balancing selection
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2023 ◽  
Vol 83 ◽  
M. Ahsan ◽  
M. Ashfaq ◽  
H. Riaz ◽  
Z. Khan ◽  
M. Z. Hamza ◽  

Abstract Cucumber mosaic virus (CMV) is a tremendous threat to vegetables across the globe, including in Pakistan. The present work was conducted to investigate the genetic variability of CMV isolates infecting pea and spinach vegetables in the Pothwar region of Pakistan. Serological-based surveys during 2016-2017 revealed 31.70% overall CMV disease incidence from pea and spinach crops. Triple-antibody sandwich enzyme-linked immunosorbent assay (TAS-ELISA) revealed that all the positive isolates belong to CMV subgroup II. Two selected cDNA from ELISA-positive samples representing each pea and spinach crops were PCR-amplified (ca.1100 bp) and sequenced corresponding to the CMV CP gene which shared 93.7% nucleotide identity with each other. Both the sequences of CMV pea (AAHAP) and spinach (AARS) isolates from Pakistan were submitted to GenBank as accession nos. MH119071 and MH119073, respectively. BLAST analysis revealed 93.4% sequence identity of AAHAP isolate with SpK (KC763473) from Iran while AARS isolate shared maximum identity (94.5%) with the strain 241 (AJ585519) from Australia and clustered with some reference isolates of CMV subgroup II from UK (Z12818) and USA (AF127976) in a Neighbour-joining phylogenetic reconstruction. A total of 59 polymorphic (segregating) sites (S) with nucleotide diversity (π) of 0.06218 was evident while no INDEL event was observed in Pakistani isolates. The evolutionary distance of Pakistani CMV isolates was recorded as 0.0657 with each other and 0.0574-0.2964 with other CMV isolates reported elsewhere in the world. A frequent gene flow (Fst = 0.30478 <0.33) was observed between Pakistani and earlier reported CMV isolates. In genetic differentiation analysis, the value of three permutation-based statistical tests viz; Z (84.3011), Snn (0.82456), and Ks* (4.04042) were non-significant. The statistical analysis revealed the values 2.02535, 0.01468, and 0.71862 of Tajima's D, Fu, & Li’s F* and D* respectively, demonstrating that the CMV population is under balancing selection.

2022 ◽  
Suo Qiu ◽  
James M. Bradley ◽  
Peijun Zhang ◽  
Roy Chaudhuri ◽  
Mark Blaxter ◽  

Parasites have evolved suites of proteins, Virulence Factors (VFs), that are delivered into host plants to facilitate colonization. Whilst VFs mediating plant-microbe and plant-nematode interactions have been characterised extensively, less is known about VFs mediating parasitic plant interactions with their hosts. Striga hermonthica is an obligate, root-parasitic plant capable of parasitizing multiple cereal hosts in sub-Saharan Africa, causing devastating losses in yields. An understanding of the molecular nature and allelic variation of VFs in S. hermonthica is essential for breeding durable resistance and delaying the evolution of parasite virulence. To address this issue, we assembled a genome for Striga hermonthica and identified candidate VFs by combining in silico prediction of secreted proteins with pooled sequencing of parasites growing on a susceptible and a strongly resistant rice host. Consistent with predictions for parasites, like S. hermonthica, that can interact with multiple hosts, we identified multiple loci, potentially with a wide range of functions, implicated in overcoming host resistance. Extremely different allele frequencies were observed at 152 non-secreted and 38 putatively secreted VFs between S. hermonthica parasitising the resistant and susceptible rice varieties. Our candidate, secreted VFs encompassed functions such as host cell wall modification, protease inhibitors, oxidoreductase and kinase activities, as well as several with unknown functions. Consistent with maintenance of variation at virulence loci by balancing selection the candidate loci had significantly higher Tajima’s D on average than the genomic background. Our results show that diverse strategies are used by  S. hermonthica  to overcome different layers of host resistance. Understanding the maintenance of variation at virulence loci by balancing selection will be critical to managing the evolution of virulence as a part of a sustainable control strategy.

2022 ◽  
Lorenzo Talarico ◽  
Anna Bryjová ◽  
Dagmar Čížková ◽  
Karel Douda ◽  
Martin Reichard

AbstractPolymorphism of the major histocompatibility complex (MHC), DAB1 gene was characterized for the first time in the European bitterling (Rhodeus amarus), a freshwater fish employed in studies of host-parasite coevolution and mate choice, taking advantage of newly designed primers coupled with high-throughput amplicon sequencing. Across 221 genotyped individuals, we detected 1–4 variants per fish, with 28% individuals possessing 3–4 variants. We identified 36 DAB1 variants, and they showed high sequence diversity mostly located within predicted antigen-binding sites, and both global and codon-specific excess of non-synonymous mutations. Despite deep divergence between two major allelic lineages, functional diversity was surprisingly low (3 supertypes). Overall, these findings suggest the role of positive and balancing selection in promotion and long-time maintenance of DAB1 polymorphism. Further investigations will clarify the role of pathogen-mediated selection to drive the evolution of DAB1 variation.

