Strong Signatures Of Selection Research Articles

Trends of genetic changes uncovered by Env- and Eigen-GWAS in wheat and barley

Key messageVariety age and population structure detect novel QTL for yield and adaptation in wheat and barley without the need to phenotype.The process of crop breeding over the last century has delivered new varieties with increased genetic gains, resulting in higher crop performance and yield. However, in many cases, the alleles and genomic regions underpinning this success remain unknown. This is partly due to the difficulty of generating sufficient phenotypic data on large numbers of historical varieties to enable such analyses. Here we demonstrate the ability to circumvent such bottlenecks by identifying genomic regions selected over 100 years of crop breeding using age of a variety as a surrogate for yield. Rather than collecting phenotype data, we deployed ‘environmental genome-wide association scans’ (EnvGWAS) based on variety age in two of the world’s most important crops, wheat and barley, and detected strong signals of selection across both genomes. EnvGWAS identified 16 genomic regions in barley and 10 in wheat with contrasting patterns between spring and winter types of the two crops. To further examine changes in genome structure, we used the genomic relationship matrix of the genotypic data to derive eigenvectors for analysis in EigenGWAS. This detected seven major chromosomal introgressions that contributed to adaptation in wheat. EigenGWAS and EnvGWAS based on variety age avoid costly phenotyping and facilitate the identification of genomic tracts that have been under selection during breeding. Our results demonstrate the potential of using historical cultivar collections coupled with genomic data to identify chromosomal regions under selection and may help guide future plant breeding strategies to maximise the rate of genetic gain and adaptation.

A selection pressure landscape for 870 human polygenic traits.

Characterizing the natural selection of complex traits is important for understanding human evolution and both biological and pathological mechanisms. We leveraged genome-wide summary statistics for 870 polygenic traits and attempted to quantify signals of selection on traits of different forms in European ancestry across four periods in human history and evolution. We found that 88% of these traits underwent polygenic change in the past 2,000-3,000 years. Recent selection was associated with ancient selection signals in the same trait. Traits related to pigmentation, body measurement and nutritional intake exhibited strong selection signals across different time scales. Our findings are limited by our use of exclusively European data and the use of genome-wide association study data, which identify associations between genetic variants and phenotypes that may not be causal. In sum, we provide an overview of signals of selection on human polygenic traits and their characteristics across human evolution, based on a European subset of human genetic diversity. These findings could serve as a foundation for further populational and medical genetic studies.

Genome of the estuarine oyster provides insights into climate impact and adaptive plasticity

Understanding the roles of genetic divergence and phenotypic plasticity in adaptation is central to evolutionary biology and important for assessing adaptive potential of species under climate change. Analysis of a chromosome-level assembly and resequencing of individuals across wide latitude distribution in the estuarine oyster (Crassostrea ariakensis) revealed unexpectedly low genomic diversity and population structures shaped by historical glaciation, geological events and oceanographic forces. Strong selection signals were detected in genes responding to temperature and salinity stress, especially of the expanded solute carrier families, highlighting the importance of gene expansion in environmental adaptation. Genes exhibiting high plasticity showed strong selection in upstream regulatory regions that modulate transcription, indicating selection favoring plasticity. Our findings suggest that genomic variation and population structure in marine bivalves are heavily influenced by climate history and physical forces, and gene expansion and selection may enhance phenotypic plasticity that is critical for the adaptation to rapidly changing environments.

Genomic signatures of domestication and adaptation during geographical expansions of rice cultivation

Rice (Oryza sativa L.), a global staple food now grown on all inhabited continents, was domesticated from its wild progenitor, O. rufipogon Griff., in tropical and subtropical regions of Asia (Oka, 1988). After domestication, the expansions of rice landraces into the present-day range required a diverse array of adaptations to local environments, which included changes in daylight sensitivity, expanded thermal tolerance (for excess cold and heat), adaptations to water availability (drought and waterlogging), and resistance to biotic stresses (Garris et al., 2005; Glaszmann, 1987).

Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region.

The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR–HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR–HLA interactions among all described worldwide populations, and that 83–97% of their KIR–HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR–HLA coevolution and its impact on human health and survival.

