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Metagenes are a unique genetic component that create superhuman capabilities in certain individuals. It is a product of evolution and genetic tampering by an ancient race of immortals called Celestials. Around .00005% of the global population of humans has such genetic markers.

Metagenes often lie dormant, sometimes for an entire lifetime. The source for the Celestial DNA code is encoded in the amygdala and is triggered as a result of significant stress. It is a 'lifesaver' of sorts for the subject, rapidly rebuilding the genome with new DNA to protect the host. Extreme stresses can include injury, radiation, poisoning, toxic materials, or even birth.

A specific variant of the metagene has been identified as the X-gene. Unlike the emergency encoding contained in the brain, the X-gene carries normally on the back of the cellular chromosomes and is detectable with a chromosomal profiler or cellular scans. X-genes are still activated by the amygdala, specifically triggered at the onset of puberty due to the rising levels of cortisol. It is possible but rare for the X-gene to manifest earlier in life, save instances where the patient was exposed to intense stress for that deliberate purpose.

Certain metahumans are designated as unique sub-species. Homo Superior refers to mutants with chromosomal X-genes. Homo Magi refers to descendants of Atlantis who have natural affinities for magic. Homo Eternis refers to the Eternals, early hominids subjected to rapidly accelerated evolution and directly coded with Celestial DNA. Inhumans are largely descended from an ancient Siberian tribe that was exposed to Terrigen Mists.

Most metahuman talents are barely detectable, manifesting as heightened metabolism and motor skills, or increased intelligence and low level empathic/telepathic talents. Metahuman talents are rarely diverse and tend to fit a few common categorizations. Metahumans are also prone to exaggerated development of secondary physical characteristics, such as grossly deformed skeletal and muscular development. The most common metahuman abilities tend to be lumped into rough groups: 'bruisers' with increased physical characteristics; 'movers' with telekinetic capabilities; 'psychics' capable of telepathic or empathic communication; 'witches' capable of channeling magic; and 'blasters' who can channel energy biologically.

The most substantial research into metagenes was conducted by Nathaniel Essex. His research carried on through World War II under the pseudonym of Josef Mengele. Following the war, Essex disguised himself yet again and helped create the Weapon X program to advance study of metahumans. Logan Howlett became one of the first 'codes' to be deciphered, which is why accelerated healing is a common trait among Weapon X survivors/products.