The Ohio River, which streams westward from Pittsburgh, Pennsylvania, to Cairo, Illinois, is the largest tributary, by volume, of the Mississippi River in the United States. At the confluence, the Ohio is considerably bigger than the Mississippi and, thus, is hydrologically the main stream of the whole river system, including the Allegheny River further upstream. The river had great significance in the history of the Native Americans, as numerous civilizations formed along its valley. For thousands of years, Native Americans used the river as a major transportation and trading route. Its waters connected communities. In the five centuries before European conquest, the Mississippian culture built numerous regional chiefdoms and major earthwork mounds in the Ohio Valley, such as Angel Mounds near Evansville, Indiana, as well as in the Mississippi Valley and the Southeast. The Osage, Omaha, Ponca and Kaw lived in the Ohio Valley, but under pressure from the Iroquois to the northeast, migrated west of the Mississippi River to Missouri, Arkansas and Oklahoma in the 17th century. The Ohio River is a climatic transition area, as its water runs along the periphery of the humid subtropical and humid continental climate areas. It is inhabited by fauna and flora of both climates. In winter, it regularly freezes over at Pittsburgh but rarely further south toward Cincinnati and Louisville. At Paducah, Kentucky, in the south, near the Ohio's confluence with the Mississippi, it is ice-free year-round. Paducah was founded there because it is the northernmost ice-free reach of the Ohio.