Single-genome sequencing reveals within-host evolution of human malaria parasites

Population genomics of bulk malaria infections is unable to examine intrahost evolution; therefore, most work has focused on the role of recombination in generating genetic variation. We used single-cell sequencing protocol for low-parasitaemia infections to generate 406 near-complete single Plasmodium vivax genomes from 11 patients sampled during sequential febrile episodes. Parasite genomes contain hundreds of denovo mutations, showing strong signatures of selection, which are enriched in the ApiAP2 family of transcription factors, known targets of adaptation. Comparing 315 P.falciparum single-cell genomes from 15 patients with our P.vivax data, we find broad complementary patterns of de novo mutation at the gene and pathway level, revealing the importance of within-host evolution during malaria infections.

Evolutionary Profile for (Host and Viral) MLKL Indicates Its Activities as a Battlefront for Extensive Counteradaptation.

Pathogen infection triggers host innate defenses which may result in the activation of regulated cell death (RCD) pathways such as apoptosis. Given a vital role in immunity, apoptotic effectors are often counteracted by pathogen-encoded antagonists. Mounting evidence indicates that programmed necrosis, which is mediated by the RIPK3/MLKL axis and termed necroptosis, evolved as a countermeasure to pathogen-mediated inhibition of apoptosis. Yet, it is unclear whether components of this emerging RCD pathway display signatures associated with pathogen conflict that are rare in combination but common to key host defense factors, namely, rapid evolution, viral homolog (virolog), and cytokine induction. We leveraged evolutionary sequence analysis that examines rates of amino acid replacement, which revealed: 1) strong and recurrent signatures of positive selection for primate and bat RIPK3 and MLKL, and 2) elevated rates of amino acid substitution on multiple RIPK3/MLKL surfaces suggestive of past antagonism with multiple, distinct pathogen-encoded inhibitors. Furthermore, our phylogenomics analysis across poxvirus genomes illuminated volatile patterns of evolution for a recently described MLKL viral homolog. Specifically, poxviral MLKLs have undergone numerous gene replacements mediated by duplication and deletion events. In addition, MLKL protein expression is stimulated by interferons in human and mouse cells. Thus, MLKL displays all three hallmarks of pivotal immune factors of which only a handful of factors like OAS1 exhibit. These data support the hypothesis that over evolutionary time MLKL functions—which may include execution of necroptosis—have served as a major determinant of infection outcomes despite gene loss in some host genomes.

Fine-Scale Genetic Structure and Natural Selection Signatures of Southwestern Hans Inferred From Patterns of Genome-Wide Allele, Haplotype, and Haplogroup Lineages.

The evolutionary and admixture history of Han Chinese have been widely discussed via traditional autosomal and uniparental genetic markers [e.g., short tandem repeats, low-density single nucleotide polymorphisms). However, their fine-scale genetic landscapes (admixture scenarios and natural selection signatures) based on the high-density allele/haplotype sharing patterns have not been deeply characterized. Here, we collected and generated genome-wide data of 50 Han Chinese individuals from four populations in Guizhou Province, one of the most ethnolinguistically diverse regions, and merged it with over 3,000 publicly available modern and ancient Eurasians to describe the genetic origin and population admixture history of Guizhou Hans and their neighbors. PCA and ADMIXTURE results showed that the studied four populations were homogeneous and grouped closely to central East Asians. Genetic homogeneity within Guizhou populations was further confirmed via the observed strong genetic affinity with inland Hmong-Mien people through the observed genetic clade in Fst and outgroup f3/f4-statistics. qpGraph-based phylogenies and f4-based demographic models illuminated that Guizhou Hans were well fitted via the admixture of ancient Yellow River Millet farmers related to Lajia people and southern Yangtze River farmers related to Hanben people. Further ChromoPainter-based chromosome painting profiles and GLOBETROTTER-based admixture signatures confirmed the two best source matches for southwestern Hans, respectively, from northern Shaanxi Hans and southern indigenes with variable mixture proportions in the historical period. Further three-way admixture models revealed larger genetic contributions from coastal southern East Asians into Guizhou Hans compared with the proposed inland ancient source from mainland Southeast Asia. We also identified candidate loci (e.g., MTUS2, NOTCH4, EDAR, ADH1B, and ABCG2) with strong natural selection signatures in Guizhou Hans via iHS, nSL, and ihh, which were associated with the susceptibility of the multiple complex diseases, morphology formation, alcohol and lipid metabolism. Generally, we provided a case and ideal strategy to reconstruct the detailed demographic evolutionary history of Guizhou Hans, which provided new insights into the fine-scale genomic formation of one ethnolinguistically specific targeted population from the comprehensive perspectives of the shared unlinked alleles, linked haplotypes, and paternal and maternal lineages.

