Natural selection for the Duffy-null allele in the recently admixed people of Madagascar

While gene flow between distantly related populations is increasingly recognized as a potentially important source of adaptive genetic variation for humans, fully characterized examples are rare. In addition, the role that natural selection for resistance to vivax malaria may have played in the extreme distribution of the protective Duffy-null allele, which is nearly completely fixed in mainland sub-Saharan Africa and absent elsewhere, is controversial. We address both these issues by investigating the evolution of the Duffy-null allele in the Malagasy, a recently admixed population with major ancestry components from both East Asia and mainland sub-Saharan Africa. We used genome-wide genetic data and extensive computer simulations to show that the high frequency of the Duffy-null allele in Madagascar can only be explained in the absence of positive natural selection under extreme demographic scenarios involving high genetic drift. However, the observed genomic single nucleotide polymorphism diversity in the Malagasy is incompatible with such extreme demographic scenarios, indicating that positive selection for the Duffy-null allele best explains the high frequency of the allele in Madagascar. We estimate the selection coefficient to be 0.066. Because vivax malaria is endemic to Madagascar, this result supports the hypothesis that malaria resistance drove fixation of the Duffy-null allele in mainland sub-Saharan Africa.

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Estimating the timing of multiple admixture pulses during local ancestry inference

10.1101/314617 ◽

2018 ◽

Author(s):

Paloma Medina ◽

Bryan Thornlow ◽

Rasmus Nielsen ◽

Russell Corbett-Detig

Keyword(s):

Biological Process ◽

Genetic Material ◽

Simulated Data ◽

Sub Saharan Africa ◽

African Populations ◽

Fundamental Biological Process ◽

Admixed Population ◽

Sub Saharan ◽

Local Ancestry Inference ◽

Admixture Event

ABSTRACTAdmixture, the mixing of genetically distinct populations, is increasingly recognized as a fundamental biological process. One major goal of admixture analyses is to estimate the timing of admixture events. Whereas most methods today can only detect the most recent admixture event, here we present coalescent theory and associated software that can be used to estimate the timing of multiple admixture events in an admixed population. We extensively validate this approach and evaluate the conditions under which it can succesfully distinguish one from two-pulse admixture models. We apply our approach to real and simulated data of Drosophila melanogaster. We find evidence of a single very recent pulse of cosmopolitan ancestry contributing to African populations as well as evidence for more ancient admixture among genetically differentiated populations in sub-Saharan Africa. These results suggest our method can quantify complex admixture histories involving genetic material introduced by multiple discrete admixture pulses. The new method facilitates the exploration of admixture and its contribution to adaptation, ecological divergence, and speciation.

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Methylome-wide analysis reveals epigenetic marks associated with resistance to tuberculosis in HIV-infected individuals from East Africa

10.1101/2020.07.14.20153395 ◽

2020 ◽

Author(s):

Catherine Stein ◽

Penelope Bencheck ◽

Jacquelaine Bartlett ◽

Robert P Igo ◽

Rafal S Sobota ◽

...

Keyword(s):

Genome Wide Association Study ◽

Sub Saharan Africa ◽

Chromosome 1 ◽

Chromosome 2 ◽

Chromosome 5 ◽

Epigenetic Marks ◽

Genome Wide ◽

A Genome ◽

Immunodeficiency Virus ◽

Sub Saharan

Background: Tuberculosis (TB) is the most deadly infectious disease globally and highly prevalent in the developing world, especially sub-Saharan Africa. Even though a third of humans are exposed to Myocbacterium tuberculosis (Mtb), most infected immunocompetent individuals do not develop active TB. In contrast, for individuals infected with both TB and the human immunodeficiency virus (HIV), the risk of active disease is 10% or more per year. Previously, we identified in a genome-wide association study a region on chromosome 5 that was associated with resistance to TB. This region included epigenetic marks that could influence gene regulation so we hypothesized that HIV-infected individuals exposed to Mtb, who remain disease free, carry epigenetic changes that strongly protect them from active TB. To test this hypothesis, we conducted a methylome-wide study in HIV-infected, TB-exposed cohorts from Uganda and Tanzania. Results: In 221 HIV-infected adults from Uganda and Tanzania, we identified 3 regions of interest that included markers that were differentially methylated between TB cases and LTBI controls, that also included methylation QTLs and associated SNPs: chromosome 1 (RNF220, p=4x10-5), chromosome 2 (between COPS8 and COL6A3 genes, p=2.7x10-5), and chromosome 5 (CEP72, p=1.3x10-5). These methylation results colocalized with associated SNPs, methylation QTLs, and methylation x SNP interaction effects. These markers were in regions with regulatory markers for cells involved in TB immunity and/or lung. Conclusion: Epigenetic regulation is a potential biologic factor underlying resistance to TB in immunocompromised individuals that can act in conjunction with genetic variants.

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Ancient DNA reveals a multistep spread of the first herders into sub-Saharan Africa

Science ◽

10.1126/science.aaw6275 ◽

2019 ◽

Vol 365 (6448) ◽

pp. eaaw6275 ◽

Cited By ~ 24

Author(s):

Mary E. Prendergast ◽

Mark Lipson ◽

Elizabeth A. Sawchuk ◽

Iñigo Olalde ◽

Christine A. Ogola ◽

...

