Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying ...its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we perform high-resolution metagenomic-based analyzes of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in human populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny between microbes and hosts are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids. We find that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.
Parks are essential for protecting biodiversity and finding ways to improve park effectiveness is an important topic. We contributed to this debate by examining spatial and temporal changes in ...illegal activities in Kibale National Park, Uganda between 2006 and 2016 and used existing data to evaluate how the changes were correlated with the living conditions of people in neighboring communities, as well as patrolling effort. We explore the effectiveness of conservation strategies implemented in Kibale, by quantifying changes in the abundance of nine animal species over two to five decades. While uncertainty in such animal survey data are inherently large and it is hard to generalize across a 795‐km2 area that encompasses diverse habitat types, data suggest an increase in animal abundance in the National Park. An increase in patrolling effort by park guards over the decade was correlated with a decline in the number of traps and snares found, which suggests patrolling helped limit resource extraction from the park. The park’s edge was extensively used for illegal forest product extraction, while the setting of snares occurred more often deeper in the forest. Perhaps counter‐intuitively, increased community wealth or park‐related employment in a village next to the park were positively correlated with increased illegal forest product extraction. Overall, our results suggest that the portfolio of conservation strategies used over the last two to five decades were effective for protecting the park and its animals, although understanding the impact of these efforts on local human populations and how to mitigate any losses and suffering they sustain remains an important area of research and action. It is evident that complex social, political and economic drivers impact conservation success and more interdisciplinary studies are required to quantify and qualify these dimensions.
Finding ways to improve protected area effectiveness is a topic of importance. We contributed to this by examining spatial and temporal changes in illegal activities in Kibale National Park, Uganda between 2006 and 2016 and used existing data to evaluate how the changes were correlated with the living conditions of people in neighboring communities, as well as patrolling effort. We explore the effectiveness of conservation strategies implemented in Kibale, by quantifying changes in the abundance of nine animal species over two to five decades.
Treponema pallidum infections causing yaws disease and venereal syphilis are globally widespread in human populations, infecting hundreds of thousands and millions annually respectively; endemic ...syphilis is much less common, and pinta has not been observed in decades. We discuss controversy surrounding the origin, evolution and history of these pathogens in light of available molecular and anthropological evidence. These bacteria (or close relatives) seem to affect many wild African nonhuman primate (NHP) species, though to date only a single NHP Treponema pallidum genome has been published, hindering detection of spillover events and our understanding of potential wildlife reservoirs. Similarly, only ten genomes of Treponema pallidum infecting humans have been published, impeding a full understanding of their diversity and evolutionary history. Research efforts have been hampered by the difficulty of culturing and propagating Treponema pallidum. Here we highlight avenues of research recently opened by the coupling of hybridization capture and next-generation sequencing. We present data generated with such an approach suggesting that asymptomatic bones from NHP occasionally contain enough treponemal DNA to recover large fractions of their genomes. We expect that these methods, which naturally can be applied to modern biopsy samples and ancient human bones, will soon considerably improve our understanding of these enigmatic pathogens and lay rest to old yet unresolved controversies.
Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of ...Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10−28) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits.
Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of ...additional susceptibility loci may capture unexplained familial risk.
We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.
The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval CI = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.
This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
Abstract
Introduction
Genetic variants associated with nicotine dependence have previously been identified, primarily in European-ancestry populations. No genome-wide association studies (GWAS) have ...been reported for smoking behaviors in Hispanics/Latinos in the United States and Latin America, who are of mixed ancestry with European, African, and American Indigenous components.
Methods
We examined genetic associations with smoking behaviors in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (N = 12 741 with smoking data, 5119 ever-smokers), using ~2.3 million genotyped variants imputed to the 1000 Genomes Project phase 3. Mixed logistic regression models accounted for population structure, sampling, relatedness, sex, and age.
Results
The known region of CHRNA5, which encodes the α5 cholinergic nicotinic receptor subunit, was associated with heavy smoking at genome-wide significance (p ≤ 5 × 10–8) in a comparison of 1929 ever-smokers reporting cigarettes per day (CPD) > 10 versus 3156 reporting CPD ≤ 10. The functional variant rs16969968 in CHRNA5 had a p value of 2.20 × 10–7 and odds ratio (OR) of 1.32 for the minor allele (A); its minor allele frequency was 0.22 overall and similar across Hispanic/Latino background groups (Central American = 0.17; South American = 0.19; Mexican = 0.18; Puerto Rican = 0.22; Cuban = 0.29; Dominican = 0.19). CHRNA4 on chromosome 20 attained p < 10–4, supporting prior findings in non-Hispanics. For nondaily smoking, which is prevalent in Hispanic/Latino smokers, compared to daily smoking, loci on chromosomes 2 and 4 achieved genome-wide significance; replication attempts were limited by small Hispanic/Latino sample sizes.
