Long COVID Among Kidney Transplant Recipients Appears to Be Attenuated During the Omicron Predominance.

BACKGROUND: Omicron variant has been associated with milder cases of COVID-19 among kidney transplant recipients. However, little is known about postacute sequelae, referred to as Long COVID. METHODS: Prospective, single-center cohort study investigating prevalence and risk factors for Long COVID among kidney transplant recipients during the omicron predominance in Brazil. The analysis included adult patients with confirmed SARS-CoV-2 infection between January 5, 2022, and July 18, 2022, were alive, had a functioning kidney transplant 3 mo after symptom onset, and answered a telephonic survey about physical complains of Long COVID. RESULTS: From the 1529 eligible, 602 (39%) patients responded the survey. Sixteen percent reported a previous SARS-CoV-2 infection, and 85% had been fully vaccinated. The prevalence of Long COVID was 52%, with the most common complaints being weakness (46%), myalgia (41%), dizziness (33%), and headache (31%). Among employed patients, 94% were able to resume their normal work activities. In multivariable analysis, female gender (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.51-3.02; P < 0.0001), previous SARS-CoV-2 infection (HR, 3.55; 95% CI, 1.91-6.60; P < 0.0001), fatigue (HR, 2.32; 95% CI, 1.18-4.55; P = 0.014), myalgia (HR, 1.48; 95% CI, 1.03-2.15; P = 0.036) during the acute phase, and hospitalization because of COVID-19 (HR, 1.71; 95% CI, 1.06-2.76; P = 0.028) were independently associated with Long COVID. CONCLUSIONS: In the "omicron era," Long COVID among kidney transplant recipients exhibited milder characteristics and had a less significant impact on their ability to resume normal life activities. The risk factors for persistent symptoms were similar to those observed in the general population except for the vaccination status, underscoring the importance of closer monitoring in special subgroups.

Imputation of ancient human genomes.

Due to postmortem DNA degradation and microbial colonization, most ancient genomes have low depth of coverage, hindering genotype calling. Genotype imputation can improve genotyping accuracy for low-coverage genomes. However, it is unknown how accurate ancient DNA imputation is and whether imputation introduces bias to downstream analyses. Here we re-sequence an ancient trio (mother, father, son) and downsample and impute a total of 43 ancient genomes, including 42 high-coverage (above 10x) genomes. We assess imputation accuracy across ancestries, time, depth of coverage, and sequencing technology. We find that ancient and modern DNA imputation accuracies are comparable. When downsampled at 1x, 36 of the 42 genomes are imputed with low error rates (below 5%) while African genomes have higher error rates. We validate imputation and phasing results using the ancient trio data and an orthogonal approach based on Mendel's rules of inheritance. We further compare the downstream analysis results between imputed and high-coverage genomes, notably principal component analysis, genetic clustering, and runs of homozygosity, observing similar results starting from 0.5x coverage, except for the African genomes. These results suggest that, for most populations and depths of coverage as low as 0.5x, imputation is a reliable method that can improve ancient DNA studies.

High Prevalence of Long-COVID Among Kidney Transplant Recipients: A Longitudinal Cohort Study.

BACKGROUND: Kidney transplant recipients are at a higher risk to develop more severe clinical forms of coronavirus disease 2019 (COVID-19), perhaps increasing the risk of presenting its long-term clinical complications, labeled as Long-COVID. METHODS: This single-center, observational, prospective study included adult kidney transplant recipients with COVID-19 confirmed by reverse transcription polymerase chain reaction between March 20, 2020, and May 31, 2021, who were alive and with functioning graft 3 mo after the onset of symptoms. The prevalence of Long-COVID was investigated by a phone survey using a structured questionnaire of organic symptoms. Adjusted multivariable logistic regression models were used to investigate independent risk factors. RESULTS: Of 1741 patients who developed COVID-19, 465 died, and 37 returned to dialysis. Of the 1239 eligible patients, 780 (63%) answered the survey during the window period. The mean age was 48 ± 12 y, 41% were women, and the mean time from transplantation was 8 ± 6 y. During acute illness, 45% needed hospitalization. Long-COVID was identified in 214 (27%) of the subjects, with body aches being the most prevalent symptom (44%). Of 233 who provided working status, 17% did not return to work within 3 mo. No baseline characteristics or infection-related variables predicted Long-COVID; actually, the number of symptoms in the acute illness was the only independent risk factor identified (hazard ratio, 1.12; 95% confidence interval, 1.02-1.22). CONCLUSION: In this cohort of kidney transplant recipients, Long-COVID was prevalent and associated with a reduced return to work. The burden of acute phase symptoms was the only risk factor associated with Long-COVID.

