Fine-scale Genetic Structure Research Articles

Using intraspecific molecular and phenotypic variation to promote multi-functionality of reforestation during climate change – A review of tropical forest case studies in South-east Asia

Abstract The study of intraspecific genetic variation in plant traits for use in tropical forest restoration has broad potential for increasing our ability to achieve multi-functional objectives during this era of climate change. Developing seed-sourcing guidelines that optimize phenotypic characteristics best suited to a particular planting site as well as to future conditions imposed by environmental change could be useful for effective reforestation. Because evolution operates differently across tree species, this is an especially cumbersome task in tropical forests that contain thousands of species. Partially due to this high plant diversity, research and application of intraspecific variation in genetics, plant traits, and plant function in tropical forests wane far behind less diverse forest biomes. To examine the potential for improving reforestation efforts in tropical forests by considering intraspecific variation in plant traits and functions, we review the state of knowledge on intraspecific variation in South-east Asia as a case study. We focus on the dipterocarp family ( Dipterocarpaceae ), a highly diverse family of 16 genera with approximately 695 known species that often dominate lowland tropical rainforests of South-east Asia with many of these forests in a degraded state and in need of restoration. We found that there is research accumulating to understand genetic variation in approximately 10% of these 695 species. Intraspecific molecular variation exists at different spatial scales among species with 74% of species having moderate to high population differentiation (Fst > 0.10) and 92% of species with evidence of fine-scale genetic structure. Although this suggests a high potential for trait variation, few studies associated molecular with phenotypic variation. Seventeen tree species across 11 studies revealed intraspecific variation in traits or functions. Research indicates that intraspecific variation in growth may vary two-fold and drought tolerance four-fold among genotypes highlighting the possibility to pre-adapt trees to climate change during reforestation and to use intraspecific variation to promote the use of native species in commercial forestry. Our review presents opportunities and ideas for developing seed-sourcing guidelines to take advantage of intraspecific variation in traits and function by identifying how to locate this variation, which species would benefit, and how to test for trait variation. We also highlight an emerging area of research on local adaptation, common garden studies, and adaptive drought conditioning to improve reforestation during climate change.

Fine-scale spatial genetic structure and dispersal among Italian smooth newt populations in a rural landscape

Amphibians are particularly sensitive to habitat loss and fragmentation caused by the intensification and modernization of farming occurring in the second half of the twentieth century in the Mediterranean basin. However, artificial water bodies, associated with traditional husbandry, proved to be important surrogate for amphibian feeding and reproduction. Here, multilocus genotypes were used to investigate the spatial population structure of Lissotriton vulgaris meridionalis and the role of drinking troughs in supporting viable breeding populations within a rural landscape interested by traditional husbandry and agriculture. Our genetic analysis highlighted the conservation value and the potential stepping-stone function of artificial aquatic sites in the dispersal of the species and for the gene flow maintenance. Indeed, populations of drinking troughs show allelic richness and heterozygosity levels comparable to those from natural ponds and there is no great evidence of genetic bottlenecks. A complex system of artificial aquatic sites and few natural wetlands was identified sustaining a well-structured network of demes highly interconnected with themselves and natural aquatic sites. The conservation of the identified genetic clusters may be useful to prevent further population declines and future loss of genetic diversity within the study area characterized by scarce natural wetlands that frequently dried because of agricultural practices and strong seasonality. Site-specific protection measures are needed to contrast the progressive disappearance of drinking troughs observed in the last years in Italy because of the abandonment of traditional farming practices in favour of modern agriculture and intensive farming.

Fine-scale genetic structure in rhizosphere microbial communities associated with Chamaecrista fasciculata (Fabaceae).

