Tatiana Maslany portrays the core clones including streetwise Sarah, suburban Alison, and lesbian scientist Cosima, whose romance with Delphine begins in episode 6. Creator Graeme Manson stated the clone premise evolved into a feminist statement on body autonomy and reproductive rights, with the show committed to portraying these ethical issues in complexity.

Felix Dawkins, Sarah's gay foster brother, features prominently alongside themes of nature versus nurture and critiques of corporate/scientific control over the clones' bodies and identities. LGBTQ elements appear organically through Cosima without dominating the thriller plot, though they contribute to the series' exploration of diverse clone lives.

Reception highlights Maslany's performances and strong female ensemble, with limited early backlash focused more on later seasons' additions like the trans clone Tony. The progressive framing of autonomy and queer characters influences subplots and character arcs but remains secondary to the central mystery of clone origins and survival.