Danny Cipriani has been overlooked by Eddie Jones once again after being left out of England's squad for the autumn international series.
Cipriani has made a strong start to the season at Gloucester and was named Gallagher Premiership player of month for September, yet is missing from the 36-man group named for the Tests against South Africa, New Zealand, Japan and Australia.
Owen Farrell and George Ford are present as the recognised fly-halves, although Henry Slade and Alex Lozowski provide cover in the position.
For the first time in Jones' reign, Dylan Hartley must share the leadership duties with Farrell after the pair were named co-captains.
Ben Morgan has been picked for the first time since the 2015 World Cup as a result of the crisis at number eight that has seen Billy Vunipola and Sam Simmonds ruled out of the entire series by injury and Nathan Hughes miss all but the final match due to suspension.
Wing Chris Ashton is present despite having yet to make his debut for Sale with his seven-week ban for a tip-tackle elapsing this weekend.
Manu Tuilagi has overcome a succession of injuries to win inclusion and he will be competing with Ben Te'o - who has not played this season because of thigh and ankle problems - for selection in midfield.
England's loosehead prop resources have been decimated by Mako Vunipola's absence due to a calf issue and the international retirement of Joe Marler, leaving Alex Hepburn and Ben Moon as the only recognised options in the position.
The squad contains eight uncapped players and confirms the decline of veterans Dan Cole and James Haskell, who have been omitted once more.
Jones' outlook on a punishing series that opens against the Springboks at Twickenham on November 3 remains positive despite missing 18 players to injury, suspension and retirement.
Jones said: "I'm really happy with the squad. We can only control what we can control and injuries have happened."
Forwards (20) - Tom Curry (Sale Sharks), Charlie Ewels (Bath Rugby), Jamie George (Saracens), Dylan Hartley (co-captain, Northampton Saints), Alec Hepburn (Exeter Chiefs), Ted Hill (Worcester Warriors), Maro Itoje (Saracens), George Kruis (Saracens), Courtney Lawes (Northampton Saints), Zach Mercer (Bath Rugby), Ben Moon (Exeter Chiefs), Ben Morgan (Gloucester Rugby), Michael Rhodes (Saracens), Nick Schonert (Worcester Warriors), Brad Shields (Wasps), Kyle Sinckler (Harlequins) Elliott Stooke (Bath Rugby), Sam Underhill (Bath Rugby), Harry Williams (Exeter Chiefs), Mark Wilson (Newcastle Falcons).
Backs (16) - Chris Ashton (Sale Sharks), Mike Brown (Harlequins), Danny Care (Harlequins), Joe Cokanasiga (Bath Rugby), Elliot Daly (Wasps), Nathan Earle (Harlequins), Owen Farrell (co-captain, Saracens), George Ford (Leicester Tigers), Alex Lozowski (Saracens), Jonny May (Leicester Tigers), Jack Nowell (Exeter Chiefs), Henry Slade (Exeter Chiefs), Ben Te'o (Worcester Warriors), Manu Tuilagi (Leicester Tigers), Richard Wigglesworth (Saracens), Ben Youngs (Leicester Tigers).