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Flanker Justin Tipuric will captain Wales as head coach Warren Gatland creates 13 adjustments because of their final World Cup pool match against Uruguay.
Wing Josh Adams and centre Hadleigh Parkes are the only players remaining from Wednesdays triumph over Fiji.
After recovering from appendix operation lock Adam Beard makes his first World Cup look.
Quarter-final qualification has been already achieved by wales and require two points to finish top of Pool D.
Wales were planning to create changes with the fixture, provided the turnaround out of Wednesday success against Fiji.
The need was compounded by the number of accidents picked up during that match.
Gatland said George North carried an knock in the Fiji game along with the need to break contributed to Adams again starting despite the latter suffering a dead leg at that match.
Adams switches from the wing Hallam Amos making his first tournament appearance at 11.
Hooker Ryan Elias, lock Bradley Davies and scrum-half Aled Davies additionally earn their first taste of action in Japan.
Injuries and rotation mean Wales have chosen Tomos Williams and scrum-halves Gareth Davies because their only backs alongside six forwards.
That means there is not going to be a professional fly-half cover Rhys Patchell, that starts at Biggars lack at 10.
Gatland has suggested the cover will come from Parkes, with Amos, who hasnt played in his mature career 10, or experience of playing rugby at fly-half.
The replacement scrum-halves could also be requested to cover the place.
The Wales coach says having four days involving the Fiji and Uruguay games has enforceda tiny juggling act and selection talks included asking flanker James Davies to play at the backs.
We knew that right from the beginning we were going to expose some gamers, said Gatland.
I spoke before the World Cup [to say] we would probably enter this game with only one 10 anyway so were looking for cover there too.
Its been hard with the short turnaround, however weve got a forward pack that are all fresh and pretty excited and theyre looking forward to the opportunity.
The message to the players for the game against Uruguay is that the door is not closed. There are chances for players to venture out there and impress and stake a claim for those quarter-finals.
Gatland added:We spoke about whether we could have put James Davies in the backs. He has a lot of sevens experience and Justin (Tipuric) is also pretty comfortable playing the wider channels too.
Were convinced weve cover with players and being able to move around if we will need to do that.
We have had two players straight back up in Hadleigh Parkes and Josh Adams.
Ideally wed have liked to have given Josh a rest, but has not been the case and that is why weve ended up going for a 6-2 split with 2 nines covering the springs.
Gareth (Davies) went on the wing at the conclusion of the Fiji match and did a good job to us. We now have two grade nines who will cover different positions.
Wales: Halfpenny; Adams, Watkin, Parkes, Amos; Patchell, A Davies; Smith, Elias, Lewis, B Davies, Beard, Shingler, Tipuric (capt), Wainwright.
Replacements: Dee, Carre Ball James Davies G Davies.
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