Welcome by CARTA Co-Director and Salk Institute President, Jerry Joyce. Opening remarks by Event Co-chair, Johannes Krause.
Ancient DNA: New Revelations
Friday, November 07, 2025Abstracts
Abstracts
The genome sequences of Neandertals and Denisovans have provided a wealth of new information about the origins, migrations, and interactions of ancient humans. These genomes have revealed that mixture between hominin groups was common: all modern humans outside Africa carry around 2% Neandertal DNA from a single major episode of Neandertal gene flow, while the ancestors of present-day Asians and Oceanians also met and mixed with multiple, genetically distinct Denisovan populations.
Archaeological evidence suggests multiple dispersals of modern humans out of Africa, with early fossils identified in East and Southeast Asia over 50 thousand years ago. In contrast, genomic studies indicate that all present-day non-African populations descend primarily from a single dispersal after ~50 ka, though the migration routes of ancestral populations across Eurasia and Oceania remain unclear. I will show how we are using the distribution of Neandertal and Denisovan ancestry in ancient and present-day modern humans to determine when, where and how often modern and archaic humans met and mixed. These findings offer a new perspective on the history of early modern human dispersals.
The sequencing of genomes from archaic humans, such as Neanderthals and Denisovans, has transformed our understanding of human evolutionary history. These ancient genomes reveal that modern humans did not evolve in isolation but interbred with now-extinct groups, leaving lasting genetic legacies. To date, genomic sequences from 31 archaic human individuals, including four sequenced to high coverage, have provided unprecedented insights into the population structure, social organization, and adaptation of this now-extinct lineages, allowing us to reconstruct our own evolutionary history and the mechanisms that led to modern human success. This talk reviews nearly three decades of research on archaic human DNA and what we have learned about how these groups lived, as well as how admixture between different lineages may have contributed both to the extinction of archaic humans and the thriving of modern humans. Ultimately, ancient genomes show that the success of our species was not predetermined but forged through encounters, exchanges, and adaptations, and that the legacies of archaic humans live on in our biology today, continuing to influence what it means to be human.
Changes in gene regulation are key drivers of human evolution. However, how and which regulatory changes shaped human adaptations remains largely unknown. Here, we employed massively parallel reporter assays (MPRAs) in skeletal and neural cells to uncover the function of the 71,443 variants distinguishing Neanderthals and Denisovans from modern humans. This extensive catalog allowed us to discover hundreds of variants that altered human expression, providing the first insight into the function of noncoding variants in recent human evolution. We use these MPRAs to identify evolutionary trends and detect several examples of convergent evolution. For example, both lineages completely silenced an enhancer of KDM8, a gene involved in tumor progression, but Neanderthals and Denisovans achieved this through motif disruption, while modern humans did so through hypermethylation. Finally, we developed a method to reconstruct morphological profiles from DNA sequence and methylation and used it to reconstruct Denisovan anatomy. Using the profile, we scanned the fossil record and identified unclassified specimens matching the Denisovan profile. We found that Harbin and Dali were likely Denisovans, and that Kabwe might have been related to the ancestor of Neanderthals and Denisovans. Overall, our work helps shed light on the key regulatory changes underlying human evolution.
Humans have a deep and complex relationship with microbes. Beyond disease, microbes also profoundly shape human health and behavior through their activity in the microbiome and their diverse roles in food and cuisine. And yet we know very little about the origin, evolution, or ecology of the trillions of microorganisms that call us home. Recent advances in genomic and proteomic technologies are opening up dramatic new opportunities to investigate the complex and diverse microbial communities that have long inhabited our human bodies and our food systems - both in sickness and in health. From infectious disease to the microbiome, microbes are the invisible and often overlooked figures that have profoundly shaped human culture and influenced the course of human history. Focusing on the long arc of human-microbial relationships preserved by ancient DNA over the past 100,000 years, this talk explores how emerging research on pathogen evolution and the recent loss of commensal microbes is changing how we understand human health – both today and in the past.
