"DNA²" is a science fiction manga series set in a future where overpopulation has become a critical issue. To combat this, scientists develop a method to genetically modify individuals to reduce their reproductive instincts. However, this leads to unintended consequences, creating individuals known as "Mega-Playboys" who possess an uncontrollable urge to seduce women. The story centers on Junta Momonari, a high school student with a peculiar condition: he becomes violently ill at the thought of romantic or sexual situations, making it nearly impossible for him to interact with women.

Junta's life takes a dramatic turn when Karin Aoi, a "DNA Operator" from the future, arrives with a mission to neutralize a Mega-Playboy whose actions threaten to destabilize the timeline. Karin reveals that Junta is destined to become this Mega-Playboy, and her task is to alter his DNA to prevent this future. Using a special dart gun, Karin attempts to modify Junta's genetic code, but the process goes awry, causing Junta to sporadically transform into the very Mega-Playboy she is trying to stop. In this altered state, Junta becomes irresistibly charming and confident, attracting women effortlessly, but he has no memory of his actions afterward.

As the story progresses, Junta struggles to control his transformations while navigating his growing feelings for Karin and his childhood friend, Ami Kurimoto. Karin, meanwhile, faces her own internal conflict as she begins to develop emotions for Junta, despite her training as a DNA Operator, which discourages personal attachments. The narrative explores themes of fate, free will, and the consequences of tampering with human nature, as Junta and Karin work together to prevent the catastrophic future that awaits.

The series introduces additional characters who play pivotal roles, including Ryuji Sugashita, a rival Mega-Playboy with his own agenda, and Kotomi, a mysterious girl with a connection to Junta's past. The plot thickens as the true nature of the Mega-Playboy phenomenon is revealed, involving a deeper conspiracy tied to the genetic experiments of the future. The story balances action, romance, and comedic elements, culminating in a resolution that addresses the ethical dilemmas of genetic manipulation and the power of human connection.