Terrible title, sorry.
So Mako computes a value for install_requires in setup.py. This results in the wheel thats built being python version specific - concretely if you build a wheel using Python 3.2 it won't depend on MarkupSafe, but on 3.2 or 2.6/2.7 it will will.
This shows up when wheels are reused across Python versions (one way to do this is via the pip wheel cache): https://github.com/pypa/pip/issues/3025 - if Python 3.2 is used to install mako, then when an install is done on 3.3 MarkupSafe isn't installed. Conversely if Python 3.3 is used to do the first install, then on 3.2 MarkupSafe will be installed even though its (presumably) incompatible.
A similar issue applies to the argparse conditional: if the wheel is built on 2.6, it will drag in argparse when installed on 2.7/3.x.
Your setup.cfg has universal=1 so it looks like you intend to build wheels suitable for multiple Python versions, but to do so you cannot use computed requirements - you must instead use conditional requirements.
Attached is a patch to do this.
Unfortunately, sufficiently old versions of pip and setuptools don't support computed requirements. I don't know the minimum versions that do, but pip 1.5.6 (the default on my Trusty install) does - the following is from a wheel built with the patch attached.:
$ pip install ./Mako-1.0.1-py2.py3-none-any.whl Unpacking ./Mako-1.0.1-py2.py3-none-any.whl Downloading/unpacking MarkupSafe>=0.9.2 (from Mako==1.0.1) Downloading MarkupSafe-0.23.tar.gz Running setup.py (path:/home/robertc/.virtualenvs/t/build/MarkupSafe/setup.py) egg_info for package MarkupSafe Installing collected packages: Mako, MarkupSafe Running setup.py install for MarkupSafe building 'markupsafe._speedups' extension x86_64-linux-gnu-gcc -pthread -DNDEBUG -g -fwrapv -O2 -Wall -Wstrict-prototypes -fno-strict-aliasing -D_FORTIFY_SOURCE=2 -g -fstack-protector-strong -Wformat -Werror=format-security -fPIC -I/usr/include/python2.7 -c markupsafe/_speedups.c -o build/temp.linux-x86_64-2.7/markupsafe/_speedups.o x86_64-linux-gnu-gcc -pthread -shared -Wl,-O1 -Wl,-Bsymbolic-functions -Wl,-Bsymbolic-functions -Wl,-z,relro -fno-strict-aliasing -DNDEBUG -g -fwrapv -O2 -Wall -Wstrict-prototypes -D_FORTIFY_SOURCE=2 -g -fstack-protector-strong -Wformat -Werror=format-security -Wl,-Bsymbolic-functions -Wl,-z,relro -D_FORTIFY_SOURCE=2 -g -fstack-protector-strong -Wformat -Werror=format-security build/temp.linux-x86_64-2.7/markupsafe/_speedups.o -o build/lib.linux-x86_64-2.7/markupsafe/_speedups.so Successfully installed Mako MarkupSafe Cleaning up...