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The reason for the existence of most of the world's cities is obvious to the student of geography. New York and Shanghai control deep ports and straddle great rivers bringing trade from the interior; Paris and London are at the crossing points of major cross-country rivers; Johannesburg sits atop a great mountain of gold ore; and Moscow and Madrid are at the heart of their great nations, easily able to control even the more distant corners of the land. Mecca, however, is different, as the city exists solely because it is holy. Even centuries before the birth of the Prophet Muhammad, the leaders of Mecca established that their city was the pre-eminent holy site in western Arabia and established a truce for pilgrims to the city. In the process, one effect of this was that Mecca became a center for might today be described as tourism, as even ancient visitors needed places for food, water, and sleep. At the same time, they could make offerings in the temples and leave with mementos of their time in Mecca. Many also found it convenient to bring their trade goods to the markets of Mecca, where they could find visitors bringing interesting wares from across the region, and the city also enjoyed the status of a trade center.
Of course, Mecca is now best known for being Islam's holiest city, revered as the birthplace of Muhammad and the site where Allah first revealed the Qu'ran to him. Within Mecca is the Ka'aba, a building housed within the Al-Masjid al-Haram (Great Mosque) that is considered the holiest site, and wherever they are in the world, Muslims face in the direction of the Ka'aba while praying. A pilgrimage to Mecca is considered a necessity for devout Muslims at some point in their lives, and the city itself is off limits to non-Muslims. Indeed, Mecca is so integral to Islam that the name of the city has entered the English lexicon and is a commonplace reference to any area closely associated with something (such as Paris often being called the mecca of fashion).
Even centuries before the birth of the Prophet Muhammad, Jews settled in the area that became Medina to escape persecution at the hands of the Babylonians and Romans, meaning the area and its arid environment brought inhabitants precisely because it wasn't an attractive or resource rich area. In fact, the city fated to become the second holiest city in Islam earned that spot simply by straddling trade routes to the religious city of Mecca, which brought traders and pilgrims in large enough numbers to make it a trade center.
While people in the West are more familiar with Jerusalem's importance to Jews and Christians, Jerusalem's particular importance to the religion of Islam is without question one of the major sticking points in the Israeli-Palestinian conflict. Prior to Israeli control, Jerusalem had been predominantly controlled by Muslim rulers since the 7th century and had been used as a type of political currency, legitimizing the ruling dynasty's claim over the city. This right of control by Muslims was viewed no more differently than control over Mecca and Medina in the Arabian Peninsula. For the world's Muslim population, Jerusalem is a holy site because Muslims believe the Prophet Muhammad visited Jerusalem where he ascended to heaven during the famous "Night Journey." There was also a period of time during the Prophet's life when Muslims prayed in the direction of Jerusalem, as opposed to Mecca. Just as in Judaism and Christianity, Jerusalem plays a central role in End of Days prophecies in Islamic theology.
As a result, Jerusalem has been an important symbol for Muslims for nearly 1,300 years, and it has played a crucial political role throughout the history of Islamic civilization as this important city has passed from ruler to ruler and dynasty to dynasty.