Genomic Imprinting of Grb10 : Coadaptation or Conflict?

Wilkins, Jon F.

doi:10.1371/journal.pbio.1001800

Cited by 10 publications

(6 citation statements)

References 35 publications

(32 reference statements)

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“…5 and ). It is, therefore, important to keep in mind that the presence of variation is necessarily a key factor in driving the coadaptation process (Haig ; Wilkins ; Ubeda and Gardner ), and hence processes that generate or maintain variation are likely to be important determinants of the types of traits and scenarios where coadaptation will be important. Our model makes no assumptions about the processes that introduce or maintain this variation (and it is outside the scope of our analysis) but the general conditions where our model applies may be broad given that most traits examined in natural populations show genetic variation, including traits that mediate the outcome of social interactions among conspecifics (e.g., Hunt and Simmons ; Wilson et al ).…”

Section: Resultsmentioning

confidence: 99%

The coadaptation theory for genomic imprinting

O’Brien

Wolf

2017

Evolution Letters

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Imprinted genes are peculiar in that expression of the two copies differs depending on whether the copy was maternally or paternally inherited. The discovery of this striking pattern of gene expression inspired myriad evolutionary theories, the most successful of which identify scenarios that create an asymmetry between the maternally and paternally inherited gene copies that favors silencing of one of the copies. Most notably, imprinting can evolve when gene dosage affects kin interactions (typically involving conflict) or when silencing enhances coadaptation by coordinating traits expressed by interacting kin. Although we have a well‐established theory for the former process (the “Kinship Theory”), the coadaptation process has only been explored for the specific case of interactions between mothers and offspring. Here, we fill this critical gap in our understanding by developing a general “Coadaptation Theory” that explains how imprinting can evolve to coordinate interactions between all types of relatives. Using a simple model in which fitness of an individual is determined by an interaction between its own phenotype (and hence genotype) and that of its social partner(s), we find that when the relatedness of interactants differs through their maternally versus paternally inherited gene copies, then selection favors expression of the allele through which relatedness is higher. The predictions of this Coadaptation Theory potentially apply whenever a gene underlies traits that mediate the outcome of conspecific interactions, regardless of their mechanism or the type of organism, and therefore provide a potential explanation for enigmatic patterns of imprinting, including those underlying adult traits. By providing simple testable predictions that often directly contrast with those derived from alternative theories, our model should play an important role in consolidating our understanding of the evolution of imprinting across genes and species, which will ultimately provide crucial insights into imprinted gene function and dysfunction.

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Section: Resultsmentioning

confidence: 99%

The coadaptation theory for genomic imprinting

O’Brien

Wolf

2017

Evolution Letters

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“…It should be noted that other imprinted genes have diverse functions, notably in energy homeostasis [ 27 , 28 ], or brain function and behaviour [ 29 ]. Some of these functions are difficult to reconcile with the conflict hypothesis, particularly those affecting only post-natal aspects of physiology or behaviour [ 30 ], leading to the proposal of alternatives such as coadaptive evolution [ 31 ], which are not necessarily mutually exclusive with the parental conflict hypothesis [ 32 , 33 ]. Since the discovery of the relationship between Igf2 and Igf2r there have been no other clear examples of imprinted genes with antagonistic growth functions, although oppositely imprinted transcripts at the Gnas locus have antagonistic roles in behaviour and physiology [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Antagonistic roles in fetal development and adult physiology for the oppositely imprinted Grb10 and Dlk1genes

et al. 2014

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BackgroundDespite being a fundamental biological problem the control of body size and proportions during development remains poorly understood, although it is accepted that the insulin-like growth factor (IGF) pathway has a central role in growth regulation, probably in all animals. The involvement of imprinted genes has also attracted much attention, not least because two of the earliest discovered were shown to be oppositely imprinted and antagonistic in their regulation of growth. The Igf2 gene encodes a paternally expressed ligand that promotes growth, while maternally expressed Igf2r encodes a cell surface receptor that restricts growth by sequestering Igf2 and targeting it for lysosomal degradation. There are now over 150 imprinted genes known in mammals, but no other clear examples of antagonistic gene pairs have been identified. The delta-like 1 gene (Dlk1) encodes a putative ligand that promotes fetal growth and in adults restricts adipose deposition. Conversely, Grb10 encodes an intracellular signalling adaptor protein that, when expressed from the maternal allele, acts to restrict fetal growth and is permissive for adipose deposition in adulthood.ResultsHere, using knockout mice, we present genetic and physiological evidence that these two factors exert their opposite effects on growth and physiology through a common signalling pathway. The major effects are on body size (particularly growth during early life), lean:adipose proportions, glucose regulated metabolism and lipid storage in the liver. A biochemical pathway linking the two cell signalling factors remains to be defined.ConclusionsWe propose that Dlk1 and Grb10 define a mammalian growth axis that is separate from the IGF pathway, yet also features an antagonistic imprinted gene pair.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-014-0099-8) contains supplementary material, which is available to authorized users.

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“…We detected switching between maternal and paternal alleles for the imprinted genes Grb10 (Charalambous et al, 2003;Garfield et al, 2011;Cowley et al, 2014;Wilkins, 2014;Ubeda and Gardner, 2015;Wolf et al, 2015) and Igf2 (Gregg et al, 2010a), which are known to switch the alleles in different tissues ( Fig. 6C,D; Table S5).…”

Section: Monoallelically Expressed Transcripts In Poly(a)+ and Total mentioning

confidence: 97%

Monoallelic, antisense and total RNA transcription in an in vitro neural differentiation system based on F1 hybrid mice

Kondo

Kato

Suzuki

et al. 2019

Journal of Cell Science

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We developed an in vitro system to differentiate embryonic stem cells (ESCs) derived from reciprocally crossed F1 hybrid mice into neurons, and used it to investigate poly(A)+ and total RNA transcription at different stages of cell differentiation. By comparing expression profiles of transcripts assembled from 20 RNA sequencing datasets [2 alleles×(2 cell lines×4 time-points+2 mouse brains)], the relative influence of strain, cell and parent specificities to overall expression could be assessed. Divergent expression profiles of ESCs converged tightly at neural progenitor stage. Patterns of temporal variation of monoallelically expressed transcripts and antisense transcripts were quantified. Comparison of sense and antisense transcript pairs within the poly(A)+ sample, within the total RNA sample, and across poly(A)+ and total RNA samples revealed distinct rates of pairs showing anti-correlated expression variation. Unique patterns of sharing of poly(A)+ and poly(A)− transcription were identified in distinct RNA species. Regulation and functionality of monoallelic expression, antisense transcripts and poly(A)− transcription remain elusive. We demonstrated the effectiveness of our approach to capture these transcriptional activities, and provided new resources to elucidate the mammalian developmental transcriptome.

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Genomic Imprinting of Grb10 : Coadaptation or Conflict?

Abstract: Knocking out the Grb10 imprinted gene in a mother compensates for the loss of the same gene in her offspring. Is this evidence of a role for coadaptation in the evolution of imprinting?

Cited by 10 publications

References 35 publications

The coadaptation theory for genomic imprinting

The coadaptation theory for genomic imprinting

Antagonistic roles in fetal development and adult physiology for the oppositely imprinted Grb10 and Dlk1genes

Monoallelic, antisense and total RNA transcription in an in vitro neural differentiation system based on F1 hybrid mice

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