A Paleogenomic Reconstruction of the Deep Population History of the Andes.

There are many unanswered questions about the population history of the Central and South Central Andes, particularly regarding the impact of large-scale societies, such as the Moche, Wari, Tiwanaku, and Inca. We assembled genome-wide data on 89 individuals dating from ∼9,000-500 years ago (BP), with a particular focus on the period of the rise and fall of state societies. Today's genetic structure began to develop by 5,800 BP, followed by bi-directional gene flow between the North and South Highlands, and between the Highlands and Coast. We detect minimal admixture among neighboring groups between ∼2,000-500 BP, although we do detect cosmopolitanism (people of diverse ancestries living side-by-side) in the heartlands of the Tiwanaku and Inca polities. We also highlight cases of long-range mobility connecting the Andes to Argentina and the Northwest Andes to the Amazon Basin. VIDEO ABSTRACT.

Reconstructing the Deep Population History of Central and South America.

We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions.

When and where to protect forests.

Ongoing deforestation poses a major threat to biodiversity1,2. With limited resources and imminent threats, deciding when as well as where to conserve is a fundamental question. Here we use a dynamic optimization approach to identify an optimal sequence for the conservation of plant species in 458 forested ecoregions globally over the next 50 years. The optimization approach includes species richness in each forested ecoregion, complementarity of species across ecoregions, costs of conservation that rise with cumulative protection in an ecoregion, the existing degree of protection, the rate of deforestation and the potential for reforestation in each ecoregion. The optimal conservation strategy for this formulation initially targets a small number of ecoregions where further deforestation leads to large reductions in species and where the costs of conservation are low. In later years, conservation efforts spread to more ecoregions, and invest in both expanded protection of primary forest and reforestation. The largest gains in species conservation come in Melanesia, South and Southeast Asia, the Anatolian peninsula, northern South America and Central America. The results highlight the potentially large gains in conservation that can be made with carefully targeted investments.

A genetic history of the pre-contact Caribbean.

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1-3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500-1,500 and a maximum of 1,530-8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.

Native American gene flow into Polynesia predating Easter Island settlement.

The possibility of voyaging contact between prehistoric Polynesian and Native American populations has long intrigued researchers. Proponents have pointed to the existence of New World crops, such as the sweet potato and bottle gourd, in the Polynesian archaeological record, but nowhere else outside the pre-Columbian Americas1-6, while critics have argued that these botanical dispersals need not have been human mediated7. The Norwegian explorer Thor Heyerdahl controversially suggested that prehistoric South American populations had an important role in the settlement of east Polynesia and particularly of Easter Island (Rapa Nui)2. Several limited molecular genetic studies have reached opposing conclusions, and the possibility continues to be as hotly contested today as it was when first suggested8-12. Here we analyse genome-wide variation in individuals from islands across Polynesia for signs of Native American admixture, analysing 807 individuals from 17 island populations and 15 Pacific coast Native American groups. We find conclusive evidence for prehistoric contact of Polynesian individuals with Native American individuals (around AD 1200) contemporaneous with the settlement of remote Oceania13-15. Our analyses suggest strongly that a single contact event occurred in eastern Polynesia, before the settlement of Rapa Nui, between Polynesian individuals and a Native American group most closely related to the indigenous inhabitants of present-day Colombia.

Breaking muscle: neurotoxic and myotoxic effects of Central American snake venoms and the relative efficacies of antivenom and varespladib.

BACKGROUND: The snake genera Atropoides, Cerrophidion, and Metlapilcoatlus form a clade of neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion, and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA2s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA2 inhibitor, varespladib. RESULTS: All venoms showed myotoxic and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenom ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA2 inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA2 mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA2 toxin types. CONCLUSIONS: This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms.

Evolutionary déjà vu? A case of convergent evolution in an ant-plant association.

