Owen Farrell has been retained as England's captain for the Six Nations but there are several high-profile absentees from the 36-strong squad announced by Eddie Jones on Tuesday.
With the in-form Marcus Smith set to start at fly-half for England in their tournament opener away to Scotland on February 5, Farrell could be deployed as a centre rather than a No 10.
The 30-year-old Farrell, a veteran of 100 Tests, has been sidelined from all rugby since suffering an ankle injury during a Test against Australia at Twickenham in November.
But England coach Jones said he remained the "right man" to lead the team.
"Owen is captain because he has the respect of the team, he's a winner and he drives the competitive spirit of the team," he said.
Courtney Lawes stood in as skipper for November's victories over world champions South Africa and Tonga.
But Farrell, who had surgery, has been recalled by Jones and could now look to prove his fitness by playing for Saracens against London Irish on Sunday.
Asked if he would be happy to select Farrell on the back of just one Premiership match for the Calcutta Cup clash at Murrayfield, Jones replied: "We'll just wait and see. He's due to play this week and then he has another training week and then he will be eligible for selection and we will have to see where he's up to."
Uncapped Bath fly-half Orlando Bailey was included in the squad but experienced playmaker George Ford's international exile continues despite an impressive start to the season with Premiership leaders Leicester.
Elliot Daly, Billy and Mako Vunipola and Sam Underhill, who were all, along with Ford, members of the England squad that reached the 2019 World Cup final, also remained out in the cold.
- 'Make me an idiot' -
But Jones said all those omitted could fight their way back into World Cup contention.
"They've all got areas they need to work on in their games to come back into the team and they've got to play at a level where it makes me an idiot if I don't pick them," the veteran Australian coach explained.
At the other end of the experience spectrum, the uncapped Alfie Barbeary, Ollie Chessum, Tommy Freeman, Ollie Hassell-Collins and Luke Northmore have all been included.
"They're in the squad because we feel they can make a contribution to the team," said Jones. "There's no reason why they can't."
England, who finished fifth in last season's Six Nations before improving markedly in November, will meet on Monday for a five-day training camp.
Following an unbeaten Autumn Nations Series campaign, Jones said a "new" England had moved on from the 2021 Six Nations.
REFRESHED: Wilson eager to impress
NEW HOME: Waratahs to be based at Leichhardt
RETURN HOME: Fiji lock in Suva game
Last year Scotland beat England 11-6 to register their first win over their arch-rivals at Twickenham for 38 years.
"They've got a number of good players in their team who are operating close to their best in (Finn) Russell and particularly (Stuart) Hogg, (Hamish) Watson and (Jamie) Ritchie in the back row," said Jones.
"We know it will be a very, very tough game but we're looking forward to taking it to them."
England squad for Six Nations
Backs: Mark Atkinson (Gloucester), Orlando Bailey (Bath), Owen Farrell (Saracens, capt), Tommy Freeman (Northampton), George Furbank, Ollie Hassell-Collins (London Irish), Max Malins (Saracens), Joe Marchant (Harlequins), Jonny May (Gloucester), Luke Northmore (Harlequins), Jack Nowell (Exeter), Raffi Quirke (Sale), Harry Randall (Bristol), Henry Slade (Exeter), Marcus Smith (Harlequins), Freddie Steward (Leicester), Ben Youngs (Leicester)
Forwards: Alfie Barbeary (Wasps), Jamie Blamire (Newcastle), Ollie Chessum (Leicester), Luke Cowan-Dickie (Exeter), Tom Curry (Sale), Alex Dombrandt (Harlequins), Charlie Ewels (Bath), Ellis Genge (Leicester), Jamie George (Saracens), Joe Heyes (Leicester), Jonny Hill (Exeter), Maro Itoje (Saracens), Courtney Lawes (Northampton), Lewis Ludlam (Northampton), Joe Marler (Harlequins), Bevan Rodd (Sale), Sam Simmonds (Exeter), Kyle Sinckler (Bristol), Will Stuart (Bath)