With Manu Tuilagi ruled out of the Twickenham encounter and Jonathan Joseph released to London Irish, Twelvetrees and Brad Barritt are the only specialist centres in Stuart Lancaster's squad.
Owen Farrell and Toby Flood also provide midfield options for the Calcutta Cup clash.
Ben Foden is another high profile omission from the squad, with David Strettle preferred, and Mike Brown and Alex Goode the full-backs.
Foden missed the autumn internationals due to an ankle injury but has been in fine form for Northampton Saints and was tipped for an international recall.
"We've had to make some tough calls with a lot of competition for places," said Lancaster.
"The players' attitude and application in training has been first rate and we know those going back to their clubs and playing in the Anglo-Welsh Cup will be pushing hard for contention for the Ireland match."
Meanwhile backs coach Andy Farrell has dismissed Jim Telfer's comments. The Lions legend has been reported as laballing England as "too arrogant, too pretentious and too condescending."
"I definitely don't recognise anything he has said," said Farrell.
"He's Scottish isn't he, very passionate about his country and he wants to give his lads as much belief as he can.
"He cares about his country. It is him trying to do the right thing by his own country, to try and motivate them.
"People say this every year about the English anyway. It has stuck now. That is why we take it tongue-in-cheek. We know exactly what we are about."
Forwards: Dan Cole (Leicester Tigers), Dylan Hartley (Northampton Saints), James Haskell (London Wasps), Joe Launchbury (London Wasps), Courtney Lawes (Northampton Saints), Joe Marler (Harlequins), Ben Morgan (Gloucester Rugby), Geoff Parling (Leicester Tigers), Chris Robshaw (Harlequins), Mako Vunipola (Saracens), David Wilson (Bath Rugby), Tom Wood (Northampton Saints), Tom Youngs (Leicester Tigers)
Backs: Chris Ashton (Saracens), Brad Barritt (Saracens), Mike Brown (Harlequins), Danny Care (Harlequins), Owen Farrell (Saracens), Toby Flood (Leicester Tigers), Alex Goode (Saracens), David Strettle (Saracens), Billy Twelvetrees (Gloucester Rugby), Ben Youngs (Leicester Tigers)
Released players: Mouritz Botha (Saracens), Lee Dickson (Northampton Saints), Ben Foden (Northampton Saints), Jonathan Joseph (London Irish), Matt Kvesic (Worcester Warriors), Ugo Monye (Harlequins), Henry Thomas (Sale Sharks), Billy Vunipola (London Wasps), Thomas Waldrom (Leicester Tigers)