Several African mammals exhibit a phylogeographic pattern where closely related taxa are split between West/Central and East/Southern Africa, but their evolutionary relationships and histories remain ...controversial. Bushpigs (Potamochoerus larvatus) and red river hogs (P. porcus) are recognised as separate species due to morphological distinctions, a perceived lack of interbreeding at contact, and putatively old divergence times, but historically, they were considered conspecific. Moreover, the presence of Malagasy bushpigs as the sole large terrestrial mammal shared with the African mainland raises intriguing questions about its origin and arrival in Madagascar. Analyses of 67 whole genomes revealed a genetic continuum between the two species, with putative signatures of historical gene flow, variable F
values, and a recent divergence time (<500,000 years). Thus, our study challenges key arguments for splitting Potamochoerus into two species and suggests their speciation might be incomplete. Our findings also indicate that Malagasy bushpigs diverged from southern African populations and underwent a limited bottleneck 1000-5000 years ago, concurrent with human arrival in Madagascar. These results shed light on the evolutionary history of an iconic and widespread African mammal and provide insight into the longstanding biogeographic puzzle surrounding the bushpig's presence in Madagascar.
The blue wildebeest (Connochaetes taurinus) is a keystone species in savanna ecosystems from southern to eastern Africa, and is well known for its spectacular migrations and locally extreme ...abundance. In contrast, the black wildebeest (C. gnou) is endemic to southern Africa, barely escaped extinction in the 1900s and is feared to be in danger of genetic swamping from the blue wildebeest. Despite the ecological importance of the wildebeest, there is a lack of understanding of how its unique migratory ecology has affected its gene flow, genetic structure and phylogeography. Here, we analyze whole genomes from 121 blue and 22 black wildebeest across the genus' range. We find discrete genetic structure consistent with the morphologically defined subspecies. Unexpectedly, our analyses reveal no signs of recent interspecific admixture, but rather a late Pleistocene introgression of black wildebeest into the southern blue wildebeest populations. Finally, we find that migratory blue wildebeest populations exhibit a combination of long-range panmixia, higher genetic diversity and lower inbreeding levels compared to neighboring populations whose migration has recently been disrupted. These findings provide crucial insights into the evolutionary history of the wildebeest, and tangible genetic evidence for the negative effects of anthropogenic activities on highly migratory ungulates.
Large carnivores are generally sensitive to ecosystem changes because their specialized diet and position at the top of the trophic pyramid is associated with small population sizes. Accordingly, low ...genetic diversity at the whole-genome level has been reported for all big cat species, including the widely distributed leopard. However, all previous whole-genome analyses of leopards are based on the Far Eastern Amur leopards that live at the extremity of the species’ distribution and therefore are not necessarily representative of the whole species. We sequenced 53 whole genomes of African leopards. Strikingly, we found that the genomic diversity in the African leopard is 2- to 5-fold higher than in other big cats, including the Amur leopard, likely because of an exceptionally high effective population size maintained by the African leopard throughout the Pleistocene. Furthermore, we detected ongoing gene flow and very low population differentiation within African leopards compared with those of other big cats. We corroborated this by showing a complete absence of an otherwise ubiquitous equatorial forest barrier to gene flow. This sets the leopard apart from most other widely distributed large African mammals, including lions. These results revise our understanding of trophic sensitivity and highlight the remarkable resilience of the African leopard, likely because of its extraordinary habitat versatility and broad dietary niche.
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•African and Amur leopards have markedly different demographic trajectories•Among big cats, African leopards have the highest genetic diversity•Gene flow on a continent-wide scale maintains low genetic differentiation•Broad dietary and habitat niche likely explain the extraordinary genetic makeup
Pečnerová et al. analyze whole-genome data from 53 African leopards and identify genetic features that set the African leopard apart from the Amur leopards, as well as the other big cats. This includes long-term high effective population size and exceptionally high levels of genetic diversity and connectivity.
