Julian R. Homburger

Patagonia represents the final frontier of the human out-of-Africa expansion, where humans have lived for at least 13,500 years, yet the genetic adaptations of its indigenous populations remain understudied. We analyzed genome-wide data from 71 present-day individuals across 7 Patagonian locations. Our analyses reveal widespread European admixture initiating approximately 10 to 12 generations ago, followed by region-specific demographic trajectories. We identified a profound north-south genetic differentiation. Populations from the Chiloé Archipelago and Argentinean Patagonia share ancestry with the Mapuche, whereas individuals from Tierra del Fuego exhibit a unique, deeply rooted genetic component shared with ancient Fueguian groups. To identify prehistoric local adaptations, we performed selection scans on masked Native American genomic segments. We detected robust selection signals predating European contact in genes associated with height and skeletal development (SUPT3H, CADM1, RUNX2), lipid metabolism (MSMO1, LYPLA1, SORT1/PSCR1/CELSR2), and energy homeostasis (ZNF202). Furthermore, we observed a significant enrichment of Native American ancestry within the Major Histocompatibility Complex on chromosome 6. In conclusion, our findings indicate that the current admixed populations in Patagonia exhibit signals of local adaptation that likely originated in their ancient indigenous ancestors. These groups accumulated critical morphological, metabolic, and immunological adaptations to their extreme environment and local pathogens, traits that remained highly beneficial even after European admixture.

Patagonia, the last region settled by humans after the out-of-Africa migration, provides a unique case for studying genetic adaptations to extreme environments. Despite archaeological evidence of human occupation for at least 13,500 years, the genetic history of Indigenous Patagonians remains understudied. Here, we analyze genome-wide data from individuals with high Native American ancestry to investigate their genetic structure, admixture history, and response to environmental pressures through selection. Our results reveal widespread European admixture, which in Chilean Patagonia started 5 generations earlier than in the capital of the colony, suggesting prolonged European contact relative to lower latitudes. We identified a strong north-south genomic differentiation, where common ancestry with Mapuche people is observed in northern Patagonia while Tierra del Fuego shows a unique component of genetic variation. We found selection signals predating European contact, possibly shaped during the settlement of native ancestors in Patagonia. These signals support adaptation to extreme cold and maritime diet, including genomic regions associated with height ( SUPT3H, CADM1, RUNX2 ), lipid metabolism ( MSMO1, SORT1/PSCR2, CELSR2 ), and energy homeostasis ( ZNF202 ). Furthermore, enrichment of Native American ancestry was observed in the MHC complex, likely representing the genetic footprint of past selection events driven by adaptation to endemic pathogens that were still beneficial after admixture with Europeans. These findings provide novel insights into the genetic legacy of Patagonian populations, demonstrating how natural selection has shaped their resilience to environmental challenges and the dynamics of demographic changes over time.

Significance: As the COVID-19 pandemic drags on, we need strategies for reopening those schools that have remained closed. We developed stochastic network models to study the risks associated with returning to in-person learning during the COVID-19 pandemic, and to explore the value of mitigation measures in reducing these risks. Our models indicate that the risk of school outbreaks increases as community prevalence increases, and that secondary schools pose greater control challenges than primary schools. The models reveal that a number of measures can help substantially: dividing students into multiple cohorts who attend school on an alternating basis, frequently testing teachers and students, and vaccinating teachers and staff. Basic transmission control strategies such as mask use, social distancing, and ventilation remain essential.

During the initial stages of the COVID-19 pandemic, many workplaces and universities implemented institution-wide proactive testing programs of all individuals, ir-respective of symptoms. These measures have proven effective in mitigating outbreaks. As a greater fraction of the population becomes vaccinated, we need to understand what continued benefit, if any, proactive testing can contribute. Here, we address this problem with two distinct modeling approaches: a simple analytical model and a more simulation using the SEIRS+ platform. Both models indicate that proactive testing remains useful until a threshold level of vaccination is reached. This threshold depends on the transmissibility of the virus and the scope of other control measures in place. If a community is able to reach the threshold level of vaccination, testing can cease. Otherwise, continued testing will be an important component of disease control. Because it is usually difficult or impossible to precisely estimate key parameters such as the basic reproduction number for a specific workplace or other setting, our results are more useful for understanding general trends than for making precise quantitative predictions.