Genomic imprinting is a biological process where the expression of a gene is determined by which parent it was inherited from. This phenomenon is an exception to the classical rules of Mendelian inheritance, which involve both parental copies of a gene being active. In the case of imprinted genes, only one copy, either from the mother or the father, is turned on, while the other is silenced.
The concept of genomic imprinting reveals that the maternal and paternal genomes are not functionally identical. For a small subset of our genes, it matters whether the genetic information came from the sperm or the egg. This selective silencing is a programmed event that occurs during the formation of reproductive cells.
This process affects a relatively small number of genes, with around 228 identified in humans, yet they have significant roles in development. These genes are often involved in regulating growth, metabolism, and brain function. The control of their expression is necessary for normal development, and errors in this process can lead to health consequences.
The Parent-of-Origin Effect
The core of genomic imprinting is the parent-of-origin effect, which describes how a gene’s expression depends on its parental source. For most genes, an individual inherits two working copies—one from each parent. For imprinted genes, however, one of these copies is intentionally silenced, meaning only the maternal or paternal allele is active.
This selective gene silencing is a fundamental aspect of development in mammals. The process is gene-specific; for instance, a particular gene might always be silenced if it comes from the mother, while a different gene is silenced only when inherited from the father. This is a predetermined mechanism, not a matter of chance.
Although the number of imprinted genes is small, they are often located together in clusters and are involved in controlling embryonic and placental growth. The parent-of-origin effect ensures that the dosage of these genes is correct. Having two active copies or no active copies of an imprinted gene can disrupt the balance required for normal development, leading to health issues.
The Epigenetic Mechanism of Imprinting
Genomic imprinting is controlled by epigenetics, which are modifications to DNA that regulate gene activity without altering the DNA sequence itself. The primary mechanism is DNA methylation, a biochemical process that attaches small molecules called methyl groups to specific segments of DNA. These methyl groups function like “off” switches, preventing a gene from being expressed.
The process of marking genes as paternal or maternal occurs in the germline—the cells that develop into sperm and eggs. During the formation of these reproductive cells, pre-existing epigenetic marks are erased and then new ones are established according to the individual’s sex. In males, paternal imprints are set in sperm, and in females, maternal imprints are established in eggs.
Once these imprints are established, they are maintained in the somatic cells of the developing embryo and throughout the individual’s life. This maintenance is necessary for the proper regulation of imprinted genes during growth and development. The cycle of erasure and re-establishment of imprints is a continuous process across generations.
Human Syndromes from Imprinting Errors
When the process of genomic imprinting goes awry, it can lead to several recognized medical conditions. Errors can occur through various mechanisms, such as the deletion of a gene, uniparental disomy (inheriting both chromosomes from one parent), or a defect in the imprinting center. These mistakes disrupt parent-specific gene expression, resulting in an incorrect dose of the active gene.
A clear illustration is found in Prader-Willi and Angelman syndromes. Both disorders are linked to the same small region on chromosome 15, which contains several imprinted genes. The specific syndrome that develops depends on which parent’s genetic contribution is lost. Prader-Willi syndrome occurs when the paternal copy of this region is deleted or non-functional, leading to symptoms like weak muscle tone, a constant sense of hunger, and developmental delays.
Conversely, Angelman syndrome arises when the maternal copy of the same region is missing or defective. The loss of the maternally expressed UBE3A gene is a primary cause. This results in a different set of symptoms, including severe intellectual disability, movement disorders, and frequent laughter. Other conditions, like Beckwith-Wiedemann syndrome, are also caused by imprinting errors on chromosome 11 and are associated with overgrowth and an increased risk of childhood cancers.
The Evolutionary Purpose of Imprinting
The leading scientific theory for why genomic imprinting evolved is the parental conflict hypothesis. This hypothesis suggests that imprinting arose from a “tug-of-war” between paternal and maternal genes over the allocation of resources to offspring. From an evolutionary perspective, a father’s reproductive success is enhanced by producing large, strong offspring, so paternal genes tend to favor maximizing fetal growth.
In contrast, a mother’s reproductive interests may be better served by conserving her resources to ensure she can have multiple pregnancies. As a result, maternal genes often act to limit or slow down fetal growth, balancing the needs of the current fetus with the mother’s ability to support future offspring. This genetic conflict results in the differential expression of certain growth-related genes.
A classic example of this dynamic is the insulin-like growth factor 2 (IGF2) gene, a potent growth promoter. The paternal copy of IGF2 is expressed, while the maternal copy is silenced. This aligns with the conflict hypothesis, as it shows a paternal gene pushing for increased growth. This evolutionary tug-of-war over nutrient supply is a driving force behind the development of genomic imprinting in mammals.