Soil microbiota of the rhizosphere are an important extension of the plant phenotype because they impact the health and fitness of host plants. The composition of these communities is expected to differ among host plants due to influence by host genotype. Given that many plant populations exhibit fine-scale genetic structure (SGS), associated microbial communities may also exhibit SGS. In this study, we tested this hypothesis using Chamaecrista fasciculata, a legume species that has previously been determined to have significant SGS. We collected genetic data from prokaryotic and fungal rhizosphere communities in association with 70 plants in an area of ~400 square meters to investigate the presence of SGS in microbial communities. Bacteria of Acidobacteria, Protobacteria, and Bacteroidetes and fungi of Basidiomycota, Ascomycota, and Mortierellomycota were dominant members of the rhizosphere. Although microbial alpha diversity did not differ significantly among plants hosts, we detected significant compositional differences among the microbial communities as well as isolation by distance. The strongest factor associated with microbial distance was genetic distance of the other microbial community, followed by geographic distance, but there was not a significant association with plant genetic distance for either microbial community. This study further demonstrates the strong potential for spatial structuring of soil microbial communities at the smallest spatial scales and provides further insight into the complexity of factors that influence microbial composition in soils and in association with host plants.

Fine-scale genetic structure of co-occurring seagrass species highlights the importance of repeated seedling recruitment (Leyte Island, Philippines)

Seagrasses are recognized for their fundamental and ecological functions in coastal environments. Movement ecology and dispersal mechanism of organisms are hypothesized to have a profound significance for the dynamics and resilience of populations and ecosystems. We tested this hypothesis by comparing the genetic diversity and fine-scaled structure of co-occurring seagrass populations of Thalassia hemprichii and Cymodocea serrulata, which differ in their survival strategy and movement ecology. Two hundred eighty-four and two hundred sixty-three individuals of T. hemprichii and C. serrulata from 6 seagrass meadows along Leyte, Philippines were genotyped using 15 and 9 microsatellite markers, respectively. Thalassia hemprichii was observed to have higher genotypic diversity, while clonal elongation was more pronounced for C. serrulata. Repeated seedling recruitment followed by rhizome elongation was observed as an important strategy of resilience and indicated the complementary importance of both sexual and asexual reproduction of these species. Moreover, fine-scale spatial structure analysis revealed that repeated seed recruitment and pollen flow occurred locally, yielding higher kinship values at very close distances of < 5 m, indicating its importance for the maintenance of genetic diversity. An individual based STRUCTURE analysis showed three putative gene pools for both species. Overall, our findings have important implications for understanding the processes and dynamics of populations before conservation efforts. Depending on the strategy of the species, efforts should focus on preserving natural expansion of existing beds and enabling local seed recruitment for successful conservation.

East‒West genetic differentiation across the Indo-Burma hotspot: evidence from two closely related dioecious figs

BackgroundUnderstanding biodiversity patterns and their underlying mechanisms is of interest to ecologists, biogeographers and conservationists and is critically important for conservation efforts. The Indo-Burma hotspot features high species diversity and endemism, yet it also faces significant threats and biodiversity losses; however, few studies have explored the genetic structure and underlying mechanisms of Indo-Burmese species. Here, we conducted a comparative phylogeographic analysis of two closely related dioecious Ficus species, F. hispida and F. heterostyla, based on wide and intensive population sampling across Indo-Burma ranges, using chloroplast (psbA-trnH, trnS-trnG) and nuclear microsatellite (nSSR) markers, as well as ecological niche modeling.ResultsThe results indicated large numbers of population-specific cpDNA haplotypes and nSSR alleles in the two species. F. hispida showed slightly higher chloroplast diversity but lower nuclear diversity than F. heterostyla. Low-altitude mountainous areas of northern Indo-Burma were revealed to have high genetic diversity and high habitat suitability, suggesting potential climate refugia and conservation priority areas. Strong phylogeographic structure and a marked east‒west differentiation pattern were observed in both species, due to the interactions between biotic and abiotic factors. Interspecific dissimilarities at fine-scale genetic structure and asynchronized historical dynamics of east‒west differentiation between species were also detected, which were attributed to different species-specific traits.ConclusionsWe confirm hypothesized predictions that interactions between biotic and abiotic factors largely determine the patterns of genetic diversity and phylogeographic structure of Indo-Burmese plants. The east‒west genetic differentiation pattern observed in two targeted figs can be generalized to some other Indo-Burmese plants. The results and findings of this work will contribute to the conservation of Indo-Burmese biodiversity and facilitate targeted conservation efforts for different species.

