According to the fitness of heterozygote was lower than homozygote among panmictic population,the process of generational accumulate of mutant gene r was considered.Branch point of r's frequency by generational evolution which revealed the hereditary incompatibility between R and r,was worked out,and it was found that genetic drift can make r have higher frequency to surpass the branch point to form reproductive isolation.It was not enough to have the three conditions of mutation,genetic drift and natural selection to be the drive of biological evolution;hybrid weakness,the repelling interaction between the genetic background of original population and the new mutation,were also needed.