Haplotype-resolved genome assembly provides insights into evolutionary history of the tea plant Camellia sinensis

Tea is an important global beverage crop and is largely clonally propagated. Despite previous studies on the species, its genetic and evolutionary history deserves further research. Here, we present a haplotype-resolved assembly of an Oolong tea cultivar, Tieguanyin. Analysis of allele-specific expression suggests a potential mechanism in response to mutation load during long-term clonal propagation. Population genomic analysis using 190 Camellia accessions uncovered independent evolutionary histories and parallel domestication in two widely cultivated varieties, var. sinensis and var. assamica. It also revealed extensive intra- and interspecific introgressions contributing to genetic diversity in modern cultivars. Strong signatures of selection were associated with biosynthetic and metabolic pathways that contribute to flavor characteristics as well as genes likely involved in the Green Revolution in the tea industry. Our results offer genetic and molecular insights into the evolutionary history of Camellia sinensis and provide genomic resources to further facilitate gene editing to enhance desirable traits in tea crops.

Deciphering variation of 239 elite japonica rice genomes for whole genome sequences-enabled breeding

Revealing genomic variation of representative and diverse germplasm is the cornerstone of deploying genomics information into genetic improvement programs of species of agricultural importance. Here we report the re-sequencing of 239 japonica rice elites representing the genetic diversity of japonica germplasm in China, Japan and Korea. A total of 4.8 million SNPs and PAV of 35,634 genes were identified. The elites from Japan and Korea are closely related and relatively less diverse than those from China. A japonica rice pan-genome was constructed, and 35 Mb non-redundant novel sequences were identified, from which 1131 novel genes were predicted. Strong selection signals of genomic regions were detected on most of the chromosomes. The heading date genes Hd1 and Hd3a have been artificially selected during the breeding process. The results from this study lay the foundation for future whole genome sequences-enabled breeding in rice and provide a paradigm for other species.

Ethiopian indigenous goats offer insights into past and recent demographic dynamics and local adaptation in sub-Saharan African goats.

Knowledge on how adaptive evolution and human socio‐cultural and economic interests shaped livestock genomes particularly in sub‐Saharan Africa remains limited. Ethiopia is in a geographic region that has been critical in the history of African agriculture with ancient and diverse human ethnicity and bio‐climatic conditions. Using 52K genome‐wide data analysed in 646 individuals from 13 Ethiopian indigenous goat populations, we observed high levels of genetic variation. Although runs of homozygosity (ROH) were ubiquitous genome‐wide, there were clear differences in patterns of ROH length and abundance and in effective population sizes illustrating differences in genome homozygosity, evolutionary history, and management. Phylogenetic analysis incorporating patterns of genetic differentiation and gene flow with ancestry modelling highlighted past and recent intermixing and possible two deep ancient genetic ancestries that could have been brought by humans with the first introduction of goats in Africa. We observed four strong selection signatures that were specific to Arsi‐Bale and Nubian goats. These signatures overlapped genomic regions with genes associated with morphological, adaptation, reproduction and production traits due possibly to selection under environmental constraints and/or human preferences. The regions also overlapped uncharacterized genes, calling for a comprehensive annotation of the goat genome. Our results provide insights into mechanisms leading to genome variation and differentiation in sub‐Saharan Africa indigenous goats.

Positive selection as a key player for SARS-CoV-2 pathogenicity: Insights into ORF1ab, S and E genes