Mitogenomics of the Koryaks and Evens of the northern coast of the Sea of Okhotsk.

Due to the geographical proximity of the northern coast of the Sea of Okhotsk and Kamchatka Peninsula to the Beringia, the indigenous populations of these territories are of great interest for elucidating the human settlement history of northern Asia and America. Meanwhile, there is a clear shortage of genetic studies of the indigenous populations of the northern coast of the Sea of Okhotsk. Here, in order to examine their fine-scale matrilineal genetic structure, ancestry and relationships with neighboring populations, we analyzed 203 complete mitogenomes (174 of which are new) from population samples of the Koryaks and Evens of the northern coast of the Sea of Okhotsk and the Chukchi of the extreme northeast Asia. The patterns observed underscore the reduced level of genetic diversity found in the Koryak, Even, and Chukchi populations, which, along with the high degree of interpopulation differentiation, may be the result of genetic drift. Our phylogeographic analysis reveals common Paleo-Asiatic ancestry for 51.1% of the Koryaks and 17.8% of the Evens. About third of the mitogenomes found in the Koryaks and Evens might be considered as ethno-specific, as these are virtually absent elsewhere in North, Central and East Asia. Coalescence ages of most of these lineages coincide well with the emergence and development of the Tokarev and Old Koryak archaeological cultures associated with the formation of the Koryaks, as well as with the period of separation and split of the North Tungusic groups migrated northwards from the Lake Baikal or the Amur River area.

Correction: Genetic diversity and fine-scale spatial genetic structure of unmanaged old-growth versus managed second-growth populations of Scots pine (Pinus sylvestris L.) in Lithuania

Correction: Genetic diversity and fine-scale spatial genetic structure of unmanaged old-growth versus managed second-growth populations of Scots pine (Pinus sylvestris L.) in Lithuania

Fine-scale genetic structure of Magnolia iltisiana in forest regeneration sites with a history of selective logging

Background: Selective logging is a frequent practice in the Tropical Montane Cloud Forest which can impact forest regeneration and the genetic makeup of successive generations of trees. The spatial clustering of genetically related individuals, fine-scale genetic structure (FSGS), can develop from the reduction of gene dispersal and the decrease in the number of reproductive individuals at the local scale due to selective logging.&#x0D; Questions: In regeneration sites with a history of selective logging, does FSGS differ from a site without such a history? Is FSGS stronger in seedlings and saplings relative to juveniles and adults? Is genetic diversity similar among life stages and sites?&#x0D; Studied species: Magnolia iltisiana an endemic tree.&#x0D; Study site and dates: Sierra de Manantlan Biosphere Reserve, Jalisco, Mexico.&#x0D; 2020.&#x0D; Methods: We evaluated genetic diversity, genetic structure, and FSGS across four life stages (seedlings, saplings, juveniles, and adults) by genotyping 211 individuals with seven nuclear microsatellite loci in two regeneration and one conserved site.&#x0D; Results: We found statistically significant FSGS in the two regeneration sites only for seedlings and saplings, while no evidence of FSGS was detected in the conserved site. No differences in genetic diversity estimates and structure were found among life stages.&#x0D; Conclusions: Our study does not suggest an effect of selective logging on genetic diversity on the contrasted conditions and an FSGS pattern only in the earlier stages of the regeneration sites in M. iltisiana.

Do habitat fragmentation and degradation influence the strength of fine-scale spatial genetic structure in plants? A global meta-analysis.

