Mitogenome evidence shows two radiation events and dispersals of matrilineal ancestry from northern coastal China to the Americas and Japan.

Although it is widely recognized that the ancestors of Native Americans (NAs) primarily came from Siberia, the link between mitochondrial DNA (mtDNA) lineage D4h3a (typical of NAs) and D4h3b (found so far only in East China and Thailand) raises the possibility that the ancestral sources for early NAs were more variegated than hypothesized. Here, we analyze 216 contemporary (including 106 newly sequenced) D4h mitogenomes and 39 previously reported ancient D4h data. The results reveal two radiation events of D4h in northern coastal China, one during the Last Glacial Maximum and the other within the last deglaciation, which facilitated the dispersals of D4h sub-branches to different areas including the Americas and the Japanese archipelago. The coastal distributions of the NA (D4h3a) and Japanese lineages (D4h1a and D4h2), in combination with the Paleolithic archaeological similarities among Northern China, the Americas, and Japan, lend support to the coastal dispersal scenario of early NAs.

ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity.

Adaptation to reduced energy production during aging is a fundamental issue for maintaining healthspan or prolonging life span. Currently, however, the underlying mechanism in long-lived people remains poorly understood. Here, we analyzed transcriptomes of 185 long-lived individuals (LLIs) and 86 spouses of their children from two independent Chinese longevity cohorts and found that the ribosome pathway was significantly down-regulated in LLIs. We found that the down-regulation is likely controlled by ETS1 (ETS proto-oncogene 1), a transcription factor down-regulated in LLIs and positively coexpressed with most ribosomal protein genes (RPGs). Functional assays showed that ETS1 can bind to RPG promoters, while ETS1 knockdown reduces RPG expression and alleviates cellular senescence in human dermal fibroblast (HDF) and embryonic lung fibroblast (IMR-90) cells. As protein synthesis/turnover in ribosomes is an energy-intensive cellular process, the decline in ribosomal biogenesis governed by ETS1 in certain female LLIs may serve as an alternative mechanism to achieve energy-saving and healthy aging.

Complete mitogenomes document substantial genetic contribution from the Eurasian Steppe into northern Pakistani Indo-Iranian speakers.

To elucidate whether Bronze Age population dispersals from the Eurasian Steppe to South Asia contributed to the gene pool of Indo-Iranian-speaking groups, we analyzed 19,568 mitochondrial DNA (mtDNA) sequences from northern Pakistani and surrounding populations, including 213 newly generated mitochondrial genomes (mitogenomes) from Iranian and Dardic groups, both speakers from the ancient Indo-Iranian branch in northern Pakistan. Our results showed that 23% of mtDNA lineages with west Eurasian origin arose in situ in northern Pakistan since ~5000 years ago (kya), a time depth very close to the documented Indo-European dispersals into South Asia during the Bronze Age. Together with ancient mitogenomes from western Eurasia since the Neolithic, we identified five haplogroups (~8.4% of maternal gene pool) with roots in the Steppe region and subbranches arising (age ~5-2 kya old) in northern Pakistan as genetic legacies of Indo-Iranian speakers. Some of these haplogroups, such as W3a1b that have been found in the ancient samples from the late Bronze Age to the Iron Age period individuals of Swat Valley northern Pakistan, even have sub-lineages (age ~4 kya old) in the southern subcontinent, consistent with the southward spread of Indo-Iranian languages. By showing that substantial genetic components of Indo-Iranian speakers in northern Pakistan can be traced to Bronze Age in the Steppe region, our study suggests a demographic link with the spread of Indo-Iranian languages, and further highlights the corridor role of northern Pakistan in the southward dispersal of Indo-Iranian-speaking groups.

Neolithic millet farmers contributed to the permanent settlement of the Tibetan Plateau by adopting barley agriculture.

The permanent human settlement of the Tibetan Plateau (TP) has been suggested to have been facilitated by the introduction of barley agriculture ∼3.6 kilo-years ago (ka). However, how barley agriculture spread onto the TP remains unknown. Given that the lower altitudes in the northeastern TP were occupied by millet cultivators from 5.2 ka, who also adopted barley farming ∼4 ka, it is highly possible that it was millet farmers who brought barley agriculture onto the TP ∼3.6 ka. To test this hypothesis, we analyzed mitochondrial DNA (mtDNA) from 8277 Tibetans and 58 514 individuals from surrounding populations, including 682 newly sequenced whole mitogenomes. Multiple lines of evidence, together with radiocarbon dating of cereal remains at different elevations, supports the scenario that two haplogroups (M9a1a1c1b1a and A11a1a), which are common in contemporary Tibetans (20.9%) and were probably even more common (40-50%) in early Tibetans prior to historical immigrations to the TP, represent the genetic legacy of the Neolithic millet farmers. Both haplogroups originated in northern China between 10.0-6.0 ka and differentiated in the ancestors of modern Tibetans ∼5.2-4.0 ka, matching the dispersal history of millet farming. By showing that substantial genetic components in contemporary Tibetans can trace their ancestry back to the Neolithic millet farmers, our study reveals that millet farmers adopted and brought barley agriculture to the TP ∼3.6-3.3 ka, and made an important contribution to the Tibetan gene pool.