The repeated evolution of phenotypes provides clear evidence for the role of natural selection in driving evolutionary change. However, the evolutionary origin of repeated phenotypes can be difficult ...to disentangle as it can arise from a combination of factors such as gene flow, shared ancestral polymorphisms or mutation. Here, we investigate the presence of these evolutionary processes in the Hawaiian spiny‐leg Tetragnatha adaptive radiation, which includes four microhabitat‐specialists or ecomorphs, with different body pigmentation and size (Green, Large Brown, Maroon, and Small Brown). We investigated the evolutionary history of this radiation using 76 newly generated low‐coverage, whole‐genome resequenced samples, along with phylogenetic and population genomic tools. Considering the Green ecomorph as the ancestral state, our results suggest that the Green ecomorph likely re‐evolved once, the Large Brown and Maroon ecomorphs evolved twice and the Small Brown evolved three times. We found that the evolution of the Maroon and Small Brown ecomorphs likely involved ancestral hybridization events, while the Green and Large Brown ecomorphs likely evolved through novel mutations, despite a high rate of incomplete lineage sorting in the dataset. Our findings demonstrate that the repeated evolution of ecomorphs in the Hawaiian spiny‐leg Tetragnatha is influenced by multiple evolutionary processes.
Strong genetic structure has prompted discussion regarding giraffe taxonomy,1,2,3 including a suggestion to split the giraffe into four species: Northern (Giraffa c. camelopardalis), Reticulated ...(G. c. reticulata), Masai (G. c. tippelskirchi), and Southern giraffes (G. c. giraffa).4,5,6 However, their evolutionary history is not yet fully resolved, as previous studies used a simple bifurcating model and did not explore the presence or extent of gene flow between lineages. We therefore inferred a model that incorporates various evolutionary processes to assess the drivers of contemporary giraffe diversity. We analyzed whole-genome sequencing data from 90 wild giraffes from 29 localities across their current distribution. The most basal divergence was dated to 280 kya. Genetic differentiation, FST, among major lineages ranged between 0.28 and 0.62, and we found significant levels of ancient gene flow between them. In particular, several analyses suggested that the Reticulated lineage evolved through admixture, with almost equal contribution from the Northern lineage and an ancestral lineage related to Masai and Southern giraffes. These new results highlight a scenario of strong differentiation despite gene flow, providing further context for the interpretation of giraffe diversity and the process of speciation in general. They also illustrate that conservation measures need to target various lineages and sublineages and that separate management strategies are needed to conserve giraffe diversity effectively. Given local extinctions and recent dramatic declines in many giraffe populations, this improved understanding of giraffe evolutionary history is relevant for conservation interventions, including reintroductions and reinforcements of existing populations.
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•Giraffes show exceptional genetic structure despite lack of physical barriers•Giraffes have a complex evolutionary history, with high levels of gene flow•Reticulated giraffes are a hybrid lineage•For effective conservation, diversity within giraffes needs to be taken into account
Giraffes consist of four major lineages, which show strong divergence despite being geographically close. Following analyses of whole genomes from 90 wild giraffes from throughout their range, Bertola et al. show that the evolutionary history of giraffes is complex and marked by major gene flow, in particular affecting Reticulated giraffes.
Perturbation of lipid homoeostasis is a major risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. We aimed to identify genetic variants affecting lipid levels, and ...thereby risk of CVD, in Greenlanders. Genome-wide association studies (GWAS) of six blood lipids, triglycerides, LDL-cholesterol, HDL-cholesterol, total cholesterol, as well as apolipoproteins A1 and B, were performed in up to 4473 Greenlanders. For genome-wide significant variants, we also tested for associations with additional traits, including CVD events. We identified 11 genome-wide significant loci associated with lipid traits. Most of these loci were already known in Europeans, however, we found a potential causal variant near PCSK9 (rs12117661), which was independent of the known PCSK9 loss-of-function variant (rs11491147). rs12117661 was associated with lower LDL-cholesterol (β
(SE) = -0.22 (0.03), p = 6.5 × 10
) and total cholesterol (-0.17 (0.03), p = 1.1 × 10
) in the Greenlandic study population. Similar associations were observed in Europeans from the UK Biobank, where the variant was also associated with a lower risk of CVD outcomes. Moreover, rs12117661 was a top eQTL for PCSK9 across tissues in European data from the GTEx portal, and was located in a predicted regulatory element, supporting a possible causal impact on PCSK9 expression. Combined, the 11 GWAS signals explained up to 16.3% of the variance of the lipid traits. This suggests that the genetic architecture of lipid levels in Greenlanders is different from Europeans, with fewer variants explaining the variance.
