Aligning Sequences to Compare Apples to Apples

Before you can compare sequences, you need to make sure that you are comparing stretches of DNA that are evolutionarily related—i.e., that they are homologous sequences.
Two sequences need to be aligned, so that related parts of sequences are lined up against each other and compared.

Crossed out image of an apple and an orange on a balance. — Comparing non-homologous sequences to determine evolutionary relationships among species is like comparing apples to oranges.