Integrative approaches to dispersing science: A case study of March Mammal Madness.

OBJECTIVES: Public engagement is increasingly viewed as an important pillar of scientific scholarship. For early career and established scholars, navigating the mosaic landscape of public education and science communication, noted for rapid "ecological" succession, can be daunting. Moreover, academics are characterized by diverse skills, motivations, values, positionalities, and temperaments that may differentially incline individuals to particular public translation activities. METHODS: Here we briefly contextualize engagement activities within a scholarly portfolio, describe the use of one public education program-March Mammal Madness (MMM)- to highlight approaches to science communication, and explore essential elements and practical considerations for creating and sustaining outreach pursuits in tandem with other scholarly activities. RESULTS: MMM, an annual simulated tournament of living and fossil animal taxa, has reached hundreds of thousands of learners since 2013. This program has provided a platform to communicate research findings from biology and anthropology and showcase numerous scholars in these fields. MMM has leveraged tournament devices to intentionally address topics of climate change, capitalist environmental degradation, academic sexism, and racist settler-colonialism. The tournament, however, has also perpetuated implicit biases that need disrupting. CONCLUSIONS: By embracing reflexive, self-interrogative, and growth attitudes, the tournament organizers iteratively refine and improve this public science education program to better align our activities with our values and goals. Our experiences with MMM suggest that dispersing science is most sustainable when we combine ancestral adaptations for cooperation, community, and storytelling with good-natured competition in the context of shared experiences and shared values.

The genomic history of the Aegean palatial civilizations.

The Cycladic, the Minoan, and the Helladic (Mycenaean) cultures define the Bronze Age (BA) of Greece. Urbanism, complex social structures, craft and agricultural specialization, and the earliest forms of writing characterize this iconic period. We sequenced six Early to Middle BA whole genomes, along with 11 mitochondrial genomes, sampled from the three BA cultures of the Aegean Sea. The Early BA (EBA) genomes are homogeneous and derive most of their ancestry from Neolithic Aegeans, contrary to earlier hypotheses that the Neolithic-EBA cultural transition was due to massive population turnover. EBA Aegeans were shaped by relatively small-scale migration from East of the Aegean, as evidenced by the Caucasus-related ancestry also detected in Anatolians. In contrast, Middle BA (MBA) individuals of northern Greece differ from EBA populations in showing ∼50% Pontic-Caspian Steppe-related ancestry, dated at ca. 2,600-2,000 BCE. Such gene flow events during the MBA contributed toward shaping present-day Greek genomes.

March Mammal Madness and the power of narrative in science outreach.

March Mammal Madness is a science outreach project that, over the course of several weeks in March, reaches hundreds of thousands of people in the United States every year. We combine four approaches to science outreach - gamification, social media platforms, community event(s), and creative products - to run a simulated tournament in which 64 animals compete to become the tournament champion. While the encounters between the animals are hypothetical, the outcomes rely on empirical evidence from the scientific literature. Players select their favored combatants beforehand, and during the tournament scientists translate the academic literature into gripping "play-by-play" narration on social media. To date ~1100 scholarly works, covering almost 400 taxa, have been transformed into science stories. March Mammal Madness is most typically used by high-school educators teaching life sciences, and we estimate that our materials reached ~1% of high-school students in the United States in 2019. Here we document the intentional design, public engagement, and magnitude of reach of the project. We further explain how human psychological and cognitive adaptations for shared experiences, social learning, narrative, and imagery contribute to the widespread use of March Mammal Madness.