The human β-coronavirus SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China. It causes Covid-19 disease which has become pandemic. Each of the five-known human β-coronaviruses has four major structural proteins (E, M, N and S) and 16 non-structural proteins encoded by ORF1a and ORF1b together (ORF1ab) that are involved in virus pathogenicity and infectivity. Here, we performed detailed positive selection analyses for those six genes among the four previously known human β-coronaviruses and within 38 SARS-CoV-2 genomes to assess signatures of adaptive evolution using maximum likelihood approaches. Our results suggest that three genes (E, S and ORF1ab genes) are under strong signatures of positive selection among human β-coronavirus, influencing codons that are located in functional important protein domains. The E protein-coding gene showed signatures of positive selection in two sites, Asp 66 and Ser 68, located inside a putative transmembrane α-helical domain C-terminal part, which is preferentially composed by hydrophilic residues. Such Asp and Ser sites substitutions (hydrophilic residues) increase the stability of the transmembrane domain in SARS-CoV-2. Moreover, substitutions in the spike (S) protein S1 N-terminal domain have been found, all of them were located on the S protein surface, suggesting their importance in viral transmissibility and survival. Furthermore, evidence of strong positive selection was detected in three of the SARS-CoV-2 nonstructural proteins (NSP1, NSP3, NSP16), which are encoded by ORF1ab and play vital roles in suppressing host translation machinery, viral replication and transcription and inhibiting the host immune response. These results are insightful to assess the role of positive selection in the SARS-CoV-2 encoded proteins, which will allow to better understand the virulent pathogenicity of the virus and potentially identifying targets for drug or vaccine strategy design

The history and evolution of the Denisovan-EPAS1 haplotype in Tibetans

Recent studies suggest that admixture with archaic hominins played an important role in facilitating biological adaptations to new environments. For example, interbreeding with Denisovans facilitated the adaptation to high-altitude environments on the Tibetan Plateau. Specifically, the EPAS1 gene, a transcription factor that regulates the response to hypoxia, exhibits strong signatures of both positive selection and introgression from Denisovans in Tibetan individuals. Interestingly, despite being geographically closer to the Denisova Cave, East Asian populations do not harbor as much Denisovan ancestry as populations from Melanesia. Recently, two studies have suggested two independent waves of Denisovan admixture into East Asians, one of which is shared with South Asians and Oceanians. Here, we leverage data from EPAS1 in 78 Tibetan individuals to interrogate which of these two introgression events introduced the EPAS1 beneficial sequence into the ancestral population of Tibetans, and we use the distribution of introgressed segment lengths at this locus to infer the timing of the introgression and selection event. We find that the introgression event unique to East Asians most likely introduced the beneficial haplotype into the ancestral population of Tibetans around 48,700 (16,000-59,500) y ago, and selection started around 9,000 (2,500-42,000) y ago. Our estimates suggest that one of the most convincing examples of adaptive introgression is in fact selection acting on standing archaic variation.

Analysis of whole-genome re-sequencing data of ducks reveals a diverse demographic history and extensive gene flow between Southeast/South Asian and Chinese populations

BackgroundThe most prolific duck genetic resource in the world is located in Southeast/South Asia but little is known about the domestication and complex histories of these duck populations.ResultsBased on whole-genome resequencing data of 78 ducks (Anas platyrhynchos) and 31 published whole-genome duck sequences, we detected three geographic distinct genetic groups, including local Chinese, wild, and local Southeast/South Asian populations. We inferred the demographic history of these duck populations with different geographical distributions and found that the Chinese and Southeast/South Asian ducks shared similar demographic features. The Chinese domestic ducks experienced the strongest population bottleneck caused by domestication and the last glacial maximum (LGM) period, whereas the Chinese wild ducks experienced a relatively weak bottleneck caused by domestication only. Furthermore, the bottleneck was more severe in the local Southeast/South Asian populations than in the local Chinese populations, which resulted in a smaller effective population size for the former (7100–11,900). We show that extensive gene flow has occurred between the Southeast/South Asian and Chinese populations, and between the Southeast Asian and South Asian populations. Prolonged gene flow was detected between the Guangxi population from China and its neighboring Southeast/South Asian populations. In addition, based on multiple statistical approaches, we identified a genomic region that included three genes (PNPLA8, THAP5, and DNAJB9) on duck chromosome 1 with a high probability of gene flow between the Guangxi and Southeast/South Asian populations. Finally, we detected strong signatures of selection in genes that are involved in signaling pathways of the nervous system development (e.g., ADCYAP1R1 and PDC) and in genes that are associated with morphological traits such as cell growth (e.g., IGF1R).ConclusionsOur findings provide valuable information for a better understanding of the domestication and demographic history of the duck, and of the gene flow between local duck populations from Southeast/South Asia and China.

R-locus for roaned coat is associated with a tandem duplication in an intronic region of USH2A in dogs and also contributes to Dalmatian spotting.

