylation in mammalian somatic cells. Our work demonstrates the utility of historic specimens for methylation analyses, as with genomic analyses; however, such studies will need to accommodate the large variance in the quantity of data produced by older specimens.

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Section: Applications Of Epigenomic Data From Historic Specimensmentioning

confidence: 99%

mentioning

confidence: 99%

Museum epigenomics: characterizing cytosine methylation in historic museum specimens

Rubi

Knowles

Dantzer

2019

Preprint

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“…In order to investigate the methylation pattern of PCSK9 in Archaic and modern humans, we downloaded the three whole‐genome bisulfite sequencing bone methylation maps from a chimpanzee and two modern humans, and six reconstructed methylation maps from a Neanderthal, a Denisovan and four ancient modern humans (La Braña, Loschbour, Stuttgart and Ust’‐Ishim) from GEO under accession number: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE96833, as described by Gokhman et al ., .…”

Section: Methodsmentioning

confidence: 99%

Functional analysis of natural PCSK9 mutants in modern and archaic humans

et al. 2019

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PCSK9 is the last member of the proprotein convertases (PCs) family and its gene is mutated in ~ 2% to 3% of individuals with familial hypercholesterolemia (FH). This protein enhances the degradation of the low‐density lipoprotein receptor (LDLR) and hence increases the levels of circulating LDL‐cholesterol (LDLc). Studies of the underlying mechanism(s) regulating the activity of different mutations in the PCSK9 gene are ongoing as they enhance our understanding of the biology and clinical relevance of PCSK9 and its partners. In an attempt to unravel the regulation of PCSK9 transcription and possibly identify mutation ‘hot spot’ regions with alterations in CpG methylation, we present for the first time the complete methylome profile of the PCSK9 gene in modern and archaic humanoids. Our data showed that the genomes of modern humans and archaic PCSK9 exhibit a similar methylation pattern. Next, we defined the mechanistic consequences of three PCSK9 natural mutations (PCSK9‐R96L, ‐R105W, and ‐P174S) and one archaic Denisovan mutation (PCSK9‐H449L) using various complementary cellular and in vitro binding assays. Our results showed that the PCSK9‐H449L is a loss‐of‐function (LOF) mutation, likely due to its lower binding affinity to the LDLR. Similarly, PCSK9‐R96L and ‐R105W are LOF mutations, even though they have been identified in FH patients. The PCSK9‐R105W mutation leads to a significantly lower autocatalytic processing of proPCSK9. PCSK9‐P174S resulted in a LOF in both extracellular and intracellular pathways. In conclusion, our extensive analyses revealed that all studied mutations result in PCSK9 LOF, via various mechanisms, leading to lower levels of LDLc.

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“…Whilst methods to identify epigenetic changes from aDNA are only beginning to be applied (Gokhman et al 2017), and have not currently been used to study Richard, it is possible that the periods of violence and instability he experienced would have had had a lasting effect on his epigenome. For example, witnessing violence as a child has been associated with shortened telomeres (Oliveira et al 2016), as has the death of a father (Mitchell et al 2017), whilst stressful life events in childhood have been associated with hypermethylation (Soares et al 2017).…”

Section: Local Biology Embedded Bodies and Relational Personhood In mentioning

confidence: 99%

Osteobiographies: Local Biologies, Embedded Bodies, and Relational Persons

Appleby

2019

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Osteobiography is an increasingly popular approach, but one that can have the effect of producing unproblematised, individualised approaches to the life course with little theoretical underpinning. In this contribution, I explore what osteobiographies represent. Rather than seeing them as the result of processes and events that happen to skeletons, osteobiographies are produced through the continuing interaction of genes, environment, culture and society over time. These four factors combine to produce osteobiographies that are individualised 'local biologies' (Lock 1993) and which are dynamic across the life course. Drawing on this interaction of the biological and the social, I argue that bone itself emerges out of social action as well as biological processes, and after death acts as a fossilisation of a personhood that is dynamic during life. This concept is drawn out through detailed analysis of the skeleton of King Richard III of England. Isotopic analysis of Richard's skeleton illustrates how his negotiation of his personhood as king caused changes in his lifestyle that altered his bone chemistry. Whilst evidence for increased consumption of high-status food and drink could be interpreted as resulting from increased access to these resources, in fact such consumption was a critical part of his approach to building and maintaining alliances. In this case, the skeleton provides a physiological record of political action.

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Inferring Past Environments from Ancient Epigenomes

Cited by 52 publications

References 101 publications

Museum epigenomics: characterizing cytosine methylation in historic museum specimens

Museum epigenomics: characterizing cytosine methylation in historic museum specimens

Functional analysis of natural PCSK9 mutants in modern and archaic humans

Osteobiographies: Local Biologies, Embedded Bodies, and Relational Persons

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