Keyword(s):

Iron Age ◽

Food Production ◽

Sub Saharan Africa ◽

Eastern Africa ◽

Multiphase Model ◽

Later Stone Age ◽

Genome Wide ◽

Genome Wide Data ◽

Sub Saharan ◽

Pastoral Neolithic

How food production first entered eastern Africa ~5000 years ago and the extent to which people moved with livestock is unclear. We present genome-wide data from 41 individuals associated with Later Stone Age, Pastoral Neolithic (PN), and Iron Age contexts in what are now Kenya and Tanzania to examine the genetic impacts of the spreads of herding and farming. Our results support a multiphase model in which admixture between northeastern African–related peoples and eastern African foragers formed multiple pastoralist groups, including a genetically homogeneous PN cluster. Additional admixture with northeastern and western African–related groups occurred by the Iron Age. These findings support several movements of food producers while rejecting models of minimal admixture with foragers and of genetic differentiation between makers of distinct PN artifacts.

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Admixture into and within sub-Saharan Africa

eLife ◽

10.7554/elife.15266 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 57

Author(s):

George BJ Busby ◽

Gavin Band ◽

Quang Si Le ◽

Muminatou Jallow ◽

Edith Bougama ◽

...

Keyword(s):

Gene Flow ◽

Geographic Region ◽

Sub Saharan Africa ◽

Genome Wide ◽

A Genome ◽

Depth Analysis ◽

Shared Ancestry ◽

Sub Saharan ◽

Linguistic Groups ◽

Insight Into

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology.

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Ancient genomes reveal complex patterns of population movement, interaction, and replacement in sub-Saharan Africa

Science Advances ◽

10.1126/sciadv.aaz0183 ◽

2020 ◽

Vol 6 (24) ◽

pp. eaaz0183 ◽

Cited By ~ 2

Author(s):

Ke Wang ◽

Steven Goldstein ◽

Madeleine Bleasdale ◽

Bernard Clist ◽

Koen Bostoen ◽

...

Keyword(s):

Southern Africa ◽

Sub Saharan Africa ◽

The Past ◽

Genome Wide ◽

Movement Interaction ◽

Genome Wide Data ◽

Sub Saharan ◽

Population Interactions ◽

Eastern And Southern Africa ◽

Complex Trajectories

Africa hosts the greatest human genetic diversity globally, but legacies of ancient population interactions and dispersals across the continent remain understudied. Here, we report genome-wide data from 20 ancient sub-Saharan African individuals, including the first reported ancient DNA from the DRC, Uganda, and Botswana. These data demonstrate the contraction of diverse, once contiguous hunter-gatherer populations, and suggest the resistance to interaction with incoming pastoralists of delayed-return foragers in aquatic environments. We refine models for the spread of food producers into eastern and southern Africa, demonstrating more complex trajectories of admixture than previously suggested. In Botswana, we show that Bantu ancestry post-dates admixture between pastoralists and foragers, suggesting an earlier spread of pastoralism than farming to southern Africa. Our findings demonstrate how processes of migration and admixture have markedly reshaped the genetic map of sub-Saharan Africa in the past few millennia and highlight the utility of combined archaeological and archaeogenetic approaches.

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The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa

Pharmacogenetics and Genomics ◽

10.1097/fpc.0b013e3283097311 ◽

2008 ◽

Vol 18 (10) ◽

pp. 877-886 ◽

Cited By ~ 26

Author(s):

Krishna R. Veeramah ◽

Mark G. Thomas ◽

Michael E. Weale ◽

David Zeitlyn ◽

Ayele Tarekegn ◽

...

Keyword(s):

High Frequency ◽

Sub Saharan Africa ◽

Functional Variant ◽

Sub Saharan

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A Genome-Wide Association Study Identifies SNP Markers for Virulence in Magnaporthe oryzae Isolates from Sub-Saharan Africa

10.1101/418509 ◽

2018 ◽

Cited By ~ 1

Author(s):

Veena Devi Ganeshan ◽

Stephen O. Opiyo ◽

Samuel K. Mutiga ◽

Felix Rotich ◽

David M. Thuranira ◽

...

Keyword(s):

Association Study ◽

Magnaporthe Oryzae ◽

Genome Wide Association Study ◽

Significant Snps ◽

Sub Saharan Africa ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome ◽

Sub Saharan ◽

Genomic Regions

ABSTRACTThe fungal phytopathogen Magnaporthe oryzae causes blast disease in cereals such as rice and finger millet worldwide. In this study, we assessed genetic diversity of 160 isolates from nine sub-Saharan Africa (SSA) and other principal rice producing countries and conducted a genome-wide association study (GWAS) to identify the genomic regions associated with virulence of M. oryzae. GBS of isolates provided a large and high-quality 617K single nucleotide polymorphism (SNP) dataset. Disease ratings for each isolate was obtained by inoculating them onto differential lines and locally-adapted rice cultivars. Genome-wide association studies were conducted using the GBS dataset and sixteen disease rating datasets. Principal Component Analysis (PCA) was used an alternative to population structure analysis for studying population stratification from genotypic data. A significant association between disease phenotype and 528 SNPs was observed in six GWA analyses. Homology of sequences encompassing the significant SNPs was determined to predict gene identities and functions. Seventeen genes recurred in six GWA analyses, suggesting a strong association with virulence. Here, the putative genes/genomic regions associated with the significant SNPs are presented.