ACE2 diversity in placental mammals reveals the evolutionary strategy of SARS-CoV-2.

The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to host-cell infection. We performed a comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses for analysis in more detail. Our results reveal a relatively high diversity of ACE2 between placental mammal species, while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites. A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans. We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts. Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors.

ACE2 diversity in placental mammals reveals the evolutionary strategy of SARS-CoV-2

The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to the host-cell infection. We perform comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses to analyze in more detail. Our results reveal a relatively high diversity of ACE2 between placental mammal species while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites. A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans. We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts. Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors.

Genomic insight into the origins and dispersal of the Brazilian coastal natives.

In the 15th century, ∼900,000 Native Americans, mostly Tupí speakers, lived on the Brazilian coast. By the end of the 18th century, the coastal native populations were declared extinct. The Tupí arrived on the east coast after leaving the Amazonian basin ∼2,000 y before present; however, there is no consensus on how this migration occurred: toward the northern Amazon and then directly to the Atlantic coast, or heading south into the continent and then migrating to the coast. Here we leveraged genomic data from one of the last remaining putative representatives of the Tupí coastal branch, a small, admixed, self-reported Tupiniquim community, as well as data of a Guaraní Mbyá native population from Southern Brazil and of three other native populations from the Amazonian region. We demonstrated that the Tupiniquim Native American ancestry is not related to any extant Brazilian Native American population already studied, and thus they could be considered the only living representatives of the extinct Tupí branch that used to settle the Atlantic Coast of Brazil. Furthermore, these data show evidence of a direct migration from Amazon to the Northeast Coast in pre-Columbian time, giving rise to the Tupí Coastal populations, and a single distinct migration southward that originated the Guaraní people from Brazil and Paraguay. This study elucidates the population dynamics and diversification of the Brazilian natives at a genomic level, which was made possible by recovering data from the Brazilian coastal population through the genomes of mestizo individuals.

Understanding 6th-century barbarian social organization and migration through paleogenomics.

Despite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungary and Northern Italy) that have been previously associated with the Longobards, a barbarian people that ruled large parts of Italy for over 200 years after invading from Pannonia in 568 CE. Our dense cemetery-based sampling revealed that each cemetery was primarily organized around one large pedigree, suggesting that biological relationships played an important role in these early medieval societies. Moreover, we identified genetic structure in each cemetery involving at least two groups with different ancestry that were very distinct in terms of their funerary customs. Finally, our data are consistent with the proposed long-distance migration from Pannonia to Northern Italy.

Correction: The population genetics of human disease: The case of recessive, lethal mutations.

[This corrects the article DOI: 10.1371/journal.pgen.1006915.].

Searching for ancient balanced polymorphisms shared between Neanderthals and Modern Humans.

Hominin evolution is characterized by adaptive solutions often rooted in behavioral and cognitive changes. If balancing selection had an important and long-lasting impact on the evolution of these traits, it can be hypothesized that genes associated with them should carry an excess of shared polymorphisms (trans- SNPs) across recent Homo species. In this study, we investigate the role of balancing selection in human evolution using available exomes from modern (Homo sapiens) and archaic humans (H. neanderthalensis and Denisovan) for an excess of trans-SNP in two gene sets: one associated with the immune system (IMMS) and another one with behavioral system (BEHS). We identified a significant excess of trans-SNPs in IMMS (N=547), of which six of these located within genes previously associated with schizophrenia. No excess of trans-SNPs was found in BEHS, but five genes in this system harbor potential signals for balancing selection and are associated with psychiatric or neurodevelopmental disorders. Our approach evidenced recent Homo trans-SNPs that have been previously implicated in psychiatric diseases such as schizophrenia, suggesting that a genetic repertoire common to the immune and behavioral systems could have been maintained by balancing selection starting before the split between archaic and modern humans.

