There is genetic evidence for two major historical lineages in New Guinea and neighboring islands: a first wave from the Malay Archipelago perhaps 50,000 years ago when New Guinea and Australia were a single landmass called Sahul and, much later, a wave of Austronesian people from the north who introduced Austronesian languages and pigs about 3,500 years ago.

Papuan ethnic groups / tribes in the Indonesian province of West Papua include Arfak, Borai, Doreri, Hatam, Irarutu, Koiwai, Kuri, Madewana, Mairasi, Maniwak, Mbaham, Matta, Meiah, Miere, Meyah, Moire, Moru, Moskona, Napiti, Oburauw, Roon, Roswar, Sebyar, Sougb, Soviar, Sumuri, Wamesa, Warumba, Waruri, Wondama.

[8] Papuan ethnic groups / tribes in the Indonesian province of Southwest Papua include Abun, Ambel, Batanta, Biak (Betew, Kafdaron, Bikar, Usba, Wardo), Biga, Butlih, Domu, Fiawat, Imekko (Inanwatan-Bira, Matemani-Iwaro, Kais-Awe, Kokoda-Emeyode), Irires, Ma'ya (Kawe, Langanyan, Wawiyai), Matbat, Maybrat (Ayamaru, Mare, Karon Dori, Ayfat, Aytinyo), Meyah, Moi-Ma'ya, Moi, Mpur, Nerigo, Tehit, Tepin, Yahadian, Yaben-Konda.

[11][12][13] It is estimated that people reached Sahul (the geological continent consisting of Australia and New Guinea) between 50,000 and 37,000 years ago.

The genetic makeup of Papuans is primarily derived from Ancient East Eurasians, which relates them to other mainland Asian groups such as the "AASI", Andamanese, as well as East/Southeast Asians, although Papuans may have also received some gene flow from an earlier group (xOoA), around 2%,[17] next to additional archaic Denisovan admixture in the Sahul region.

[12][13][11]There is evidence that the ancestors of Papuans and related groups "underwent a strong bottleneck before the settlement of the region, and separated around 20,000–40,000 years ago".

[20] Denisovan introgressions may have influenced the immune system of present-day Papuans and potentially favoured "variants to immune-related phenotypes" and "adaptation to the local environment".