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| 1537 |
| | With the end of the siege of Cuzco, and the flight of Manco Inca, the Spanish have full control of Peru | |
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| 1542 |
| | New Laws are passed in Spain, in an attempt to protect the Indians on the encomiendas of Spanish America | |
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| 1545 |
| | Rich seams of silver are discovered at Potosi, in modern Bolivia | |
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| 1548 |
| | La Paz is founded on the trade route between Lima and the newly discovered silver mines at Potosi | |
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| 1549 |
| | Brazil becomes a Portuguese royal province, under the control of a governor general | |
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| 1549 |
| | The first Portuguese governor general of Brazil selects Bahia (now Salvador) as his capital | |
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| c. 1550 |
| | Africans, bought in the Portuguese trading posts of west Africa, are shipped across the Atlantic as slaves | |
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| c. 1550 |
| | Spanish galleons assemble each year at Portobelo to deliver European goods and to ship home the metals of Latin America | |
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| c. 1570 |
| | Privateers frequent the Spanish main to plunder the richly laden caravels on their way home to Europe | |
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| 1579 |
| | Francis Drake seizes a Spanish vessel laden with gold and silver in the Pacific, formerly a safe area for Spain | |
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