When the Interstate Highway System was first created, AASHTO had a rule that no Interstate and US Route with the same numbers could coexist in a state. Since with both numbering schemes, 50 and 60 would fall in roughly the same part of the country, I-50 and I-60 had to be skipped so they wouldn't share any states with Route 50 and Route 60.
AASHTO has since relaxed that rule, and there are now a few exceptions to it, but it's too late to shoehorn in two major interstates.
AFAIK, the old US Highways were numbered opposite to the Interstate system, at least for round-numbered routes. US-10, 20, 30, etc., more or less proceeded north to south, Interstates are increasing south to north. The middle numbers like 50 would possibly overlap in both systems so designations like I-50 weren't used.
Indeed they are. Route 1 mostly runs along the east cost (key word is "mostly") often next to I-95, and Route 99 used to exist right next to where I-5 is now (it's since been turned into a gaggle of state highways in CA, OR, and WA), while Route 2 runs in the north and Route 90 largely runs next to (or is co-signed with) I-10.
Yup, in fact there are 99W and 99E more or less straddling I-5 and running in generally north-south alignment in the Portland metro area. In recent years I-5 has become increasingly congested, not just in "rush hour". Consequently 99E/W are also heavily used as commuters try to escape traffic. Hard to solve the problems created by our success.
Us highways 50 and 60 exist and the location of Interstate 50 and 60 would be kinda close to where US-50 and 60 are, so they were probably skipped to avoid confusion.
They were skipped for unknown reasons. US Highway 50 and 60 exist though. Could possibly be why. An Interstate 50 and a US 50 in close proximity would be...confusing.
AASHTO has since relaxed that rule, and there are now a few exceptions to it, but it's too late to shoehorn in two major interstates.