2021 ◽  
Jun Ishigohoka ◽  
Karen Bascón-Cardozo ◽  
Andrea Bours ◽  
Janina Fuß ◽  
Arang Rhie ◽  

The patterns of genetic relatedness among individuals vary along the genome, representing fluctuation of local ancestry. The factors responsible for this variation have not been well studied in wild animals with ecological and behavioural relevance. Here, we characterise the genomic architecture of genetic relatedness in the Eurasian blackcap, an iconic songbird species in ecology and quantitative genetics of migratory behaviour. We identify 23 genomic regions with deviated local relatedness patterns, using a chromosome-level de novo assembly of the blackcap genome and whole-genome resequencing data of 179 individuals from nine populations with diverse migratory phenotypes. Five genomic regions show local relatedness patterns of polymorphic inversions, three of which are syntenic to polymorphic inversions known in the zebra finch. Phylogenetic analysis reveals these three polymorphic inversions evolved independently in the blackcap and zebra finch indicating convergence of polymorphic inversions. Population genetic analyses in these three inversions in the blackcap suggest balancing selection between two haplotypes in one locus and background selection in the other two loci. One genomic region with deviated local relatedness is under selection against gene flow by population-specific reduction in recombination rate. Other genomic islands including 11 pericentromeric regions consist of evolutionarily conserved and non-conserved recombination cold-spots under background selection. Two of these regions with non-conserved recombination suppression are known to be associated with population-specific migratory phenotypes, where local relatedness patterns support additional effects of population-specific selection. These results highlight how different forms of recombination suppression and selection jointly affect heterogeneous genomic landscape of local ancestries.

2021 ◽  
Diala Abu Awad ◽  
Donald M Waller

Classical models ignoring linkage predict that deleterious recessive mutations purge or fix within inbred populations, yet these often retain moderate to high segregating load. True overdominance generates balancing selection that sustains inbreeding depression even in inbred populations but is rare. In contrast, arrays of mildly deleterious recessives linked in repulsion may occur commonly enough to generate pseudo-overdominance and sustain segregating load. We used simulations to explore how long pseudo-overdominant regions (POD's) persist following their creation via hybridization between populations fixed for alternative mutations at linked loci. Balancing haplotype loads, tight linkage, and moderate to strong cumulative selective effects serve to maintain POD's, suggesting that POD's may most often arise and persist in low recombination regions (e.g., inversions). Selection and drift unbalance the load, eventually eliminating POD's, but this process is very slow when pseudo-overdominance is strong. Background selection across the genome accelerates the loss of weak POD's but reinforces strong POD's in inbred populations by disfavoring homozygotes. Further modeling and studies of POD dynamics within populations could help us understand how POD's affect persistence of the load and how inbred mating systems evolve.

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260692
Jessica Allingham ◽  
Wely B. Floriano

Fertilization in mammals begins with the union of egg and sperm, an event that starts a cascade of cellular processes. The molecular-level understanding of these processes can guide the development of new strategies for controlling and/or promoting fertilization, and inform researchers and medical professional on the best choice of interventions. The proteins encoded by the IZUMO1 and JUNO genes form a ligand-receptor protein pair involved in the recognition of sperm and egg. Due to their role in the fertilization process, these proteins are potential targets for the development of novel anti-contraceptive, as well as infertility treatments. Here we present a comprehensive analysis of these gene sequences, with the objective of identifying evolutionary patterns that may support their relevance as targets for preventing or improving fertility among humans. JUNO and IZUMO1 gene sequences were identified within the genomes of over 2,000 humans sequenced in the 1000 Genomes Project. The human sequences were subjected to analyses of nucleotide diversity, deviation from neutrality of genetic variation, population-based differentiation (FST), haplotype inference, and whole chromosome scanning for signals of positive or of balancing selection. Derived alleles were determined by comparison to archaic hominin and other primate genomes. The potential effect of common non-synonymous variants on protein-protein interaction was also assessed. IZUMO1 displays higher variability among human individuals than JUNO. Genetic differentiation between continental population pairs was within whole-genome estimates for all but the JUNO gene in the African population group with respect to the other 4 population groups (American, East Asian, South Asian, and European). Tajima’s D values demonstrated deviation from neutrality for both genes in comparison to a group of genes identified in the literature as under balancing or positive selection. Tajima’s D for IZUMO1 aligns with values calculated for genes presumed to be under balancing selection, whereas JUNO’s value aligned with genes presumed to be under positive selection. These inferences on selection are both supported by SNP density, nucleotide diversity and haplotype analysis. A JUNO haplotype carrying 3 derived alleles out of 5, one of which is a missense mutation implicated in polyspermy, was found to be significant in a population of African ancestry. Polyspermy has a disadvantageous impact on fertility and its presence in approximately 30% of the population of African ancestry may be associated to a potentially beneficial role of this haplotype. This role has not been established and may be related to a non-reproductive role of JUNO. The high degree of conservation of the JUNO sequence combined with a dominant haplotype across multiple population groups supports JUNO as a potential target for the development of contraceptive treatments. In addition to providing a detailed account of human genetic diversity across these 2 important and related genes, this study also provides a framework for large population-based studies investigating protein-protein interactions at the genome level.

