Genes serve as fundamental blueprints, guiding the development and function of all living organisms. While most genes are expressed from both inherited copies, imprinted genes represent a unique exception. These genes exhibit a distinct characteristic: their activity depends entirely on whether they were inherited from the mother or the father. This unusual mode of inheritance offers intriguing insights into how genetic information is utilized.
What Are Imprinted Genes?
Imprinted genes are a small subset where only one of the two inherited copies is active, or “turned on,” in an individual’s cells. The active copy is determined by its parent of origin; either the maternal or paternal copy is expressed, but not both. For instance, if a gene is paternally imprinted, only the copy inherited from the mother will be active, and vice versa. This differs from typical Mendelian inheritance, where both gene copies usually contribute to traits, and expression is determined by the DNA sequence, not the parental source.
This selective expression means that if the single active copy of an imprinted gene is faulty or missing, there is no backup copy to compensate, unlike non-imprinted genes where the other copy might still function. Approximately 228 imprinted genes are known in humans, often clustered on specific chromosomes, with these clusters containing regulatory elements that control the imprinting process.
The Mechanism of Gene Imprinting
The precise control over which parental gene copy is expressed involves epigenetic modifications, which alter gene activity without changing the underlying DNA sequence. A primary mechanism is DNA methylation, where small chemical tags called methyl groups are added to specific DNA segments. This methylation acts like a “silence” switch, repressing the activity of the gene it is attached to. The repressed allele is methylated, while the active allele remains unmethylated.
Another mechanism involves histone modifications, changes to the proteins around which DNA is wound. These modifications can alter how tightly DNA is packaged, influencing whether genes are accessible for expression. These epigenetic marks, including both DNA methylation and histone modifications, are established or “imprinted” during the formation of sperm and egg cells in the parents, setting the specific parental origin mark before fertilization.
Once established in the germline, these epigenetic marks are maintained throughout development and passed down through successive cell divisions in the offspring. The imprinting process is dynamic, as these marks must be erased and then reset in the germline of each new generation to establish new parent-specific imprints.
Roles of Imprinted Genes in Biology
Imprinted genes play roles in various biological processes, particularly in mammalian development and physiology. Their function includes involvement in embryonic and placental development, influencing nutrient allocation and fetal growth. For example, paternally expressed imprinted genes tend to promote growth, while maternally expressed ones may limit it, reflecting a balance in resource allocation between the parents. This dynamic is sometimes explained by the “parental conflict hypothesis,” suggesting an evolutionary drive for parents to maximize their genetic contribution to offspring.
Beyond early development, imprinted genes contribute to brain development and function, influencing complex behaviors and neural circuitry. They are involved in regulating cognitive function and social behavior. Imprinted genes also participate in metabolic regulation, affecting how the body processes and utilizes energy.
Their unique expression pattern allows for precise control over gene dosage in specific tissues or developmental stages. This fine-tuned regulation benefits complex biological processes that require balanced gene activity. The presence of imprinted genes in therian mammals and flowering plants suggests a shared evolutionary strategy for regulating growth and development.
Imprinted Genes and Human Health
When gene imprinting is disrupted, it can lead to various human health conditions. These disorders often arise because the normally active single copy of an imprinted gene becomes non-functional due to a deletion, mutation, or an error in the imprinting mark itself. Since there is no backup copy from the other parent, the loss of function can have consequences.
Prader-Willi Syndrome and Angelman Syndrome are two examples linked to imprinting defects on chromosome 15. Prader-Willi Syndrome results from the loss of function of specific paternally expressed genes in the 15q11-13 region. Individuals with this syndrome often experience hypotonia (poor muscle tone), feeding difficulties in infancy, followed by insatiable hunger leading to obesity, and intellectual disabilities.
Conversely, Angelman Syndrome is caused by the loss of function of a maternally expressed gene, UBE3A, located in the same 15q11-13 region. This condition manifests with developmental delays, intellectual disability, speech impairment, seizures, and behavioral traits such as frequent laughter and hand-flapping. Other conditions, like Beckwith-Wiedemann syndrome, are associated with aberrant imprinting on chromosome 11p15.5, leading to overgrowth and a risk of certain childhood cancers. These examples highlight the importance of genomic imprinting for normal development and health.