Conclusions
Associations of nicotinic receptor gene variants with smoking, first reported in non-Hispanic European-ancestry populations, generalized to Hispanics/Latinos despite different patterns of smoking behavior.
Implications
We conducted the first large-scale genome-wide association study (GWAS) of smoking behavior in a US Hispanic/Latino cohort, and the first GWAS of daily/nondaily smoking in any population. Results show that the region of the nicotinic receptor subunit gene CHRNA5, which in non-Hispanic European-ancestry smokers has been associated with heavy smoking as well as cessation and treatment efficacy, is also significantly associated with heavy smoking in this Hispanic/Latino cohort. The results are an important addition to understanding the impact of genetic variants in understudied Hispanic/Latino smokers.
Objective
Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined.
Methods
Previously genome‐wide ...association study‐identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos.
Results
The C‐allele (frequency = 26%) of rs2943650 was significantly associated with higher BF% overall (β = 0.34 ± 0.11% per allele; P = 0.002) and in women (β = 0.41 ± 0.14% per C‐allele; P = 0.003), but not in men (β = 0.28 ± 0.18% per C‐allele; P = 0.11), though there was no significant sex difference. Using the inverse normal‐transformed data to compare effect sizes, it was found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (β = 0.054 ± 0.018SD vs. β = 0.008 ± 0.011SD per C‐allele; P = 0.03). The BF%‐increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high‐density lipoprotein cholesterol (P < 0.05).
Conclusions
This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared with European women.
Microbiomes impact a variety of processes including a host's ability to access nutrients and maintain health. While host species differences in microbiomes have been described across ecosystems, ...little is known about how microbiomes assemble, particularly in the ecological and social contexts in which they evolved. We examined gut microbiome composition in nine sympatric wild non-human primate (NHP) species. Despite sharing an environment and interspecific interactions, individuals harbored unique and persistent microbiomes influenced by host species, social group, and parentage, but surprisingly not by social relationships among members of a social group. We found a branching order of host-species networks constructed using the composition of their microbiomes as characters, which was incongruent with known NHP phylogenetic relationships, with chimpanzees (Pan troglodytes verus) sister to colobines, upon which they regularly prey. In contrast to phylogenetic clustering found in all monkey microbiomes, chimpanzee microbiomes were unique in that they exhibited patterns of phylogenetic overdispersion. This reflects unique ecological processes impacting microbiome composition in chimpanzees and future studies will elucidate the aspects of chimpanzee ecology, life history, and physiology that explain their unique microbiome community structure. Our study of contemporaneous microbiomes of all sympatric diurnal NHP in an ecosystem highlights the diverse dispersal routes shaping these complex communities.
Accumulating prokaryotic gene and genome sequences reveal that the exchange of genetic information through both homology-dependent recombination and horizontal (lateral) gene transfer (HGT) is far ...more important, in quantity and quality, than hitherto imagined. The traditional view, that prokaryotic evolution can be understood primarily in terms of clonal divergence and periodic selection, must be augmented to embrace gene exchange as a creative force, itself responsible for much of the pattern of similarities and differences we see between prokaryotic microbes. Rather than replacing periodic selection on genetic diversity, gene loss, and other chromosomal alterations as important players in adaptive evolution, gene exchange acts in concert with these processes to provide a rich explanatory paradigm-some of whose implications we explore here. In particular, we discuss (1) the role of recombination and HGT in giving phenotypic "coherence" to prokaryotic taxa at all levels of inclusiveness, (2) the implications of these processes for the reconstruction and meaning of "phylogeny," and (3) new views of prokaryotic adaptation and diversification based on gene acquisition and exchange.
The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2‐year‐old boy in Meliandou, Guinea. We investigated the zoonotic origins of the ...epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free‐tailed bats (Mops condylurus). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology.
Synopsis
The severe Ebola virus disease epidemic occurring in West Africa likely stems from a single zoonotic transmission event involving a 2‐year‐old boy in Meliandou, Guinea, who might have been infected by hunting or playing with insectivorous free‐tailed bats living in a nearby hollow tree.
Monitoring data show that larger wildlife did not experience a recent decline and is therefore unlikely to have served as the source for the Ebola virus disease epidemic in West Africa.
Fruit bat hunting and butchering are common activities in southern Guinea, therefore facilitating direct human contact.
Children are also exposed to insectivorous bats through hunting in and around villages.
No large colony of fruit bats exists in or nearby the index village (Meliandou).
The 2‐year‐old index case may have been infected by playing in a hollow tree housing a colony of insectivorous free‐tailed bats (Mops condylurus).
The severe Ebola virus disease epidemic occurring in West Africa likely stems from a single zoonotic transmission event involving a 2‐year‐old boy in Meliandou, Guinea, who might have been infected by hunting or playing with insectivorous free‐tailed bats living in a nearby hollow tree.
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