Winger Sibusiso Nkosi scored two tries as South Africa rallied from an early 24-3 deficit to defeat England in Johannesburg.
Nick Isiekwe was Eddie Jones' "project player" on tour last year, but now he is ready to start for England in Joe Launchbury's absence.
Brad Shields will be one of two England debutants against South Africa, while injury keeps Joe Launchbury out.
It is all change for South Africa, as Rassie Erasmus has selected a new XV for Saturday's game against England.
The Springboks have been dealt a blow for their Test series with England, as Bismarck du Plessis and Frans Steyn will not feature.
England's tour of South Africa is something Ben Youngs is able to put into perspective after his sister-in-law's fight against cancer.
Despite being questioned over his methods, Eddie Jones is adamant England's players train "appropriately" for Test rugby.
South Africa were beaten in bizarre circumstances by Wales on Saturday, with new coach Rassie Erasmus acknowledging the need to improve.
There was a late twist in the tale as Rassie Erasmus suffered defeat to Wales in his first match as South Africa coach.
Wales coach Warren Gatland has named Ellis Jenkins as captain for his side's clash with South Africa on Saturday.
Seven uncapped players will be given the chance to impress Rassie Erasmus when South Africa face Wales in Washington on Saturday.
Eddie Jones has been forced to bring in three replacements for the upcoming series against the Springboks.
Eddie Jones is confident England will have "opportunities" to create history in South Africa.
History will be made when Stormers flanker Siya Kolisi leads the Springboks in three home Tests against England in June.
A mammoth 43-man squad has been selected for matches against Wales and England by Springboks chief Rassie Erasmus.
Saracens finished their Premiership final win over Exeter Chiefs without Owen Farrell, but his injury was not serious.