As primarily sessile organisms, plants often show a non-random spatial distribution of genotypes over distance. This process known as fine-scale spatial genetic structure (FSGS) has been suggested through systematic reviews to depend on life form, mating system, and pollen and seed dispersal vectors, while there is no consensus on its behaviour due to external factors, such as anthropogenic habitat changes. By conducting a systematic review and global meta-analysis of empirical FSGS studies, we aimed to evaluate how anthropogenic habitat fragmentation and degradation influence the strength of FSGS in plant populations by means of the Sp statistic. Moreover, we tested how pollination and seed dispersal vectors contribute to the variation of the Sp statistic. We retrieved 243 FSGS studies from 1960 to 2020 of which only 65 were informative for the systematic review. Most empirical studies comprised outcrossers (84%) and trees (67%), with few herbs (23%) and scarce annual species (2%). In weighted meta-analyses for 116 plant populations (31 studies), we did not detect significant effects in the magnitude of effect sizes for the Sp statistic among undisturbed, degraded and fragmented habitats. Results showed significant effects for seed dispersal vectors, but not for pollination. Overall, we observed high variation among the effect sizes (not related to the goodness-of-fit of mixed models) of habitat status, pollination and seed dispersal categories, which precludes identifying biological trends on the Sp statistic. More empirical studies are needed that contrast multiple plant populations in disturbed versus undisturbed habitats, and by increasing the taxonomic groups, such as herbs and annual plants.

Biogeographic provinces and genomically delineated stocks are congruent in snapper (Chrysophrys auratus) from southeastern Australia

AbstractMarine species often exhibit genetic discontinuities concordant with biogeographic boundaries, frequently occurring due to changes in ocean circulation, bathymetry, coastline topography, and temperature. Here, we used 10 916 single nucleotide polymorphisms (SNPs) to assess the concordance between population genomic differentiation and coastal biogeography in the fishery-important snapper (Chrysophrys auratus) across southeastern Australia. Additionally, we investigated whether spatial scales of assessment and management of snapper align with evidence from population genomics. We detected genomic structure concordant with the region's three biogeographic provinces across snapper from 11 localities (n = 488) between the west coast of South Australia and the south coast of New South Wales. We also detected fine-scale genetic structuring relating to spatial variation in spawning and recruitment dynamics, as well as temporal stability in the genomic signal associated with two important spawning areas. The current management boundaries in the region coincided with either the genetic breaks at bioregional boundaries or with local-scale variation. Our study highlights the value of population genomic surveys in species with high dispersal potential for uncovering stock boundaries and demographic variation related to spawning and recruitment. It also illustrates the importance of marine biogeography in shaping population structure in commercial species with high dispersal potential.

The Newfoundland and Labrador mosaic founder population descends from an Irish and British diaspora from 300 years ago

The founder population of Newfoundland and Labrador (NL) is a unique genetic resource, in part due to its geographic and cultural isolation, where historical records describe a migration of European settlers, primarily from Ireland and England, to NL in the 18th and 19th centuries. Whilst its historical isolation, and increased prevalence of certain monogenic disorders are well appreciated, details of the fine-scale genetic structure and ancestry of the population are lacking. Understanding the genetic origins and background of functional, disease causing, genetic variants would aid genetic mapping efforts in the Province. Here, we leverage dense genome-wide SNP data on 1,807 NL individuals to reveal fine-scale genetic structure in NL that is clustered around coastal communities and correlated with Christian denomination. We show that the majority of NL European ancestry can be traced back to the south-east and south-west of Ireland and England, respectively. We date a substantial population size bottleneck approximately 10-15 generations ago in NL, associated with increased haplotype sharing and autozygosity. Our results reveal insights into the population history of NL and demonstrate evidence of a population conducive to further genetic studies and biomarker discovery.

Population genetic structure of the maize weevil, Sitophilus zeamais, in southern Mexico.