The Kazakh and Mongolian Steppes span ~5,000 km west to east along the northern latitude of Asia. This unique ecozone allowed rapid movements of people, animals, goods, and ideas across Eurasia since prehistory and harbored numerous polities of pastoralists that made tremendous impacts on human history. However, the region’s dynamic genetic history has been emerging only recently from archaeogenomic studies. Here, I will overview our current understanding of the region’s genetic history leveraging on our recent studies. Specifically, I will portrait 1) the pre-pastoralist hunter-gatherer population structure, 2) the dispersal of the Afanasievo herders and their genetic legacy, 3) a contrasting genetic impact of the Middle-Late Bronze Age Andronovo herders in the Kazakh and Mongolian Steppes, 4) distinct Iron Age transformations in the Kazakh and Mongolian Steppes, and 5) genetic information to understand the formation and social structure of steppe empires. Together with this overview, I will highlight 1) the divergent genetic history of the Kazakh and Mongolian Steppe populations, 2) the genetic interaction between the steppe pastoralists and their neighbors, and 3) a comparison between the genetic history of human and domesticated animal populations. The emerging genetic view illuminates the poorly recorded history of the Kazakh and Mongolian Steppes and provides an interconnected perspective on the history of Eurasia.
Ancient DNA offers insights into prehistoric events that are invisible through archaeology or modern genetics alone. Over the past decade, archaeogenetics has analyzed more than 15,000 ancient genomes spanning 45,000 years of western Eurasian prehistory, uncovering dozens of migrations that reshaped Europe.
This lecture will trace the earliest, unsuccessful attempts of modern humans to settle Europe after leaving Africa around 50,000 years ago, when they also interbred with Neandertals. We will then examine two major genetic turnovers of the Neolithic: first, the spread of early farmers from Anatolia about 8,000 years ago, who brought agriculture and domesticated animals, and later mixed with indigenous hunter-gatherers; and second, the arrival of mobile herders from the Pontic steppe around 5,000 years ago, who introduced pastoralism and possibly Indo-European languages.
We will conclude with migrations triggered by the collapse of the Roman Empire, showing how they further shaped Europe’s genetic landscape. Modern Europeans thus represent mixtures of multiple ancestral groups, reflecting that large-scale mobility has been the norm throughout history.
Ancient DNA has revolutionized the study of the human past, providing unprecedented insights into ancient migrations and interactions among populations. Central Asia, due to its geographic location between Europe and Asia, has seen experienced diverse human and hominin migrations, which have been a focus of genetic, archaeological, linguistic, and historical research. Recent advances in population genetics have revealed the complex ancestry of Central Asian groups, both modern and ancient. Significant progress has also been made in understanding the role of natural selection in shaping genetic variation across the region. In this talk, I will present recent developments in our knowledge of Central Asia’s genetic history, integrating findings from both modern and ancient genomic studies. Additionally, I will highlight the selective pressures that have influenced the genomes of Central Asians through time, shedding light on the dynamic interplay between admixture, adaptation, and cultural change.
The human genetic history of South Asia has been shaped by its pivotal location at the crossroads of East and West Eurasia, dramatic landscapes such as the Himalayas, and longstanding socio-cultural practices like endogamy. A consequence is the diversity of East and West Eurasian genetic ancestral lineages found in South Asians today. Increasing genome-wide data from ancient and present-day humans are providing emerging insights into the demographic processes that underlie present-day genetic diversity of South Asians and how they interface with evidence from archaeology, anthropology, linguistics, and oral histories. Human history in South Asia is also closely intertwined with the animals that humans domesticated, traded, and moved with them, offering yet another window into the dynamics of human mobility and connectivity in the past. This talk will focus on ancient and modern DNA insights into the origins of present-day human genetic diversity in South Asia, evolutionary history of domesticates, and broader implications for our understanding of human movements and interactions across Eurasia.
Genetic data is transforming the understanding of our own species and refining historical chapters at different scales around the globe. However, despite the globalization of biotechnologies to analyze the human genome, indigenous populations from the Americas and Oceania remain underrepresented in large-scale genomic studies. In this talk, I will discuss recent efforts to characterize the genetic profile of Indigenous Americans throughout the analysis of ancient and modern DNA, as well as their relationship within and beyond the continent, including the possibility of prehistoric contacts with Pacific Islanders. This topic poses challenges and opportunities to adequately study human diversity not only for the benefit of genetic research and science, but also for the benefit of the local communities, which are bearers of a unique evolutionary history that has been recorded in their DNA. This rapidly evolving field also raises questions about the best practices when studying the DNA of underrepresented ancestries while conducting cutting-edge science in a more equitable way.
Question and answer session with all speakers. Wrap-Up by symposium co-chair, Christina Warinner. Closing remarks by CARTA Executive Co-Director, Pascal Gagneux.