Genomic studies of species threatened by extinction are providing crucial information about evolutionary mechanisms and genetic consequences of population declines and bottlenecks. However, to ...understand how species avoid the extinction vortex, insights can be drawn by studying species that thrive despite past declines. Here, we studied the population genomics of the muskox (Ovibos moschatus), an Ice Age relict that was at the brink of extinction for thousands of years at the end of the Pleistocene yet appears to be thriving today. We analysed 108 whole genomes, including present‐day individuals representing the current native range of both muskox subspecies, the white‐faced and the barren‐ground muskox (O. moschatus wardi and O. moschatus moschatus) and a ~21,000‐year‐old ancient individual from Siberia. We found that the muskox' demographic history was profoundly shaped by past climate changes and post‐glacial re‐colonizations. In particular, the white‐faced muskox has the lowest genome‐wide heterozygosity recorded in an ungulate. Yet, there is no evidence of inbreeding depression in native muskox populations. We hypothesize that this can be explained by the effect of long‐term gradual population declines that allowed for purging of strongly deleterious mutations. This study provides insights into how species with a history of population bottlenecks, small population sizes and low genetic diversity survive against all odds.
The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb ...sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency.
The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings.
Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (β standard error, –2.0 0.5 kg/m2; P = 3.1 × 10–5), body weight (–4.8 1.4 kg; P = 5.1 × 10–4), fat percentage (–3.3% 1.0%; P = 3.7 × 10–4), fasting triglyceride (–0.27 0.07 mmol/L; P = 2.3 × 10–6), and remnant cholesterol (–0.11 0.03 mmol/L; P = 4.2 × 10–5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (β standard error, 0.056 0.002 mmol/L; P = 2.1 × 10–26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test.
These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate.
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A sucrase-isomaltase loss-of-function variant was associated with a markedly healthier metabolic profile in Greenlandic adults, suggesting that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health.
Abstract
The advancements of high-throughput genomics have unveiled much about the human genome highlighting the importance of variations between individuals and their contribution to disease. Even ...though numerous software have been developed to make sense of large genomics datasets, a major short falling of these has been the inability to cope with repetitive regions, specifically to validate structural variants and accordingly assess their role in disease. Here we describe our program STEAK, a massively parallel software designed to detect chimeric reads in high-throughput sequencing data for a broad number of applications such as identifying presence/absence, as well as discovery of transposable elements (TEs), and retroviral integrations. We highlight the capabilities of STEAK by comparing its efficacy in locating HERV-K HML-2 in clinical whole genome projects, target enrichment sequences, and in the 1000 Genomes CEU Trio to the performance of other TE and virus detecting tools. We show that STEAK outperforms other software in terms of computational efficiency, sensitivity, and specificity. We demonstrate that STEAK is a robust tool, which allows analysts to flexibly detect and evaluate TE and retroviral integrations in a diverse range of sequencing projects for both research and clinical purposes.
The genetic disease architecture of Inuit includes a large number of common high-impact variants. Identification of such variants contributes to our understanding of the genetic aetiology of diseases ...and improves global equity in genomic personalised medicine. We aimed to identify and characterise novel variants in genes associated with Maturity Onset Diabetes of the Young (MODY) in the Greenlandic population.
Using combined data from Greenlandic population cohorts of 4497 individuals, including 448 whole genome sequenced individuals, we screened 14 known MODY genes for previously identified and novel variants. We functionally characterised an identified novel variant and assessed its association with diabetes prevalence and cardiometabolic traits and population impact.
We identified a novel variant in the known MODY gene HNF1A with an allele frequency of 1.9% in the Greenlandic Inuit and absent elsewhere. Functional assays indicate that it prevents normal splicing of the gene. The variant caused lower 30-min insulin (β = −232 pmol/L, βSD = −0.695, P = 4.43 × 10−4) and higher 30-min glucose (β = 1.20 mmol/L, βSD = 0.441, P = 0.0271) during an oral glucose tolerance test. Furthermore, the variant was associated with type 2 diabetes (OR 4.35, P = 7.24 × 10−6) and HbA1c (β = 0.113 HbA1c%, βSD = 0.205, P = 7.84 × 10−3). The variant explained 2.5% of diabetes variance in Greenland.
