Captain Owen Farrell and hooker Jamie George have withdrawn from England's squad to face South Africa due to injury.
Farrell sustained an ankle problem during Saturday's 32-15 win over Australia, while fellow Saracens player George suffered a knee issue in that game.
Jack Singleton and his uncapped Gloucester team-mate Harry Elrington have been called up by head coach Eddie Jones ahead of next Saturday's Twickenham clash with the Springboks.
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The Rugby Football Union also announced Joe Marler would join the group on Friday after completing his 10-day isolation period following a positive coronavirus test result.
England are preparing to meet South Africa for the first time since suffering a 32-12 defeat in the final of the 2019 World Cup in Yokohama.
Head coach Jones has named a 34-man squad for the game, which rounds off his side's autumn campaign following consecutive wins over Tonga and the Wallabies.
Front-rower Singleton, 25, returns to the international fold having won three caps in 2019, including a substitute appearance against the United States during the World Cup pool stage.
Loosehead prop Elrington, 27, joined Gloucester ahead of the current season having begun his career with London Irish.