Obligatory ant-plant symbioses often appear to be single evolutionary shifts within particular ant lineages; however, convergence can be revealed once natural history observations are complemented with molecular phylogenetics. Here, we describe a remarkable example of convergent evolution in an ant-plant symbiotic system. Exclusively arboreal, Myrmelachista species can be generalized opportunists nesting in several plant species or obligately symbiotic, live-stem nesters of a narrow set of plant species. Instances of specialization within Myrmelachista are known from northern South America and throughout Middle America. In Middle America, a diverse radiation of specialists occupies understory treelets of lowland rainforests. The morphological and behavioural uniformity of specialists suggests that they form a monophyletic assemblage, diversifying after a single origin of specialization. Using ultraconserved element phylogenomics and ancestral state reconstructions, we show that shifts from opportunistic to obligately symbiotic evolved independently in South and Middle America. Furthermore, our analyses support a remarkable case of convergence within the Middle American radiation, with two independently evolved specialist clades, arising nearly simultaneously from putative opportunistic ancestors during the late Pliocene. This repeated evolution of a complex phenotype suggests similar mechanisms behind trait shifts from opportunists to specialists, generating further questions about the selective forces driving specialization.

Parkinson's Disease Gene Screening in Familial Cases from Central and South America.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. OBJECTIVES: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. METHODS: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. RESULTS: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. CONCLUSIONS: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Exposure of protected areas in Central America to extreme weather events.

Central America and the Caribbean are regularly battered by megadroughts, heavy rainfall, heat waves, and tropical cyclones. Although 21st-century climate change is expected to increase the frequency, intensity, and duration of these extreme weather events (EWEs), their incidence in regional protected areas (PAs) remains poorly explored. We examined historical and projected EWEs across the region based on 32 metrics that describe distinct dimensions (i.e., intensity, duration, and frequency) of heat waves, cyclones, droughts, and rainfall and compared trends in PAs with trends in unprotected lands. From the early 21st century onward, exposure to EWEs increased across the region, and PAs were predicted to be more exposed to climate extremes than unprotected areas (as shown by autoregressive model coefficients at p < 0.05 significance level). This was particularly true for heat waves, which were projected to have a significantly higher average (tested by Wilcoxon tests at p < 0.01) intensity and duration, and tropical cyclones, which affected PAs more severely in carbon-intensive scenarios. PAs were also predicted to be significantly less exposed to droughts and heavy rainfall than unprotected areas (tested by Wilcoxon tests at p < 0.01). However, droughts that could threaten connectivity between PAs are increasingly common in this region. We estimated that approximately 65% of the study area will experience at least one drought episode that is more intense and longer lasting than previous droughts. Collectively, our results highlight that new conservation strategies adapted to threats associated with EWEs need to be tailored and implemented promptly. Unless urgent action is taken, significant damage may be inflicted on the unique biodiversity of the region.

Ciclones, olas de calor, sequías y lluvias intensas son eventos comunes en Centroamérica y el Caribe, cuya frecuencia, intensidad y duración se espera aumente durante el siglo XXI a causa del cambio climático. Sin embargo, en la actualidad, se desconoce cuál será la incidencia de estos eventos meteorológicos extremos (EME) dentro de las áreas protegidas. En este estudio examinamos la exposición histórica y futura a los extremos climáticos y comparamos el grado de exposición dentro y fuera de las áreas protegidas de toda la región por medio de 32 métricas que describen distintas dimensiones (intensidad, duración y frecuencia) de las olas de calor, los ciclones, las sequías y las precipitaciones. Los resultados indican que a medida que aumente el número de EME, las áreas protegidas estarán más expuestas a los extremos climáticos que las áreas no protegidas. Esto es especialmente cierto en el caso de las olas de calor, que, según las proyecciones, tendrán una intensidad y una duración medias significativamente mayores, y de los ciclones tropicales, que afectarán más gravemente a las zonas protegidas en los escenarios intensivos en carbono. Nuestros resultados también indican que las zonas protegidas estarán significativamente menos expuestas a sequías o lluvias torrenciales que las zonas no protegidas. Sin embargo, las sequías que podrían amenazar la conectividad entre áreas protegidas son cada vez más frecuentes en esta región. Se estima que aproximadamente el 65% del área de estudio experimentará al menos un episodio de sequía más intenso y duradero que las sequías anteriores. En conjunto, nuestros resultados ponen de relieve la necesidad de diseñar y aplicar con prontitud nuevas estrategias de conservación adaptadas a las amenazas asociadas a los EWE. A menos que se tomen medidas urgentes, la biodiversidad única de la región podría sufrir daños considerables.

Surgical outreach for the Americas: a self-sustainable model for partnership and education.

