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  • Review Article
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What good is genomic imprinting: the function of parent-specific gene expression

Key Points

  • Genomic imprinting describes a form of non-Mendelian gene expression, in which the expression of an allele depends on its parent of origin. In most cases, one allele (either the one inherited from mother or the one inherited from father) is expressed and the other is transcriptionally inactive, although more complex patterns are also observed.

  • So far, more than 60 imprinted genes have been identified in mice. In most cases, these genes are also imprinted in humans.

  • Among the vertebrates, imprinting seems to be restricted to the marsupials and the placental mammals.

  • Many imprinted genes influence fetal growth, although some affect behavioural phenotypes that persist into adulthood.

  • The most commonly accepted explanation for the prevalence of diploidy is that it shields the individual from the effects of recessive deleterious mutations. Monoallelic expression exposes these mutations to selection, resulting in a 'cost of imprinting'. Therefore, there must be selective forces that overcome these costs at imprinted loci.

  • This review discusses three theories that attempt to explain the selective advantage of genomic imprinting: 'evolvability' models propose that imprinting enhances the adaptive evolution of a species in the face of a changing environment; the ovarian timebomb hypothesis proposes that imprinting protects female mammals from the ravages of trophoblastic disease; and the kinship theory proposes that imprinting arises as a result of an evolutionary conflict in organisms between genes of maternal and paternal origin.

  • Although the kinship theory has been the most successful theory in explaining the observed patterns of imprinting, it is still unclear whether it can account for all instances of imprinting. This determination will have to await a more detailed understanding of the phenotypic effects of imprinted genes.

Abstract

Parent-specific gene expression (genomic imprinting) is an evolutionary puzzle because it forgoes an important advantage of diploidy — protection against the effects of deleterious recessive mutations. Three hypotheses claim to have found a countervailing selective advantage of parent-specific expression. Imprinting is proposed to have evolved because it enhances evolvability in a changing environment, protects females against the ravages of invasive trophoblast, or because natural selection acts differently on genes of maternal and paternal origin in interactions among kin. The last hypothesis has received the most extensive theoretical development and seems the best supported by the properties of known imprinted genes. However, the hypothesis is yet to provide a compelling explanation for many examples of imprinting.

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Acknowledgements

The authors thank C. Muirhead, R. Trivers and the anonymous reviewers for helpful comments on the manuscript.

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Correspondence to Jon F. Wilkins.

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DATABASES

LocusLink

IGF1R

Igf2

IGF2

IGF-II

Igf2r

IGF2R

Mest

Peg3

OMIM

ovarian teratomas

testicular germ-cell tumours

FURTHER INFORMATION

Harwell imprinting web site

Glossary

EPIGENETIC

Modifications of chromatin or DNA (for example, histone deacetylation and cytosine methylation) that can be stably transmitted through many cell divisions, but can also be reset (unlike the DNA sequence).

EVOLVABILITY

The capacity of a genetic system to generate new adaptations.

FUNCTION

The phenotypic effects of a DNA sequence that are responsible for the selective maintenance of its integrity in the face of mutational processes.

UNIPARENTAL DISOMIES

Both copies of a chromosome derived from one parent.

TERATOMA

A tumour consisting of several cell types.

TROPHOBLAST

The extraembryonic cell population at the maternal–fetal interface. In mice and humans, elements of the trophoblast invade the maternal tissues of the uterus.

CHORIOVITELLINE

A placenta that is derived from the fusion of the extraembryonic yolk sac and the chorion.

KIN

Individuals that share some of their genes by recent common descent.

DEMAND INHIBITOR

A factor that is produced by an offspring reducing the 'demand' on its mother. That is, the production of the factor decreases the individual fitness of the offspring at a benefit to the expected fitness of its mother from other offspring.

DEMAND ENHANCER

A factor that is produced by an offspring increasing the 'demand' on its mother. That is, the production of the factor increases the individual fitness of the offspring at a cost to the expected fitness of its mother from other offspring.

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Wilkins, J., Haig, D. What good is genomic imprinting: the function of parent-specific gene expression. Nat Rev Genet 4, 359–368 (2003). https://doi.org/10.1038/nrg1062

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