The ultimate source of all variation from which natural selection can operate is genetic mutations. Numerous cellular genetic repair systems exist to ensure that mutational expression is extremely rare. These repair systems pose major problems for evolution because virtually all genetic innovations caused by base pair changes will be corrected (and thus not expressed), or the cell itself will be destroyed. If genetic repair systems were perfect, then all macroevolution clearly would be impossible. These genetic repair systems argue against macroevolution, at least as caused by the accumulation of mutations.