Mewtwo before receiving Clefairy's DNA
Mewtwo debuted in Bring Down the Strongest Pokémon!!, where it was created by Giovanni and his twin brother to become the ultimate unbeatable Pokémon. Bill and his wife are held hostage by them and they force Bill to continue the creation of Mewtwo using Mew's DNA. During the creation, Mewtwo breaks out of the machine that the brothers created it in. Their plans are foiled however when Red's Clefairy obtains a DNA switching machine and mixed his DNA with Mewtwo's. Clefairy managed to defeat Mewtwo with Mewtwo's DNA. Giovanni released Mewtwo shortly after Mewtwo is defeated.
Clefairy with Mewtwo's DNA
In The Revenge of Mewtwo!!, Mewtwo recreates the DNA switching machine. Mewtwo attempts to switch Clefairy's DNA with a Rattata. However, Red's Pikachu managed to knock Mewtwo into the DNA switching machine and activate it. Hence, Mewtwo received Clefairy's DNA, causing the psychic Pokémon to become as obnoxious and goofy as Clefairy. Mewtwo managed to become popular as a gag Pokémon, and even managed to write a gag book (Mewtwo's Gag Series) and had a gag movie coming up soon.
Blue eventually captured Mewtwo prior to The Pokémon Banana League, where it was sent out during a League match against Red. Mewtwo still has Clefairy's DNA, and tried to use gag moves against Clefairy. However, Clefairy's body gag eventually defeated Mewtwo unintentionally.