Biology subjects

Witonsky, D.

Publications and source records attributed to Witonsky, D..

4 recordsLinked to original sources

bioRxiv2026

Ancient human genomes from Ladakh reveal Tibetan, South Asian, and Central Asian admixture over the last three millennia

The trans-Himalayan region of Ladakh occupies a strategic position at the crossroads of South Asia, the Tibetan Plateau, and Central Asia, with archaeological evidence pointing to long-term cultural exchanges across these regions. However, the human genetic history of Ladakh remains largely unexplored. We generated paleogenomic data from seven individuals recovered from two sites in Western Ladakh - the Old Lady Spider Cave and Hanu - of which six are dated to 531-585 CE and one to the 19th century CE. The older individuals share substantial genetic ancestry with Tibetan groups but also harbor major contributions from two additional sources: one corresponding to the currently-oldest observation of the Ancestral North Indian genetic component that characterizes several present-day populations in North India and Pakistan, and another related to ancient Central Asian groups, with admixture events occurring between [~]2,100-2,500 years ago. In contrast, the later individual falls within a previously described ancient northern Himalayan genetic cline based on [~]1,100-1,300-year-old individuals from Himachal Pradesh, with ancestries related to ancient Tibetan and Steppe-related sources. Stable isotope analysis suggests that these individuals were local to Ladakh in late life and practiced an agro-pastoralist subsistence. Our study establishes that Ladakhs central role in Eurasian economic and socio-cultural networks was shaped by dynamic and sustained gene flow linking high-altitude Himalayan groups with both lowland South Asia and Inner Asia.

genetics↗

bioRxiv2025

Genomic profiling of active vitamin D colonic responses in African- and European-Americans identifies an ancestry-related regulatory variant of POLB

We measured genomic responses to active vitamin D, 1,25-dihydroxyvitamin D (1,25D), in colonic organoids from individuals of African and European ancestry. Given protective effects of 1,25D for gastrointestinal conditions such as colorectal cancer, organoid cultures enabled evaluation of condition-specific responses in relevant target tissue. We found significant alterations in transcriptional and chromatin accessibility responses to 1,25D treatment, including some with ancestry-associated differences, and also elucidated the role of cis-genetic variance on treatment responses. Integration of genomic profiling with genetic mapping found an insertion-deletion variant that explains ancestry-associated differences in 1,25D regulation of POLB, an oxidative DNA repair enzyme involved in colorectal carcinogenesis, which also showed signals of positive natural selection. These findings highlight the importance of including diverse individuals in functional genomics studies to identify potential drivers of population-level differences relevant for clinical outcomes, and to uncover functional mechanisms that may be obscured by ancestry variation.

genomics↗

bioRxiv2022

Integrating genetic and oral histories of Southwest Indian populations

Over the past decade, genomic data has contributed to several insights on global human population histories. These studies have been met both with interest and critically, particularly by populations with oral histories that are records of their past and often reference their origins. While several studies have reported concordance between oral and genetic histories, there is potential for tension that may stem from genetic histories being prioritized or used to confirm community-based knowledge and ethnography, especially if they differ. To investigate the interplay between oral and genetic histories, we focused on the southwestern region of India and analyzed whole-genome sequence data from 158 individuals identifying as Bunt, Kodava, Nair, and Kapla. We supplemented limited anthropological records on these populations with oral history accounts from community members and historical literature, focusing on references to non-local origins such as the ancient Scythians in the case of Bunt, Kodava, and Nair, members of Alexander the Greats army for the Kodava, and an African-related source for Kapla. We found these populations to be genetically most similar to other Indian populations, with the Kapla more similar to South Indian tribal populations that maximize a genetic ancestry related to Andaman Islanders. We did not find evidence of additional genetic sources in the study populations than those known to have contributed to many other present-day South Asian populations. Our results demonstrate that oral and genetic histories may not always provide consistent accounts of population origins and motivate further community-engaged, multi-disciplinary investigations of non-local origin stories in these communities.

genetics↗

bioRxiv2018

The genetic prehistory of the Andean highlands 7,000 Years BP though European contact

The peopling of the Andean highlands above 2500m in elevation was a complex process that included cultural, biological and genetic adaptations. Here we present a time series of ancient whole genomes from the Andes of Peru, dating back to 7,000 calendar years before present (BP), and compare them to 64 new genome-wide genetic variation datasets from both high and lowland populations. We infer three significant features: a split between low and high elevation populations that occurred between 9200-8200 BP; a population collapse after European contact that is significantly more severe in South American lowlanders than in highland populations; and evidence for positive selection at genetic loci related to starch digestion and plausibly pathogen resistance after European contact. Importantly, we do not find selective sweep signals related to known components of the human hypoxia response, which may suggest more complex modes of genetic adaptation to high altitude.\n\nOne Sentence SummaryAncient DNA from the Andes reveals a complex picture of human adaptation from early settlement to the colonial period.

genomics↗