The maize weevil, Sitophilus zeamais, is a ubiquitous pest of maize and other cereal crops worldwide and remains a threat to food security in subsistence communities. Few population genetic studies have been conducted on the maize weevil, but those that exist have shown that there is very little genetic differentiation between geographically dispersed populations and that it is likely the species has experienced a recent range expansion within the last few hundred years. While the previous studies found little genetic structure, they relied primarily on mitochondrial and nuclear microsatellite markers for their analyses. It is possible that more fine-scaled population genetic structure exists due to local adaptation, the biological limits of natural species dispersal, and the isolated nature of subsistence farming communities. In contrast to previous studies, here, we utilized genome-wide single nucleotide polymorphism data to evaluate the genetic population structure of the maize weevil from the southern and coastal Mexican states of Oaxaca and Chiapas. We employed strict SNP filtering to manage large next generation sequencing lane effects and this study is the first to find fine-scale genetic population structure in the maize weevil. Here, we show that although there continues to be gene flow between populations of maize weevil, that fine-scale genetic structure exists. It is possible that this structure is shaped by local adaptation of the insects, the movement and trade of maize by humans in the region, geographic barriers to gene flow, or a combination of these factors.

Population structure and genome-wide evolutionary signatures reveal putative climate-driven habitat change and local adaptation in the large yellow croaker

The large yellow croaker (Larimichthyscrocea) is one of the most economically valuable marine fish in China and is a notable species in ecological studies owing to a serious collapse of wild germplasm in the past few decades. The stock division and species distribution, which have important implications for ecological protection, germplasm recovery, and fishery resource management, have been debated since the 1960s. However, it is still uncertain even how many stocks exist in this species. To address this, we evaluated the fine-scale genetic structure of large yellow croaker populations distributed along the eastern and southern Chinese coastline based on 7.64 million SNP markers. Compared with the widely accepted stock boundaries proposed in the 1960s, our results revealed that a climate-driven habitat change probably occurred between the Naozhou (Nanhai) Stock and the Ming-Yuedong (Mindong) Stock. The boundary between these two stocks might have shifted northwards from the Pearl River Estuary to the northern area of the Taiwan Strait, accompanied by highly asymmetric introgression. In addition, we found divergent landscapes of natural selection between the stocks inhabiting northern and southern areas. The northern population exhibited highly agminated signatures of strong natural selection in genes related to developmental processes, whereas moderate and interspersed selective signatures were detected in many immune-related genes in the southern populations. These findings establish the stock status and genome-wide evolutionary landscapes of large yellow croaker, providing a basis for conservation, fisheries management and further evolutionary biology studies.

Fine-Scale Spatial Genetic Structure of Remnant Populations of Abies religiosa, in a Temperate Forest in Central Mexico

Genetic structure of a population can be molded by the resistance of the landscape or the distance between populations that function as barriers to gene flow. We analyzed the population genetic structure of Abies religiosa on a fine spatial scale and examined isolation models by resistance and distance. We collected vegetative tissue from populations located at the altitudinal extremes of the distribution range of the species on three slopes of La Malinche National Park (LMNP) (South, North, and East) in central Mexico. Genomic DNA was obtained using the CTAB 2X method, and eight microsatellite chloroplast loci were amplified. The genetic structure was identified based on an Analysis of Molecular Variance, a Discriminant Analysis of Principal Components with cross-validation and a spatial Principal Component Analysis using the Gabriel-type connectivity network. The isolation hypotheses were evaluated by constructing partial Mantel tests using Reciprocal Causal Modeling and Maximum Likelihood Population Effects models. A genetic structure of isolation by resistance to elevation was identified, and two genetic groups were recognized: one including populations of the South slope and the other comprising populations of the North and East slopes. We detected in Abies religiosa populations of the LMNP an isolation by resistance to elevation that determines the genetic structure, and the greatest genetic exchange between groups of populations located at higher altitudes. It is suggested to promote the connectivity between slopes through assisted migration and immediately halt land-use changes, as part of the actions to preserve genetic diversity in the LMPN. This study contributes to the knowledge of the spatial genetic structure of species at risk in the Mexican temperate forest for their conservation.

