This seems entirely reproducible in a local Xenial sbuild using the source packages in https://launchpad.net/~doko/+archive/ubuntu/toolchain/+packages

Interestingly, inspection of the built artifacts in the schroot after all is done yields:

# find . -name copy_reg.py? | xargs ls -l
-rw-rw-r-- 1 barry barry 5597 Nov 30 16:52 ./Lib/copy_reg.pyc
-rw-rw-r-- 1 barry barry 5553 Nov 30 16:53 ./Lib/copy_reg.pyo
-rw-rw-r-- 1 barry barry 5091 Nov 30 17:03 ./debian/tmp-dbg/usr/lib/python2.7/copy_reg.pyc
-rw-rw-r-- 1 barry barry 5047 Nov 30 17:03 ./debian/tmp-dbg/usr/lib/python2.7/copy_reg.pyo
-rw-rw-r-- 1 barry barry 5091 Nov 30 17:02 ./debian/tmp-shdbg/usr/lib/python2.7/copy_reg.pyc
-rw-rw-r-- 1 barry barry 5047 Nov 30 17:02 ./debian/tmp-shdbg/usr/lib/python2.7/copy_reg.pyo

Those are debug builds, so it seems reasonable they are different sizes than the non-debug artifacts in Lib, right?  And since they are self-consistent in size, it seems like it wouldn't be caused by a pyc/pyo write bug.