David Haig and the Evolutionary Epigenetics of Imprinted Genes: Methylation, IGF Pathways, and Parental Conflict

By SWA

Introduction

In the complex choreography of genetics and evolution, one of the most intriguing discoveries has been that not all genes follow the basic rule of biparental expression. A special class of genes—imprinted genes—are expressed in a parent-of-origin-specific manner. Central to our understanding of why this happens is the work of David Haig, an evolutionary biologist whose “parental conflict hypothesis” has reshaped how scientists view fetal growth, gene regulation, and evolutionary strategy.

This article explores Haig’s theory and how methylated imprinted genes, particularly those in the insulin-like growth factor (IGF) pathway, govern critical processes like growth and metabolism.

Genomic Imprinting: One Parent, One Voice

Genomic imprinting refers to a form of gene expression where only one allele of a gene is expressed, depending on whether it comes from the mother or the father. The other allele is epigenetically silenced, most commonly via DNA methylation, where methyl groups are added to DNA to repress transcription.

This selective gene silencing plays a crucial role in developmental processes such as growth regulation, nutrient allocation, and brain function.

 Imprinted genes defy the usual "two working copies" rule. Instead, they come with built-in silencing depending on parental origin.

Haig’s “Parental Conflict Hypothesis”

David Haig, a professor at Harvard University, proposed the parental conflict theory of imprinting in the early 1990s (Haig & Westoby, 1989). His core idea is evolutionary:

  • Paternal genes tend to promote fetal growth, seeking to maximize the current offspring's survival—even at a cost to the mother.

  • Maternal genes are more conservative, limiting resource use to protect the mother's well-being and future reproductive potential.

Thus, imprinted genes evolved as a genetic battleground—a reflection of conflicting parental interests over maternal investment.

Methylated Imprinted Genes in the IGF Pathway

Nowhere is this parental tug-of-war more evident than in the insulin-like growth factor (IGF) pathway, a crucial regulator of fetal and postnatal growth.

IGF2: The Growth-Promoter

  • Expressed only from the paternal allele

  • Promotes fetal growth by stimulating cell proliferation and nutrient uptake

IGF2R: The Growth-Controller

  • Expressed only from the maternal allele

  • Binds to IGF2 and leads it to degradation, thereby reducing growth signals

Role of Methylation

  • DNA methylation marks are added during the formation of egg or sperm cells.

  • These marks silence one allele—for example, methylation silences the maternal copy of IGF2, allowing only the paternal copy to be active.

  • For IGF2R, it’s the opposite: the paternal copy is methylated and silenced, so only the maternal copy is expressed.

This regulatory system acts as a molecular compromise between parental strategies:

“Dad’s gene says: Grow more!
Mom’s gene says: Not so fast!”

Consequences of Imprinting Imbalance

When the imprinting process goes wrong—due to mutations, methylation errors, or deletions—it can cause serious developmental disorders:

References


© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

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