Dense sampling of ethnic groups within African countries reveals fine-scale genetic structure and extensive historical admixture.

Previous studies have highlighted how African genomes have been shaped by a complex series of historical events. Despite this, genome-wide data have only been obtained from a small proportion of present-day ethnolinguistic groups. By analyzing new autosomal genetic variation data of 1333 individuals from over 150 ethnic groups from Cameroon, Republic of the Congo, Ghana, Nigeria, and Sudan, we demonstrate a previously underappreciated fine-scale level of genetic structure within these countries, for example, correlating with historical polities in western Cameroon. By comparing genetic variation patterns among populations, we infer that many northern Cameroonian and Sudanese groups share genetic links with multiple geographically disparate populations, likely resulting from long-distance migrations. In Ghana and Nigeria, we infer signatures of intermixing dated to over 2000 years ago, corresponding to reports of environmental transformations possibly related to climate change. We also infer recent intermixing signals in multiple African populations, including Congolese, that likely relate to the expansions of Bantu language-speaking peoples.

Genetic diversity and fine-scale spatial genetic structure of unmanaged old-growth versus managed second-growth populations of Scots pine (Pinus sylvestris L.) in Lithuania

Genetic diversity and fine-scale spatial genetic structure of unmanaged old-growth versus managed second-growth populations of Scots pine (Pinus sylvestris L.) in Lithuania

High-Throughput Microsatellite Markers Development for Genetic Characterization of Emerging Sporothrix Species.

Sporotrichosis is the main subcutaneous mycosis worldwide transmitted by animal or plant vectors and often escalates to outbreaks or epidemics. The current cat-transmitted sporotrichosis driven by Sporothrix brasiliensis has become a significant public health issue in South America. Transmission dynamics remain enigmatic due to the lack of development of polymorphic markers for molecular epidemiological analysis. This study used a high-throughput mining strategy to characterize simple sequence repeat (SSR) markers from Sporothrix genomes. A total of 118,140-143,912 SSR loci were identified (82,841-98,369 unique markers), with a 3651.55-3804.65 SSR/Mb density and a majority of dinucleotides motifs (GC/CG). We developed a panel of 15 highly polymorphic SSR markers suitable for genotyping S. brasiliensis, S. schenckii, and S. globosa. PCR amplification revealed 240 alleles in 180 Sporothrix isolates with excellent polymorphic information content (PIC = 0.9101), expected heterozygosity (H = 0.9159), and discriminating power (D = 0.7127), supporting the effectiveness of SSR markers in uncovering cryptic genetic diversity. A systematic population genetic study estimated three clusters, corresponding to S. brasiliensis (population 1, n = 97), S. schenckii (population 2, n = 49), and S. globosa (population 3, n = 34), with a weak signature of mixed ancestry between populations 1 and 2 or 3 and 2. Partitioning of genetic variation via AMOVA revealed highly structured populations (ΦPT = 0.539; Nm = 0.213; p < 0.0001), with approximately equivalent genetic variability within (46%) and between (54%) populations. Analysis of SSR diversity supports Rio de Janeiro (RJ) as the center of origin for contemporary S. brasiliensis infections. The recent emergence of cat-transmitted sporotrichosis in northeastern Brazil indicates an RJ-Northeast migration resulting in founder effects during the introduction of diseased animals into sporotrichosis-free areas. Our results demonstrated high cross-species transferability, reproducibility, and informativeness of SSR genetic markers, helping dissect deep and fine-scale genetic structures and guiding decision making to mitigate the harmful effects of the expansion of cat-transmitted sporotrichosis.

Molecular identification and mapping of mixed root samples to species and individuals.

