I presume by "they", you mean AMCAS. You enter all of the courses you ever took (as well as the grade) and assign it to a certain category (biology, chemistry, history, etc). You will also have to have your transcripts sent from all of your college experiences. AMCAS will use these transcripts to verify what you entered. From the grades you entered, AMCAS will calculate a GPA that considers all of your college coursework. All natural science courses are factored into your sGPA, regardless of whether or not they are prereqs.
The AMCAS instruction booklet (google it) has more detailed information if you desire.
-admissions committee interviewer / senior medical student