Geographic isolation. Some members of a species get isolated from the main group and proceed to develop their own particular genome. Isolating factors: an impassable canyon such as what the Grand Canyon has done to certain species of ground squirrels, trapped on an island such as the DoDo was, travel so far away that the extreme range of the species effectively isolates one side from the other.
Sexual preference. Extreme factiousness on the selection of a mate by some physical attribute or behavioral trait will determine the isolation of a group. This is most pronouncedly displayed in the birds.
Divergent modes of livelihood. If a certain physical trait becomes important to a species manner of survival then keeping that trait emphasized in the gene pool is vitally important. Only those specialists that intermarry will survive in this mode of living.