INTRODUCTION: It is estimated that up to 28% of global disease burden is surgical with hernias representing a unique challenge as the only definitive treatment is surgery. Surgical Outreach for the Americas (SOfA) is a nongovernmental organization focused primarily on alleviating the disease burden of inguinal and umbilical hernias in Central America. We present the experience of SOfA, a model focused on partnership and education. METHODS: SOfA was established in 2009 to help individuals recover from ailments that are obstacles to working and independent living. Over the past 15 years, SOfA has partnered with local healthcare providers in the Dominican Republic, El Salvador, Honduras, and Belize. The SOfA team consists of surgeons, surgery residents, triage physicians, an anesthesiologist, anesthetists, operating room nurses, recovery nurses, a pediatric critical care physician, sterile processing technicians, interpreters, and a team coordinator. Critical partnerships required include the CMO, internal medicine, general surgery, nursing, rural health coordinators and surgical training programs at public hospitals. RESULTS: SOfA has completed 24 trips, performing 2074 procedures on 1792 patients. 71.4% of procedures were hernia repairs. To enhance sustainability of healthcare delivery, SOfA has partnered with the local facilities through capital improvements to include OR tables, OR lights, anesthesia machines, monitors, hospital beds, stretchers, sterilizers, air conditioning units, and electrosurgical generators. A lecture series and curriculum on perioperative care, anesthesia, anatomy, and operative technique is delivered. Local surgery residents and medical students participated in patient care, learning alongside SOfA teammates. Recently, SOfA has partnered with SAGES Global Affairs Committee to implement a virtual Global Laparoscopic Advancement Program, a simulation-based laparoscopic training curriculum for surgeons in El Salvador. CONCLUSION: A sustainable partnership to facilitate surgical care in low resource settings requires longitudinal, collaborative relationships, and investments in capital improvements, education, and partnership with local healthcare providers, institutions, and training programs.

Firearm manufacturing and imports in the USA and their association to firearm homicides in Central America and the Caribbean, 1991-2019.

BACKGROUND: Firearm manufacturing and imports grew in the US during the mid-2000s. We hypothesise those increases corresponded to increased international firearms trafficking and in turn were associated with increases in firearm homicides abroad. METHODS: We used the Global Burden of Disease database to quantify annual firearm and non-firearm homicide rates in Central American and Caribbean countries, 1991-2019. We obtained US firearm manufacturing and import data from the Bureau of Alcohol, Tobacco, Firearms and Explosives. We used two-way fixed effects regressions to estimate within-country associations between homicide rates (firearm and non-firearm) and US firearm manufacturing and imports. FINDINGS: Firearm homicide rates in Central American and Caribbean countries increased from 8.38/100K population in 2004 to 17.55/100 K in 2012 and remained steady thereafter. Those surges coincided with increases in US firearm manufacturing/imports (from 4.99 million in 2004 to 13.12 million in 2012). Non-firearm homicides remained roughly constant from 1991 to 2019. Adjusted analysis showed that an annual increase of one million firearms manufactured/imported in the US corresponded to an annual increase of 1.42 (95% CI 0.62 to 2.21) firearm homicides per 100 K in Central American and Caribbean countries. The corresponding change for non-firearm homicides was -0.18 (95% CI -1.46 to 1.11). We found country-to-country variability in these effects. INTERPRETATION: Increases in US firearm manufacturing/imports were associated with increases in firearm homicide rates in Central American and Caribbean countries but not associated with non-firearm homicides. The specificity to firearm homicides suggests possible international repercussions of increased firearm manufacturing and imports in the US implications are discussed.

Solidarity through food: Coping with food insecurity among adolescent migrants in transit through Mexico and Central America.

BACKGROUND: The food choices of migrants are frequently limited by lack of access to sufficient and adequate food. Food insecurity (FI) during adolescence has potential negative health consequences, however the experiences of FI of adolescent in-transit migrants have seldom been reported. OBJECTIVE: To explore the experiences of FI of adolescent in-transit migrants and their ways of coping with it. METHODS: Qualitative study, with 19 semi-structured interviews with adolescents (ages 13-19 years), in shelters for migrants in Mexico in 2022-2023. We followed a reflexive thematic analysis strategy. RESULTS: Most participants had experienced FI during the journey, and responded by limiting intake, choosing food according to price, seeking temporary work or asking for food or money in the streets. We defined "solidarity through food" as a central theme that summarized participants' experiences of sharing food with other migrants, as givers or recipients. Solidarity through food was a response to FI, benefitting the more disadvantaged (e.g. young children, those who had been robbed). Despite their young age, interviewees took part in this, giving their food to others and restricting their intake to prioritize younger siblings. DISCUSSION/CONCLUSIONS: Solidarity through food was a form of generalized reciprocity, enacted not only among family members or friends, but extended to other migrants sharing the route. In further studies, it will be important to explore the role and nuances of food sharing as a practice of social exchange of responsibility and care, on adolescent migrants' health, and in their psychological and relational development into adulthood.