The reported variant has the largest population impact of any previously reported variant within a MODY gene. Together with the recessive TBC1D4 variant, we show that close to 1 in 5 cases of diabetes (18%) in Greenland are associated with high-impact genetic variants compared to 1–3% in large populations.
Novo Nordisk Foundation, Independent Research Fund Denmark, and Karen Elise Jensen's Foundation.
HNF1A-mi pinngoqqaammi allannguut suussusersineqarlaaq, pinngoqqaatinik allannguinermut sunniuteqartoq, Kalaallit Nunaanni diabetesimik nappaateqarnermut annertuumik sunniutilik.
Naggueqatigiit Inuit akornanni nappaatit pinngoqqaatikkut katitigaanerat, pinngoqqaatikkut allannguutaagajuttunik amerlaqisunik nappaateqalersinnaanermut annertuumik sunniuteqartunik akoqarput. Allannguutinik taamaattunik suussusersineq, pinngoqqaatinik nappaatinut patsisaasunik paasinnititseqataavoq, nunarsuarmilu nakorsaanermut nappatinillu suussusersiniaanermut atatillugu pinngoqqaatinik kingornuttakkanik misissuinermi naligiinnerulersitsilluni. Misissuinermi matumani, pinngoqqaatini allannguutinik, diabetesimik pinngoqqaammi akornuteqarnermik patsiseqartumi Maturity Onset Diabetes of the Young (MODY), Kalaallit Nunaanni innuttaasuni nalinginnaanerpaamit ilisimaneqartunik suussusersinissaq naliliinissarlu siunertaavoq.
Innuttaasut katillugit 4497-it taakkunannga 448-it, pinngoqqaataat kingornuttakkat, pinngoqqaateqarfik tamakkerlugu misissukkat, kalaallit peqqissusaannik misissuisitsinernit paasissutissanik ataqatigiissitanik atuinikkut, pinngoqqaatit MODY-it ilisimaneqartut 14-it, ilisimaneqartunik ilisimaneqanngitsunillu allannguuteqarnersut misissorpagut. Allannguutip suussusersineqarlaap qanoq ittuuneranik nassuiaavugut, diabetisillu atugaaneranut uummalluuteqarnermullu inooriaatsimik patsiseqartumut ilisarnaatit innuttaasunilu diabetesimut atassutaa misissoqqissaarlugit.
Naggueqatigiinni kalaallini pinngoqqaammi allannguut ilisimaneqartumi MODY- mi HNF1A maannamut suususersineqanngitsoq, pinngoqqaammi allannguut 1.9%-imik akulikissusilik, inuiannilu allani nassassaanngitsoq suussusersivarput. Pinngoqqaammi allannguutip pinngoqqaatip pissusissamisut allangornissaanik akornusiinera qanoq ittuuneranik misissuinerit paasinarsisippaat. Sukkumik arrortitsisinnaanermut misissuinermi pinngoqqaammi allannguutip 30-min insulinip appasinnerusarnera (β = −232 pmol/L, βSD = −0.695, P = 4.43 × 10−4) 30-min glucose-llu qaffasinnerunera (β = 1.20 mmol/L, βSD = 0.441, P = 0.0271) nassataraa. Allannguut type 2 diabetesimut (OR 4.35, P = 7.24 × 10−6) kiisalu HbA1c (β = 0.113 HbA1c%, βSD = 0.205, P = 7.84 × 10−3) atassuteqarpoq. Allannguutip Kalaallit Nunaanni diabetesimut allannguutip 2.5%-ia nassuiarpaa.
Pinngoqqaammi allannguut nalunaarutigineqartoq pinngoqaammi MODY-mi allannguummit siornatigut nassuiarneqartumit innuttaasunut annertunerusumik sunniuteqarpoq. Pinngoqqaammi allannguut kinguaanit kingornunneqarsinnaasoq TBC1D4 ilanngullugu, Kalaallit Nunaanni diabetesimik nappaateqartut tallimaappata ataatsip pallingajattup (18%)- innuttaasunut amerlasuunut 1-3%-inut sanilliullugit-pinngoqqaammi allannguutinut nappaateqalernissamut annertuumik sunniutilinnut atassuteqarnera takutipparput.
Novo Nordisk Fonden, Danmarks Frie Forskningsfond kiisalu Karen Elise Jensens Fond.”
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