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Recovering signals of ghost archaic introgression in African populations

10.1101/285734 ◽

2018 ◽

Cited By ~ 13

Author(s):

Arun Durvasula ◽

Sriram Sankararaman

Keyword(s):

High Frequency ◽

Substantial Contribution ◽

Genome Sequences ◽

Modern Humans ◽

Frequency Spectra ◽

Adaptive Introgression ◽

Genome Wide ◽

African Populations ◽

Archaic Introgression ◽

Sub Saharan

AbstractWhile introgression from Neanderthals and Denisovans has been well-documented in modern humans outside Africa, the contribution of archaic hominins to the genetic variation of present-day Africans remains poorly understood. Using 405 whole-genome sequences from four sub-Saharan African populations, we provide complementary lines of evidence for archaic introgression into these populations. Our analyses of site frequency spectra indicate that these populations derive 2-19% of their genetic ancestry from an archaic population that diverged prior to the split of Neanderthals and modern humans. Using a method that can identify segments of archaic ancestry without the need for reference archaic genomes, we built genome-wide maps of archaic ancestry in the Yoruba and the Mende populations that recover about 482 and 502 megabases of archaic sequence, respectively. Analyses of these maps reveal segments of archaic ancestry at high frequency in these populations that represent potential targets of adaptive introgression. Our results reveal the substantial contribution of archaic ancestry in shaping the gene pool of present-day African populations.One sentence summaryMultiple present-day African populations inherited genes from an unknown archaic population that diverged before modern humans and Neanderthals split.

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Interaction between M. tuberculosis Lineage and Human Genetic Variants Reveals Novel Pathway Associations with Severity of TB

Pathogens ◽

10.3390/pathogens10111487 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1487

Author(s):

Michael L. McHenry ◽

Eddie M. Wampande ◽

Moses L. Joloba ◽

LaShaunda L. Malone ◽

Harriet Mayanja-Kizza ◽

...

Keyword(s):

Genetic Variation ◽

Clinical Presentation ◽

Sub Saharan Africa ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Human Genomes ◽

Genome Wide ◽

Sub Saharan ◽

Cellular Replication

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulates disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified three MTBC lineages, of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single-nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (n = 149 and n = 127). We found a significant interaction between an SNP in PPIAP2 and the Uganda lineage (combined p = 4 × 10−8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host–pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human–MTBC coevolution is likely to explain patterns of disease severity.

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Presence of additional P. vivax malaria in Duffy negative individuals from Southwestern Nigeria: Short Report

10.21203/rs.3.rs-15945/v1 ◽

2020 ◽

Author(s):

MARY Aigbiremo OBOH ◽

Upasana Shyamsunder Singh ◽

Daouda Ndiaye ◽

Aida Sadikh Badiane ◽

Nazia Anwar Ali ◽

...

Keyword(s):

Vivax Malaria ◽

National Level ◽

Sub Saharan Africa ◽

Diagnostic Tools ◽

Short Report ◽

Southwestern Nigeria ◽

Malaria Epidemiology ◽

High Prevalence ◽

Sub Saharan ◽

Duffy Negative

Abstract Background Malaria in sub-Saharan Africa (sSA) is thought to be hugely caused by Plasmodium falciparum . Recently, growing reports of cases due to P. ovale , P. malariae , and P. vivax have been significantly reported to play a role in malaria epidemiology in sSA. This in fact is due to the usage of very sensitive diagnostic tools (e.g. PCR) which have highlighted the underestimation of non-falciparum malaria in this sub-region. P. vivax was historically thought to be absent in sSA due to the high prevalence of the Duffy null antigen in individuals residing in this sub-continent. For example, recent studies reporting the detection of vivax malaria in Duffy-negative individuals from Mali, Mauritania, Cameroon to mention a few challenges this notion.Methods Following our earlier report of P. vivax in Duffy-negative individuals, we have collected and assessed RDT and/or microscope malaria positive samples following the conventional PCR method and DNA sequencing to confirm both single/mixed infections as well as the Duffy status of the individuals.Results Amplification of Plasmodium gDNA was possible in 59.9% (145/242) of the evaluated isolates and as expected P. falciparum was the most predominant (91.7%) species identified. Interestingly, four P. vivax isolates were identified either as single (3) or mixed (1 – P. falciparum / P. vivax ) infection. Sequencing results confirmed, all vivax isolates as truly vivax malaria and their Duffy status to be that of the Duffy-negative genotype.Conclusion Identification of more vivax isolates among these Duffy-negative individuals from Nigeria, substantiate the expanding body of evidence on the ability of P. vivax to infect RBCs that do not express the DARC gene. Hence, such genetic-epidemiological study should be conducted at the national level in order to evaluate the actual burden of P. vivax in the country.

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