A big shake-up is coming to the “Call of Duty” series – arguably gaming’s most popular franchise – after an apparent falling-out between publisher Activision and the two heads of Infinity Ward, developer of last year’s “Call of Duty: Modern Warfare 2” and 2007’s “Call of Duty 4: Modern Warfare.”

As the week has progressed, it’s become clear that Jason West (president) and Vince Zempella (CEO and co-founder) have left the studio, which was bought by Activision in 2003. What, exactly, has been going on is anyone’s guess. In an annual filing with the Securities and Exchange Commission on Monday, Activision said it was “concluding an internal human resources inquiry into breaches of contract and insubordination by two senior employees at Infinity Ward,” warning that “this matter is expected to involve the departure of key personnel and litigation.”

Gossip percolating around the Web, reported by Kotaku.com, suggests there were forces within Infinity Ward who either wanted to make something besides “Call of Duty” games or make a “Call of Duty” title set in the future. Unspecified people at Infinity Ward have also been reported to be unhappy with the fact that Treyarch, another Activision studio, is allowed to make games with “Call of Duty” branding, such as “Call of Duty: World at War” and “Call of Duty 3,” sometimes using technology Infinity Ward created.

But will most gamers even notice the shake-up? While it’s common knowledge among people who follow the industry that Infinity Ward is very much the series’ “A” team, the Treyarch ”Call of Duty” games haven’t exactly been collecting dust in bargain bins. To a certain extent, you have to assume the same people who went to see the “Transformers” movies despite universally awful reviews will buy anything with “Call of Duty” and a soldier or two on the cover, at least for a while. (It doesn’t hurt that Treyarch’s last game, “Call of Duty: World at War,” was no slouch.)

Unsurprisingly, Activision, which never met a sequel it didn’t like, concurs, saying in its SEC filing that “the Company does not expect this matter to have a material impact.”

For its part, Activision seems to be trying its best to preserve one of its hottest properties. Officials at the company have told the remaining employees at Infinity Ward that the studio remains “central to ‘Call of Duty’s’ future,” according to a memo leaked to G4 TV. And the publisher announced the creation of a new business unit to oversee all “Call of Duty” titles. One of those will be a new, upcoming action-oriented game from Sledgehammer Games, which is run by the folks who oversaw Electronic Arts’ highly rated third-person shooter “Dead Space.”

More immediate, though, is Treyarch’s next “Call of Duty” game, which will presumably be out in November. In keeping with Activision’s every-other-year schedule, Infinity Ward wasn’t due to produce another “CoD” title until November 2011. That should give Activision and the leftover Infinity Ward folks plenty of time to sort out where the headless studio fits into the publisher’s plans, as well as give West and Zempella ample opportunity to form a new studio and recruit some of their former underlings.

Stay tuned. This divorce story’s long from over.