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An undetermined time ago, the Guardian of the Milky Way, Lanancuras, started to harbor a desire for power, and eventually invaded the worlds he was assigned to protect. Being bound to the galaxy, he was able to absorb parts of a planet and add it to his strength. In his footsteps was a following from many planets, creatures that had pledged allegiance and were now named Kadrians. By the time the other Celestial Guardians confronted him, he was too strong to be defeated. The Celestial Guardians all gave up a part of their power and combined it into a single Guardian, Mushra, whose core was used to create a card to seal Lanancuras. The prison was made from parts of the planets that had suffered under his power and with the help of the card, the meteorite was able to restrain him, as planets are beings on their own and hold a significant amount of power as well.
The meteorite was sent off into the galaxy to be sealed forever. Meanwhile, the way Lanancuras had increased his strength had consequences on the planets of the Milky Way. On Earth, it was in the shape of a virus that merged with human DNA and destroyed the human that way. In order to eliminate the virus, scientists worked on combining human DNA with the DNA of animals and other creatures immune to the effects. They succeeded and created a sentient race known as Enterrans, Engineered Earthlings. Eventually, a cure was found, and the human race survived. This all took place around the 22nd century.
The Kadrians meanwhile worked on getting their master free, and they found the perfect place. The Guardians noticed too late that the meteorite was being redirected and heading towards Earth. The Guardians held a vow that they would not interfere with the way the planets reacted as this was up to the inhabitants and nature, so he was out of their influence. At impact, the seal holding Lanancuras in ripped due to the impact, leaving only the planetary pieces to hold the Kadrian king in.
At impact, Lanancuras sent out three special gems that he had corrupted from the meteorite and placed them into the strongest Enterran he could find: Mushrambo. However, he also felt the Guardians influence and how they secured the energy they had given to Mushra, away from the meteorite. Lanancuras guessed that they would at some time grant this power to someone to counter him, and it could not be an Enterran since in a way, the Enterrans were a product of him becoming evil, and easily to be influenced because they were card-based creatures. It had to be a human. He chose six more generals to lead the Enterrans into a war against the humans, making them believe humans enslaved them.
Mushrambo led the war, and was like all the others completely oblivious to the reason he felt such a hatred. All they knew was that they wanted the humans destroyed, and only Rusephine and Mushrambo knew that the meteorite had something to do with the whole thing.
At one point, the Guardians elected a keeper of their power. The baby girl Yakumo Tatsuro was chosen, daughter of Daigo Tatsuro who had helped develop the Enterrans and the cure. Daigo knew they were losing the war, and under the inspiration of the Celestial Guardians he built a place where he could make Yakumo survive, knowing she was special. The Guardians sent Hakuba, a Celestial Equine who would transform into the Reversian Blade upon death. The most powerful weapon in the universe was shaped like a robot to transport Yakumo and was always aware of his task.
Around the age of 4, Daigo had finished building an underground for Yakumo to survive in, which would allow her to live for 30 years and only grow a single year in physical shape (50 in the dubbed version). Just at the moment this happened, Mushrambo destroyed the last sanctuary of the humans, the place called Shinzo. Then he went after Yakumo, and killed Daigo in the process. However, the machines keeping Yakumo alive activated and awoke her powers. Yakumo froze the energy of Mushrambo and ripped him apart with her own aura. Mushrambo died, and his EnCard was divided into three gems. The Guardians guided these gems away for a later purpose (Mushra, Saago and Kutal were later send to the past, but unable to make a difference).
The machine malfunctioned, though this was in fact the Guardians doing. Yakumo slept for 300 years (500 in the dubbed version) and woke up at the age of 17 close to the time Lanancuras would break out. She was told to search for Shinzo, the last sanctuary of the human race and bring peace to the Enterrans. In fact, this journey was to help her become aware of her powers.
A while before that, the three gems had been given to three Enterrans. One of them was Mushra, who had been given a new body on Enterra by the Guardians, since they were both card based beings. Mushra received the Crown of Koira, a powerful artifact that had been given to him before to seal Lanancuras, but that was then used by Lanancuras to control Mushrambo.
He met Yakumo after being hung above a waterfall as punishment for a crime. She freed him, and he somehow felt compelled to go with her (the gem at work). Later they met Saago, who held the blue gem, and Kutal, who held the green gem.
Yakumo's powers took long to develop, as she was a peaceful person and willing to forgive. She often had a conflict with Mushra and his violent nature.
The story tells about the group travelling and the enemies they meet, and bit by bit parts of the past are revealed. At the end of the first season, the timeline was altered by the destruction of the Evil Mushrambo, leaving only Yakumo and the three gems. The battle resulted in the timeline being altered. As a result, the human race didn't die out and the war between humans and Enterrans never happened.
This also meant that in the second timeline Lanancuras never used up a lot of energy to control the war, and while he was completely dormant in the first timeline, he was about to break free in the second.