The golden age of social science.

Social science is entering a golden age, marked by the confluence of explosive growth in new data and analytic methods, interdisciplinary approaches, and a recognition that these ingredients are necessary to solve the more challenging problems facing our world. We discuss how developing a "lingua franca" can encourage more interdisciplinary research, providing two case studies (social networks and behavioral economics) to illustrate this theme. Several exemplar studies from the past 12 y are also provided. We conclude by addressing the challenges that accompany these positive trends, such as career incentives and the search for unifying frameworks, and associated best practices that can be employed in response.

Trends in Anthropometric Measurements of Internationally Adopted Children.

OBJECTIVE: The objective of this study was to describe anthropometric measures from internationally adopted children. Internationally adopted children are at risk for poor growth and development and there is no standardized growth chart evaluation for internationally adopted children due to variations in growth, genetics, and environmental exposures. METHODS: This is a retrospective chart review of 882 patients seen in an international adoption clinic between 2010 and 2017. Anthropometric measurements were converted to Z scores for weight, height, head circumference, and body mass index. RESULTS: A total of 41 countries and 16 subregions were represented. Central America, northern Africa, southern Africa, and southern Europe were the only subregions that had positive mean Z scores for weight, and southeast Asia had the lowest mean Z score for weight (n = 40, -1.76). No subregion had a positive mean Z score for height, and western Asia had the lowest overall mean Z score for height (n = 2, -2.44). Mean Z score for body mass index was positive in several subregions. CONCLUSIONS: Growth is an important predictor of health and development, and this study adds to the literature on growth patterns of internationally adopted children.

Phylogeographic patterns of Cyphocharax from trans-Andean rivers and northward expansion to lower Central America (Teleostei, Curimatidae).

Phylogenetic analyses of mitochondrial and nuclear data of 31 specimens of Cyphocharax from trans-Andean rivers support the presence of one lineage of Cyphocharax aspilos in Lago Maracaibo and three cryptic lineages of Cyphocharax magdalenae: (1) Cauca-Magdalena and Ranchería, (2) León and Atrato, and (3) Chucunaque-Tuira, Santa María, and Chiriquí basins of Central America. Results suggest that the Serranía del Perijá facilitated Late Miocene cladogenetic events, whereas post-Isthmian C. magdalenae expansion was enabled by gene flow across the lower Magdalena valley and Central American lowlands. Time-calibrated phylogenetics indicate that the C. magdalenae colonized lower Central America in the Pliocene (3.7 MYA; Ma), the divergence Atrato-Magdalena occurred in Late Pliocene (3.0 Ma) and the split Ranchería-Magdalena during the Middle Pleistocene (1.3 Ma). Updated geographic distribution data support the hypothesis that the Cordillera de Talamanca functions as a barrier to northward expansion of C. magdalenae in Central America.

INTESTINAL TYMPANY AND VOLVULUS IN CENTRAL AMERICAN RIVER TURTLES (DERMATEMYS MAWII).

Ten cases of small intestinal tympany with or without volvulus were documented in Central American river turtles (Dermatemys mawii). These turtles were under managed care at the Philadelphia Zoo in Philadelphia, PA, USA, with one case followed after transfer to a different institution. The primary clinical presentation was abnormal buoyancy in nearly all cases (9/10) and anorexia in two cases (2/10). Five of 10 turtles with suspected or radiographically confirmed small intestinal tympany recovered (5/10), whereas five cases (5/ 10) resulted in death or euthanasia. In all fatal cases (5/5), small intestinal volvulus was identified at gross necropsy, with concurrent colonic volvulus identified in 2/5 cases. Other notable necropsy findings were hepatic lipidosis (3/5) and thrombosis of intestinal or renal vasculature (2/5). In all fatal cases (5/5), there was short (1 to 2 days) clinical progression from abnormal buoyancy to death or euthanasia. In the majority of cases (6/10), an abrupt change in diet, notably the overfeeding of fresh fruit or excessive amounts of mulberry (Morus spp.) browse, or ingestion of indigestible foreign material, occurred prior to presentation. Temporary suboptimal environmental temperatures were suspected prior to the onset of clinical signs in 4/10 cases. Optimal husbandry conditions including nutrition and environmental temperature appear vital to preventing this condition. Recognition of early clinical signs of this condition, such as abnormal buoyancy and anorexia, and environmental correction or medical therapy, may prevent fatality and result in a better outcome in these cases.

