And reading the file as binary. There's a lesson about the overhead of unicode strings here ;) Your first example takes 3.1 seconds, my previous comment takes

And reading the file as binary. There's a lesson about the overhead of unicode strings here ;) Your first example takes 3.1 seconds, my previous comment takes 2.3 seconds, this one takes 1.4 seconds. start = time.perf_counter() with open("orthocoronavirinae.fasta", "rb") as f: total = sum(map(lambda s: 0 if s[0]==65 else s.count(b"G") + s.count(b"C"), f.readlines())) end = time.perf_counter() print(total, " total") print(end-start, " seconds")