Structural variations (SVs) represent a large fraction of all genetic diversity, but how this genetic diversity is translated into phenotypic and organismal diversity is unclear. Explosive diversification of dog coat color and patterns after domestication can provide a unique opportunity to explore this question; however, the major obstacle is to efficiently collect a sufficient number of individuals with known phenotypes and genotypes of hundreds of thousands of markers. Using customer-provided information about coat color and patterns of dogs tested on a commercial canine genotyping platform, we identified a genomic region on chromosome 38 that is strongly associated with a mottled coat pattern (roaning) by genome-wide association study. We identified a putative causal variant in this region, an 11-kb tandem duplication (11,131,835-11,143,237) characterized by sequence read coverage and discordant reads of whole-genome sequence data, microarray probe intensity data, and a duplication-specific PCR assay. The tandem duplication is in an intronic region of usherin gene (USH2A), which was perfectly associated with roaning but absent in non-roaned dogs. We detected strong selection signals in this region characterized by reduced nucleotide diversity (π), increased runs of homozygosity, and extended haplotype homozygosity in Wirehaired Pointing Griffons and Australian Cattle Dogs (typically roaned breeds), as well as elevated genetic difference (FST) between Wirehaired Pointing Griffon (roaned) and Labrador Retriever (non-roaned). Surprisingly, all Dalmatians (N = 262) carried the duplication embedded in identical or similar haplotypes with roaned dogs, indicating this region as a shared target of selection during the breed's formation. We propose that the Dalmatian's unique spots were a derived coat pattern by establishing a novel epistatic interaction between roaning "R-locus" on chromosome 38 and an uncharacterized modifier locus. These results highlight the utility of consumer-oriented genotype and phenotype data in the discovery of genomic regions contributing to phenotypic diversity in dogs.

Large genetic diversity and strong positive selection in F-box and GPCR genes among the wild isolates of Caenorhabditis elegans.

The F-box and chemosensory GPCR (csGPCR) gene families are greatly expanded in nematodes, including the model organism Caenorhabditis elegans, compared with insects and vertebrates. However, the intraspecific evolution of these two gene families in nematodes remain unexamined. In this study, we analyzed the genomic sequences of 330 recently sequenced wild isolates of C. elegans using a range of population genetics approaches. We found that F-box and csGPCR genes, especially the Srw family csGPCRs, showed much more diversity than other gene families. Population structure analysis and phylogenetic analysis divided the wild strains into eight non-Hawaiian and three Hawaiian subpopulations. Some Hawaiian strains appeared to be more ancestral than all other strains. F-box and csGPCR genes maintained a great amount of the ancestral variants in the Hawaiian subpopulation and their divergence among the non-Hawaiian subpopulations contributed significantly to population structure. F-box genes are mostly located at the chromosomal arms and high recombination rate correlates with their large polymorphism. Moreover, using both neutrality tests and extended haplotype homozygosity analysis, we identified signatures of strong positive selection in the F-box and csGPCR genes among the wild isolates, especially in the non-Hawaiian population. Accumulation of high-frequency-derived alleles in these genes was found in non-Hawaiian population, leading to divergence from the ancestral genotype. In summary, we found that F-box and csGPCR genes harbor a large pool of natural variants, which may be subjected to positive selection. These variants are mostly mapped to the substrate-recognition domains of F-box proteins and the extracellular and intracellular regions of csGPCRs, possibly resulting in advantages during adaptation by affecting protein degradation and the sensing of environmental cues, respectively.

Refined mapping of stripe rust resistance gene YrP10090 within a desirable haplotype for wheat improvement on chromosome 6A.

A large genomic region spanning over 300 Mb on chromosome 6A under intense artificial selection harbors multiple loci associated with favorable traits including stripe rust resistance in wheat. The development of resistance cultivars can be an optimal strategy for controlling wheat stripe rust disease. Although loci for stripe rust resistance have been identified on chromosome 6A in previous studies, it is unclear whether these loci span a common genetic interval, and few studies have attempted to analyze the haplotype changes that have accompanied wheat improvement over the period of modern breeding. In this study, we used F2:3 families and F6:7 recombinant inbred lines (RILs) derived from a cross between a resistant CIMMYT wheat accession P10090 and the susceptible landrace Mingxian 169 to improve the resolution of the QTL on chromosome 6A. The co-located QTL, designated as YrP10090, was flanked by SNP markers AX-94460938 and AX-110585473 with a genetic interval of 3.5cM, however, corresponding to a large physical distance of over 300Mb in RefSeq v.1.0 (positions 107.1-446.5Mb). More than 1,300 SNP markers in this genetic region were extracted for haplotype analysis in a panel of 1,461 worldwide common wheat accessions, and three major haplotypes (Hap1, Hap2, and Hap3) were identified. The favorable haplotype Hap1 associated with stripe rust resistance exhibited a large degree of linkage disequilibrium. Selective sweep analyses were performed between different haplotype groups, revealing specific genomic regions with strong artificial selection signals. These regions harbored multiple desirable traits associated with resilience to environmental stress, different yield components, and quality characteristics. P10090 and its derivatives that carry the desirable haplotype can provide a concrete foundation for bread wheat improvement including the genomic selection.

