The greatest genetic diversity in East Asians is found in Southeast Asia (Chapter 1.22), and for this reason it is thought that East Asia was first colonised from the south around 50,000 years ago, not long after the exodus from Africa.

Within East Asia, one of the most prominent genetic-geographic features is the north–south difference already noted in classical blood group markers as summarised by Cavalli-Sforza, Menozzi and Piazza (1994) and reproduced in mtDNA data by Forster et al. (2001). The discontinuity is at approximately 45° N latitude, which was also the permafrost boundary during the Last Glacial Maximum twenty thousand years ago. Mitochondrial demographic expansion dates north of this latitude are younger than twenty thousand years, and dates south of this more ancient. This suggests that humans were restricted to southern refuges during the last Ice Age Maximum, and then recolonised the wastelands when the climate improved.

Similar to areas within the northern latitudes, the Tibetan plateau would have represented a significant climatic and environmental challenge to early human settlement. Successful colonisation here requires not only adaptation to the cold, but also adaptation to the hypoxic conditions at more than 3000 metres above sea level. Tibetans today have in fact adapted to the low oxygen levels by virtue of a point mutation in the EPAS1 gene (Yi et al. 2010; Beall et al. 2010). This point mutation influences the production of red blood cells and therefore of haemoglobin in their blood. The polymorphism conferring this advantage shows a 78% frequency difference between Tibetans and Han Chinese, representing one of the fastest human genetic changes to date, assuming Han Chinese and Tibetans separated genetically fairly recently, during the Holocene.