<description>David Gokhman of the Weizmann Institute of Science explores how changes in gene regulation shaped recent human evolution. His team used massively parallel reporter assays in skeletal and neural cells to test 71,443 genetic variants that distinguish Neanderthals and Denisovans from modern humans, building a catalog that reveals hundreds of noncoding variants that alter gene expression. The work uncovers evolutionary trends and examples of convergent evolution, including an enhancer of KDM8, a gene involved in tumor progression, that was completely silenced in both archaic and modern human lineages through different mechanisms: motif disruption in Neanderthals and Denisovans, and hypermethylation in modern humans. Gokhman also introduces a way to reconstruct anatomical profiles from DNA sequence and methylation, using it to model Denisovan anatomy and scan the fossil record. The results suggest that the Harbin and Dali fossils were likely Denisovans, while Kabwe may have been related to the ancestor of Neanderthals and Denisovans, helping to clarify the regulatory changes underlying human evolution. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 41195]</description>

CARTA: Ancient DNA - New Revelations

David Gokhman of the Weizmann Institute of Science explores how changes in gene regulation shaped recent human evolution. His team used massively parallel reporter assays in skeletal and neural cells to test 71,443 genetic variants that distinguish Neanderthals and Denisovans from modern humans, building a catalog that reveals hundreds of noncoding variants that alter gene expression. The work uncovers evolutionary trends and examples of convergent evolution, including an enhancer of KDM8, a gene involved in tumor progression, that was completely silenced in both archaic and modern human lineages through different mechanisms: motif disruption in Neanderthals and Denisovans, and hypermethylation in modern humans. Gokhman also introduces a way to reconstruct anatomical profiles from DNA sequence and methylation, using it to model Denisovan anatomy and scan the fossil record. The results suggest that the Harbin and Dali fossils were likely Denisovans, while Kabwe may have been related to the ancestor of Neanderthals and Denisovans, helping to clarify the regulatory changes underlying human evolution. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 41195]

CARTA: Evolutionary Switches - How Regulatory Variants Shaped Human Evolution with David Gokhman

<description>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. Diyendo Massilani of Yale University School of Medicine 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.   Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 41193]</description>

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. Diyendo Massilani of Yale University School of Medicine 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.   Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 41193]

CARTA: Archaic Human Genomes with Diyendo Massilani

<description>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. Janet Kelso, professor at Max Planck Institute for Evolutionary Anthropology, shows how using the distribution of Neandertal and Denisovan ancestry in ancient and present-day modern humans can determine when, where and how often modern and archaic humans met and mixed. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 41192]</description>

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. Janet Kelso, professor at Max Planck Institute for Evolutionary Anthropology, shows how using the distribution of Neandertal and Denisovan ancestry in ancient and present-day modern humans can determine when, where and how often modern and archaic humans met and mixed. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 41192]

CARTA: Archaic Introgression Reveals Human Dispersals with Janet Kelso

<description>The human body has traits that evolved at different times, from 1.5 billion to 2 million years ago, each bringing health benefits and risks. Multicellularity enabled organs and cancer. The immune system defends us but can cause inflammation. Breastfeeding supports infant health but relates to breast cancer risk. Menstruation and invasive placentas improved reproduction but led to pain and cancer risks. Human-specific traits like bipedalism and aging brought new issues like back pain and childbirth problems. Hair loss and sweat glands helped us stay cool but increased skin cancer risk. Our hunter-gatherer past shaped our microbiome and health, but also made us prone to modern diseases from lifestyle changes. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Humanities] [Science] [Show ID: 40702]</description>

CARTA - Mismatch: Human Origins & Modern Disease

The human body has traits that evolved at different times, from 1.5 billion to 2 million years ago, each bringing health benefits and risks. Multicellularity enabled organs and cancer. The immune system defends us but can cause inflammation. Breastfeeding supports infant health but relates to breast cancer risk. Menstruation and invasive placentas improved reproduction but led to pain and cancer risks. Human-specific traits like bipedalism and aging brought new issues like back pain and childbirth problems. Hair loss and sweat glands helped us stay cool but increased skin cancer risk. Our hunter-gatherer past shaped our microbiome and health, but also made us prone to modern diseases from lifestyle changes. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Humanities] [Science] [Show ID: 40702]

CARTA: Mismatch: Human Origins and Modern Disease - Questions Answers and Closing Remarks

<description>Humans have long been exposed to three main types of smoke: from early domestic fires, modern wildfires, and more recently, tobacco and fossil fuel pollution. All release tiny particles from partly burned plants, containing harmful chemicals like nitrogen oxides and carcinogens. These particles raise risks for lung cancer, dementia, and even childhood obesity. Studies show that air pollution can disrupt brain chemistry, increase Alzheimer’s-related proteins, and activate stress-related genes (NFkB, Nrf2). A new drug (GSM-15606) shows promise in reducing brain damage from pollution in mice. People with the ApoE4 gene may be more vulnerable, while the ApoE3 gene, possibly evolved 200,000 years ago, may offer some protection. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Humanities] [Science] [Show ID: 40700]</description>

Humans have long been exposed to three main types of smoke: from early domestic fires, modern wildfires, and more recently, tobacco and fossil fuel pollution. All release tiny particles from partly burned plants, containing harmful chemicals like nitrogen oxides and carcinogens. These particles raise risks for lung cancer, dementia, and even childhood obesity. Studies show that air pollution can disrupt brain chemistry, increase Alzheimer’s-related proteins, and activate stress-related genes (NFkB, Nrf2). A new drug (GSM-15606) shows promise in reducing brain damage from pollution in mice. People with the ApoE4 gene may be more vulnerable, while the ApoE3 gene, possibly evolved 200,000 years ago, may offer some protection. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Humanities] [Science] [Show ID: 40700]

CARTA: Three Smokes in the Evolution of the Human Exposome with Caleb Finch

Multidisciplinary researchers explore the origins of humanity and the many facets of what makes us human.

CARTA - Anthropogeny (Video)

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