Spatial scale impacts microbial community composition and distribution within and across stream ecosystems in North and Central America.

A mechanistic understanding of factors that structure spatiotemporal community composition is a major challenge in microbial ecology. Our study of microbial communities in the headwaters of three freshwater stream networks showed significant community changes at the small spatial scale of benthic habitats when compared to changes at mid- and large-spatial scales associated with stream order and catchment. Catchment (which included temperate and tropical catchments) had the strongest influence on community composition followed by habitat type (epipsammon or epilithon) and stream orders. Alpha diversity of benthic microbiomes resulted from interactions between catchment, habitat, and canopy. Epilithon contained relatively more Cyanobacteria and algae while Acidobacteria and Actinobacteria proportions were higher in epipsammic habitats. Turnover from replacement created ~60%-95% of beta diversity differences among habitats, stream orders, and catchments. Turnover within a habitat type generally decreased downstream indicating longitudinal linkages in stream networks while between habitat turnover also shaped benthic microbial community assembly. Our study suggests that factors influencing microbial community composition shift in dominance across spatial scales, with habitat dominating locally and catchment dominating globally.

Climbing mechanisms and the diversification of neotropical climbing plants across time and space.

Climbers germinate on the ground but need external support to sustain their stems, which are maintained attached to supports through modified organs, that is, climbing mechanisms. Specialized climbing mechanisms have been linked to higher diversification rates. Also, different mechanisms may have different support diameter restrictions, which might influence climbers' spatial distribution. We test these assumptions by linking climbing mechanisms to the spatiotemporal diversification of neotropical climbers. A dataset of climbing mechanisms is presented for 9071 species. WCVP was used to standardize species names, map geographical distributions, and estimate diversification rates of lineages with different mechanisms. Twiners appear concentrated in the Dry Diagonal of South America and climbers with adhesive roots in the Chocó region and Central America. However, climbing mechanisms do not significantly influence the distribution of neotropical climbers. Also, we found no strong support for correlations between specialized climbing mechanisms and higher diversification rates. Climbing mechanisms do not strongly impact the spatiotemporal diversification of neotropical climbers on a macroevolutionary scale. We argue that the climbing habit is a synnovation, meaning the spatiotemporal diversification it promotes is due to the sum effect of all the habit's traits rather than isolated traits, such as climbing mechanisms.

Unraveling the complex phylogeographic history of freshwater fishes in Lower Central America: A study of the electric fish Brachyhypopomus occidentalis.

Lower Central America (LCA) has a complex biogeographic history shaped by the rise of the Isthmus of Panama and the global climatic oscillations of the Pleistocene. These events have been crucial in structuring biodiversity in LCA, but their consequences for the distribution and partitions of genetic diversity across the region remain to be elucidated. We combined complete mitochondrial genomes and nuclear ultraconserved elements (UCEs) to study the phylogeographic history and population genetic structure of the electric fish Brachyhypopomus occidentalis in LCA. Our results are consistent with the known phylogeographic history of B. occidentalis in LCA, but we update this history in several important ways that help illuminate the phylogeographic history of freshwater fishes in the region. We provide: i) support for three waves of colonization, two of which occurred prior to the final closure of the Panama Isthmus; ii) a more precise understanding of each colonization event, with evidence for a larger footprint of the first event, as well as genetic exchange across the continental divide in subsequent events; and iii) evidence for high levels of previously unrecognized population genetic structure across LCA. This updated model of colonization and diversification of B. occidentalis consists of three waves of dispersal and colonization, which triggered the evolution of geographic breaks in both nuclear and mitochondrial genomes across LCA. These processes are tightly linked to the dynamic uplift of the Isthmus, recent volcanic activity in the region, and the sea-level oscillations of the Pleistocene. These results improve previous phylogeographic inferences regarding the distribution and diversification of freshwater fishes in LCA, and generate testable hypotheses to guide future research exploring the factors shaping biodiversity in the region.