Coconut genome assembly enables evolutionary analysis of palms and highlights signaling pathways involved in salt tolerance

Coconut (Cocos nucifera) is the emblematic palm of tropical coastal areas all around the globe. It provides vital resources to millions of farmers. In an effort to better understand its evolutionary history and to develop genomic tools for its improvement, a sequence draft was recently released. Here, we present a dense linkage map (8402 SNPs) aiming to assemble the large genome of coconut (2.42 Gbp, 2n = 32) into 16 pseudomolecules. As a result, 47% of the sequences (representing 77% of the genes) were assigned to 16 linkage groups and ordered. We observed segregation distortion in chromosome Cn15, which is a signature of strong selection among pollen grains, favouring the maternal allele. Comparing our results with the genome of the oil palm Elaeis guineensis allowed us to identify major events in the evolutionary history of palms. We find that coconut underwent a massive transposable element invasion in the last million years, which could be related to the fluctuations of sea level during the glaciations at Pleistocene that would have triggered a population bottleneck. Finally, to better understand the facultative halophyte trait of coconut, we conducted an RNA-seq experiment on leaves to identify key players of signaling pathways involved in salt stress response. Altogether, our findings represent a valuable resource for the coconut breeding community.

Fine scale human genetic structure in three regions of Cameroon reveals episodic diversifying selection

Inferences from genetic association studies rely largely on the definition and description of the underlying populations that highlight their genetic similarities and differences. The clustering of human populations into subgroups (population structure) can significantly confound disease associations. This study investigated the fine-scale genetic structure within Cameroon that may underlie disparities observed with Cameroonian ethnicities in malaria genome-wide association studies in sub-Saharan Africa. Genotype data of 1073 individuals from three regions and three ethnic groups in Cameroon were analyzed using measures of genetic proximity to ascertain fine-scale genetic structure. Model-based clustering revealed distinct ancestral proportions among the Bantu, Semi-Bantu and Foulbe ethnic groups, while haplotype-based coancestry estimation revealed possible longstanding and ongoing sympatric differentiation among individuals of the Foulbe ethnic group, and their Bantu and Semi-Bantu counterparts. A genome scan found strong selection signatures in the HLA gene region, confirming longstanding knowledge of natural selection on this genomic region in African populations following immense disease pressure. Signatures of selection were also observed in the HBB gene cluster, a genomic region known to be under strong balancing selection in sub-Saharan Africa due to its co-evolution with malaria. This study further supports the role of evolution in shaping genomes of Cameroonian populations and reveals fine-scale hierarchical structure among and within Cameroonian ethnicities that may impact genetic association studies in the country.

Rapid and Parallel Adaptive Mutations in Spike S1 Drive Clade Success in SARS-CoV-2

Despite the appearance of variant SARS-CoV-2 viruses with altered receptorbinding or antigenic phenotypes, traditional methods for detecting adaptive evolution from sequence data do not pick up strong signals of positive selection. Here, we present a new method for identifying adaptive evolution on short evolutionary time scales with densely-sampled populations. We apply this method to SARS-CoV-2 to perform a comprehensive analysis of adaptively-evolving regions of the genome. We find that spike S1 is a focal point of adaptive evolution, but also identify positivelyselected mutations in other genes that are sculpting the evolutionary trajectory of SARS-CoV-2. Protein-coding mutations in S1 are temporally-clustered and, in 2021, the ratio of nonsynonymous to synonymous divergence in S1 is more than 4 times greater than in the equivalent influenza HA1 subunit. Funding: This work was supported by NIH R35 GM119774. KEK was supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1762114. Declaration of Interests: None to declare.