Searching for ancient balanced polymorphisms shared between Neanderthals and Modern Humans

Abstract Hominin evolution is characterized by adaptive solutions often rooted in behavioral and cognitive changes. If balancing selection had an important and long-lasting impact on the evolution of these traits, it can be hypothesized that genes associated with them should carry an excess of shared polymorphisms (trans- SNPs) across recent Homo species. In this study, we investigate the role of balancing selection in human evolution using available exomes from modern (Homo sapiens) and archaic humans (H. neanderthalensis and Denisovan) for an excess of trans-SNP in two gene sets: one associated with the immune system (IMMS) and another one with behavioral system (BEHS). We identified a significant excess of trans-SNPs in IMMS (N=547), of which six of these located within genes previously associated with schizophrenia. No excess of trans-SNPs was found in BEHS, but five genes in this system harbor potential signals for balancing selection and are associated with psychiatric or neurodevelopmental disorders. Our approach evidenced recent Homo trans-SNPs that have been previously implicated in psychiatric diseases such as schizophrenia, suggesting that a genetic repertoire common to the immune and behavioral systems could have been maintained by balancing selection starting before the split between archaic and modern humans.

The population genetics of human disease: The case of recessive, lethal mutations.

Do the frequencies of disease mutations in human populations reflect a simple balance between mutation and purifying selection? What other factors shape the prevalence of disease mutations? To begin to answer these questions, we focused on one of the simplest cases: recessive mutations that alone cause lethal diseases or complete sterility. To this end, we generated a hand-curated set of 417 Mendelian mutations in 32 genes reported to cause a recessive, lethal Mendelian disease. We then considered analytic models of mutation-selection balance in infinite and finite populations of constant sizes and simulations of purifying selection in a more realistic demographic setting, and tested how well these models fit allele frequencies estimated from 33,370 individuals of European ancestry. In doing so, we distinguished between CpG transitions, which occur at a substantially elevated rate, and three other mutation types. Intriguingly, the observed frequency for CpG transitions is slightly higher than expectation but close, whereas the frequencies observed for the three other mutation types are an order of magnitude higher than expected, with a bigger deviation from expectation seen for less mutable types. This discrepancy is even larger when subtle fitness effects in heterozygotes or lethal compound heterozygotes are taken into account. In principle, higher than expected frequencies of disease mutations could be due to widespread errors in reporting causal variants, compensation by other mutations, or balancing selection. It is unclear why these factors would have a greater impact on disease mutations that occur at lower rates, however. We argue instead that the unexpectedly high frequency of disease mutations and the relationship to the mutation rate likely reflect an ascertainment bias: of all the mutations that cause recessive lethal diseases, those that by chance have reached higher frequencies are more likely to have been identified and thus to have been included in this study. Beyond the specific application, this study highlights the parameters likely to be important in shaping the frequencies of Mendelian disease alleles.

Genetic signature of natural selection in first Americans.

When humans moved from Asia toward the Americas over 18,000 y ago and eventually peopled the New World they encountered a new environment with extreme climate conditions and distinct dietary resources. These environmental and dietary pressures may have led to instances of genetic adaptation with the potential to influence the phenotypic variation in extant Native American populations. An example of such an event is the evolution of the fatty acid desaturases (FADS) genes, which have been claimed to harbor signals of positive selection in Inuit populations due to adaptation to the cold Greenland Arctic climate and to a protein-rich diet. Because there was evidence of intercontinental variation in this genetic region, with indications of positive selection for its variants, we decided to compare the Inuit findings with other Native American data. Here, we use several lines of evidence to show that the signal of FADS-positive selection is not restricted to the Arctic but instead is broadly observed throughout the Americas. The shared signature of selection among populations living in such a diverse range of environments is likely due to a single and strong instance of local adaptation that took place in the common ancestral population before their entrance into the New World. These first Americans peopled the whole continent and spread this adaptive variant across a diverse set of environments.

Variation in the molecular clock of primates.

Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid-NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​.

Detection of convergent genome-wide signals of adaptation to tropical forests in humans.