This article is a Commentary on Osborne et al. (2023), 238: 1305–1317.

The Low Variability of Tc24 in Trypanosoma cruzi TcI as an Advantage for Chagas Disease Prophylaxis and Diagnosis in Mexico.

(1) Background: Chagas disease is the main neglected tropical disease in America. It is estimated that around 6 million people are currently infected with the parasite in Latin America, and 25 million live in endemic areas with active transmission. The disease causes an estimated economic loss of USD 24 billion dollars annually, with a loss of 75,200 working years per year of life; it is responsible for around ~12,000 deaths annually. Although Mexico is an endemic country that recorded 10,186 new cases of Chagas disease during the period of 1990-2017, few studies have evaluated the genetic diversity of genes that could be involved in the prophylaxis and/or diagnosis of the parasite. One of the possible candidates proposed as a vaccine target is the 24 kDa trypomastigote excretory-secretory protein, Tc24, whose protection is linked to the stimulation of T. cruzi-specific CD8+ immune responses. (2) Methods: The aim of the present study was to evaluate the fine-scale genetic diversity and structure of Tc24 in T. cruzi isolates from Mexico, and to compare them with other populations reported in the Americas with the aim to reconsider the potential role of Tc24 as a key candidate for the prophylaxis and improvement of the diagnosis of Chagas disease in Mexico. (3) Results: Of the 25 Mexican isolates analysed, 48% (12) were recovered from humans and 24% (6) recovered from Triatoma barberi and Triatoma dimidiata. Phylogenetic inferences revealed a polytomy in the T. cruzi clade with two defined subgroups, one formed by all sequences of the DTU I and the other formed by DTU II-VI; both subgroups had high branch support. Genetic population analysis detected a single (monomorphic) haplotype of TcI throughout the entire distribution across both Mexico and South America. This information was supported by Nei's pairwise distances, where the sequences of TcI showed no genetic differences. (4) Conclusions: Given that both previous studies and the findings of the present work confirmed that TcI is the only genotype detected from human isolates obtained from various states of Mexico, and that there is no significant genetic variability in any of them, it is possible to propose the development of in silico strategies for the production of antigens that optimise the diagnosis of Chagas disease, such as quantitative ELISA methods that use this region of Tc24.

Genome-wide association study identifies novel candidate malaria resistance genes in Cameroon.

Recent data suggest that only a small fraction of severe malaria heritability is explained by the totality of genetic markers discovered so far. The extensive genetic diversity within African populations means that significant associations are likely to be found in Africa. In their series of multi-site genome-wide association studies (GWAS) across sub-Saharan Africa, the Malaria Genomic Epidemiology Network (MalariaGEN) observed specific limitations and encouraged country-specific analyses. Here, we present findings of a GWAS of Cameroonian participants that contributed to MalariaGEN projects (n = 1103). We identified protective associations at polymorphisms within the enhancer region of CHST15 [Benjamin-Hochberg false discovery rate (FDR) < 0.02] that are specific to populations of African ancestry, and that tag strong eQTLs of CHST15 in hepatic cells. In-silico functional analysis revealed a signature of epigenetic regulation of CHST15 that is preserved in populations in historically malaria endemic regions, with haplotype analysis revealing a haplotype that is specific to these populations. Association analysis by ethnolinguistic group identified protective associations within SOD2 (FDR < 0.04), a gene previously shown to be significantly induced in pre-asymptomatic malaria patients from Cameroon. Haplotype analysis revealed substantial heterogeneity within the beta-like globin (HBB) gene cluster amongst the major ethnic groups in Cameroon confirming differential malaria pressure and underscoring age-old fine-scale genetic structure within the country. Our findings revealed novel insights in the evolutionary genetics of populations living in Cameroon under malaria pressure with new significant protective loci (CHST15 and SOD2) and emphasized the significant attenuation of genetic association signals by fine-scale genetic structure.