For a first gun, I always recommend the revolver. It is a fool proof weapon and easy to maintain. A good choice of calibers is always the .38/.357. You can shoot low recoil .38 special ammo which is fairly cheap and abundant. For the protection side, you can always load up the .357. I have found for females, never allow them to shoot something with a lot of recoil, It will not be a pleasant experience, and they will not want to shoot any longer. By all means, always use more than adequate ear protection and also always use eye protection. There are many ranges where you can go and try out different weapons before you decide on which one to buy.
My wife shoots a S&W 22, and carries an S&W 22 mag. In my opinion, it is a little light, but she is very comfortable with it. As always, you need to keep up the practice for both accuracy and comfort.
If your wife has never shot a handgun, I would definitely start her off with a rimfire (.22). They are very cheap to shoot, and you get to practice a whole lot for little money.