Tropical forests are believed to be very harsh environments for human life. It is unclear whether human beings would have ever subsisted in those environments without external resources. It is therefore possible that humans have developed recent biological adaptations in response to specific selective pressures to cope with this challenge. To understand such biological adaptations we analyzed genome-wide SNP data under a Bayesian statistics framework, looking for outlier markers with an overly large extent of differentiation between populations living in a tropical forest, as compared to genetically related populations living outside the forest in Africa and the Americas. The most significant positive selection signals were found in genes related to lipid metabolism, the immune system, body development, and RNA Polymerase III transcription initiation. The results are discussed in the light of putative tropical forest selective pressures, namely food scarcity, high prevalence of pathogens, difficulty to move, and inefficient thermoregulation. Agreement between our results and previous studies on the pygmy phenotype, a putative prototype of forest adaptation, were found, suggesting that a few genetic regions previously described as associated with short stature may be evolving under similar positive selection in Africa and the Americas. In general, convergent evolution was less pervasive than local adaptation in one single continent, suggesting that Africans and Amerindians may have followed different routes to adapt to similar environmental selective pressures.

Differing evolutionary histories of the ACTN3*R577X polymorphism among the major human geographic groups.

It has been proposed that the functional ACTN3*R577X polymorphism might have evolved due to selection in Eurasian human populations. To test this possibility we surveyed all available population-based data for this polymorphism and performed a comprehensive evolutionary analysis of its genetic diversity, in order to assess the action of adaptive and random mechanisms on its variation across human geographical distribution. The derived 577X allele increases in frequency with distance from Africa, reaching the highest frequencies on the American continent. Positive selection, detected by an extended haplotype homozygosisty test, was consistent only with the Eurasian data, but simulations with neutral models could not fully explain the results found in the American continent. It is possible that particularities of Native American population structure could be responsible for the observed allele frequencies, which would have resulted from a complex interaction between selective and random factors.

Brazilian quilombos: A repository of Amerindian alleles.

OBJECTIVES: As a consequence of colonization of the Americas and decimation of the native population, an important portion of autochthonous genetic variation has been lost. However, some alleles have been incorporated into the growing populations of admixed mestizos. In this study, we evaluated the potential of African-derived communities in Brazil to be repositories of Amerindian alleles and, by extension, a source of information on American prehistory. METHODS: In this study, we describe the genetic variation of 15 ancestry informative markers (AIMs) of autosomal origin in two quilombos, Brazilian populations mainly of African descent, Santo Antônio do Guaporé (SAG; N = 31), and Santiago do Iguape (STI; N = 37). We compared the AIMs from these populations to those of other African-Brazilian populations, and to the Distrito Federal (N = 168), an urban population representative of Brazilian genetic diversity. RESULTS: By admixture analysis, we found that the SAG and STI communities have a much higher proportion (over 40%) of Amerindian contribution to their gene pools than other admixed Brazilian populations, in addition to marked African contributions. CONCLUSIONS: These results identify two living African-Brazilian populations that carry unique and important genetic information regarding Amerindian history. These populations will be extremely valuable in future investigations into American pre-history and Native American evolutionary dynamics.

A bayesian approach to genome/linguistic relationships in native South Americans.

The relationship between the evolution of genes and languages has been studied for over three decades. These studies rely on the assumption that languages, as many other cultural traits, evolve in a gene-like manner, accumulating heritable diversity through time and being subjected to evolutionary mechanisms of change. In the present work we used genetic data to evaluate South American linguistic classifications. We compared discordant models of language classifications to the current Native American genome-wide variation using realistic demographic models analyzed under an Approximate Bayesian Computation (ABC) framework. Data on 381 STRs spread along the autosomes were gathered from the literature for populations representing the five main South Amerindian linguistic groups: Andean, Arawakan, Chibchan-Paezan, Macro-Jê, and Tupí. The results indicated a higher posterior probability for the classification proposed by J.H. Greenberg in 1987, although L. Campbell's 1997 classification cannot be ruled out. Based on Greenberg's classification, it was possible to date the time of Tupí-Arawakan divergence (2.8 kya), and the time of emergence of the structure between present day major language groups in South America (3.1 kya).