A new computational approach that can detect ancient hominin ancestry in modern humans without requiring archaic reference genomes reveals a more complex picture of human evolution than previously imagined. Leveraging this approach, researchers report that an unidentified "ghost" population contributed DNA to the ancestors of all modern humans before they dispersed out of Africa. To date, sequencing of Neanderthal and Denisovan genomes has shown that interbreeding between modern humans and archaic hominins shaped present-day genomes. It’s suspected that modern humans also interbred with other, as-yet-unidentified archaic human groups, often called "ghost" populations. Moreover, evidence from living populations and Denisovan genomes points to even older "super-archaic" lineages that split from the human family tree nearly one million years ago or more. However, the scarcity of archaic DNA samples, particularly from older or geographically diverse populations, and the dependence of existing methods on reference genomes have limited the ability to reconstruct the full history of archaic introgression.

 

Here, Yulin Zhang and colleagues developed a new computational method called TRACE that reconstructs ancestral recombination graphs (ARGs) – detailed maps of how genomes have evolved through recombination and shared ancestry – to detect the genetic signatures of ancient interbreeding. Unlike previous approaches, TRACE requires neither an archaic reference genome nor data from an unadmixed outgroup population, allowing scientists to identify previously unknown archaic contributions using only the genomes of living people. The authors validated the approach in simulations and applied it to high-coverage genomes from global human populations, including the 1000 Genomes dataset. TRACE successfully recovered known Neanderthal and Denisovan ancestry while uncovering previously unknown episodes of interbreeding with archaic human groups. The findings suggest that an unidentified "ghost" population contributed DNA to the ancestors of all modern humans before they dispersed out of Africa, rather than only to specific African populations as previously proposed. Surprisingly, this ghost ancestry is also found in genomic regions thought to reject Neanderthal and Denisovan DNA, suggesting those regions may have specifically selected against those lineages rather than against all archaic ancestry. TRACE also found evidence that Oceanians inherited traces of an even more ancient "super-archaic" human lineage indirectly through Denisovans, revealing that the genetic legacy of modern humans was shaped by multiple waves of interbreeding with now-extinct human groups.

 

For reporters interested in research integrity topics, study co-author Priya Moorjani said, “The increasing scale and complexity of genomic datasets make transparency, reproducibility, and open methods more important than ever. Continued efforts to share data, software, and benchmarking frameworks, together with careful validation across independent datasets, will help ensure that new discoveries are both robust and reproducible.”

An analysis of fossil mammals suggests that Mexico served as a long-term evolutionary “holding pen” where North American species adapted and diversified for millions of years before sweeping into South America during the Great American Biotic Interchange 2.8 million years ago. The findings clarify the timing of one of Earth's most consequential migrations and may help explain why North American mammals were more successful migrants than those from South America. The Great American Biotic Interchange (GABI), which reshaped ecosystems after North and South America became connected about 2.8 million years ago, is one of the most important events in the history of life in the Americas. Fossil and genetic evidence shows that the new land bridge allowed waves of animals and plants to move between the continents, with climate change and fluctuating sea levels further influencing these migrations. The exchange was highly uneven – more than half of South America's living mammal genera descend from North American ancestors. In contrast, only a handful of North American mammals trace their origins to South America. While the major migration waves are well established, the timing of mammals’ movement between continents remains poorly understood. Answering that question has been difficult because regions such as Mexico and Central America have had poor fossil records due to preservation and retrieval challenges, leaving a crucial gap in the record of these early migrations.

 

To address these unknowns, Jack Tseng and colleagues collected new fossils of Mexican mammals to reconstruct patterns of mammal dispersal across the Americas through time. Tseng et al. found that Mexico acted as a long-term evolutionary "holding pen," where North American mammals accumulated, adapted, and diversified beginning about 10 million years ago before expanding into South America when the Panamanian land bridge became fully passable around 2.8 million years ago. The findings also revealed little evidence for substantial earlier migrations, supporting the traditional timing of the GABI. Moreover, the authors suggest that the eventual prevalence of North American mammals in South America resulted from a combination of prolonged diversification in Mexico, declining diversity in South America before the interchange, and later extinctions that disproportionately affected South American lineages. “Although the GABI and other past migrations of species were the results of natural processes, studying their dynamics can inform the understanding of modern species invasions facilitated by humans,” write Jenny McGuire and Claire Williams in a related Perspective. “The findings of Tseng et al. suggest that the “winners” of invasions may be those species that can successfully acclimate, such as the North American species that did so in the Mexican holding pen.”

 

For reporters interested in research integrity topics, author Jack Tseng notes, “Sharing of data and analytics codes have been particularly important for analyses such as the ones we present in our work. I would like to see more fossil record databases annotate the degree of vetting that has gone into compilations of data from different sources and the expert opinions that underlie the identifications of specimens to varying levels of specificity.”

About the Study: Is combined inhibition of programmed cell death 1 protein (PD-1) and lymphocyte activation gene 3 (LAG-3) added to standard neoadjuvant chemotherapy (NAC) safe and effective in (formerly HER2)-negative early-stage breast cancer at high risk of recurrence? This phase 2 randomized clinical trial including 78 participants with -negative breast cancer found that combining cemiplimab and fianlimab with paclitaxel-based NAC improved rates of pathologic complete response in all participants, including those with triple-negative and hormone receptor−positive subtypes. Patients positive for the ImPrint immune signature were highly sensitive to the combination, providing a potential biomarker of treatment response. These results indicate that combined PD-1 and LAG-3 inhibition warrants further investigation in -negative breast cancer.

Cells must detect changing levels of oxygen, carbon monoxide, and nitric oxide, but the molecular steps that connect gas sensing to a biological response remain complex.

A new review brings together evidence on heme-based gas sensors and on labile heme, the small and dynamic fraction of heme that can regulate proteins directly.

Across diverse proteins, the same principle emerges: minute changes around heme's iron atom are amplified into larger protein movements that control cellular activity.

The review identifies unresolved steps in this process and highlights time-resolved structural studies and cellular imaging as routes toward synthetic biosensors and therapies targeting heme-mediated pathways.