2021 ◽  
Vol 12 ◽  
Martijn F. L. Derks ◽  
Marije Steensma

Harmful alleles can be under balancing selection due to an interplay of artificial selection for the variant in heterozygotes and purifying selection against the variant in homozygotes. These pleiotropic variants can remain at moderate to high frequency expressing an advantage for favorable traits in heterozygotes, while harmful in homozygotes. The impact on the population and selection strength depends on the consequence of the variant both in heterozygotes and homozygotes. The deleterious phenotype expressed in homozygotes can range from early lethality to a slightly lower fitness in the population. In this review, we explore a range of causative variants under balancing selection including loss-of-function variation (i.e., frameshift, stop-gained variants) and regulatory variation (affecting gene expression). We report that harmful alleles often affect orthologous genes in different species, often influencing analogous traits. The recent discoveries are mainly driven by the increasing genomic and phenotypic resources in livestock populations. However, the low frequency and sometimes subtle effects in homozygotes prevent accurate mapping of such pleiotropic variants, which requires novel strategies to discover. After discovery, the selection strategy for deleterious variants under balancing selection is under debate, as variants can contribute to the heterosis effect in crossbred animals in various livestock species, compensating for the loss in purebred animals. Nevertheless, gene-assisted selection is a useful tool to decrease the frequency of the harmful allele in the population, if desired. Together, this review marks various deleterious variants under balancing selection and describing the functional consequences at the molecular, phenotypic, and population level, providing a resource for further study.

2021 ◽  
Sayran Saber ◽  
Michael Snyder ◽  
Moein Rajaei ◽  
Charles F. Baer

C. elegans strains with the mortal germline (Mrt) phenotype become progressively sterile over the course of a few tens of generations. Mrt is proximately controlled epigenetically, and is typically temperature-dependent, being penetrant at temperatures near the upper range of C. elegans' tolerance. Previous studies have suggested that Mrt presents a relatively large mutational target, and that Mrt is not uncommon in natural populations of C. elegans. The Mrt phenotype is not monolithic. Some strains exhibit a strong Mrt phenotype, in which individuals invariably become sterile over a few generations, whereas other strains show a weaker (less penetrant) phenotype in which the onset of sterility is slower and more stochastic. We present results in which we (1) quantify the rate of mutation to the Mrt phenotype, and (2) quantify the frequency of Mrt in a collection of 95 wild isolates. Over the course of ~16,000 meioses, we detected one mutation to a strong Mrt phenotype, resulting in a point estimate of the mutation rate UMrt 6 10-5/genome/generation. We detected no mutations to a weak Mrt phenotype. 5/95 wild isolates had a strong Mrt phenotype, and although quantification of the weak Mrt phenotype is inexact, the weak Mrt phenotype is not rare in nature. We estimate a strength of selection against mutations conferring the strong Mrt phenotype 0.1%, similar to selection against mutations affecting competitive fitness. The appreciable frequency of weak Mrt variants in nature combined with the low mutation rate suggests that Mrt may be maintained by balancing selection.

2021 ◽  
Doko-Miles Thorburn ◽  
Kostas Sagonas ◽  
Tobias Lenz ◽  
Frederic Chain ◽  
Philine Feulner ◽  

Abstract Balancing selection describes evolutionary processes that maintain genetic diversity. To date, the number of impacted genes and underlying biological functions remain elusive. Using 60 three-spined stickleback genomes (Gasterosteus aculeatus) from five recently diverged lake-river population-pairs, we performed genome-wide scans across two levels of organization: population-pairs and populations. We overlapped Tajima’s D and Watterson’s estimator metrics and verified signals with additional summary statistics, and evaluated alternative explanations: neutral evolution, population structure, associated overdominance, or demographic change. Candidate windows exhibiting signals of balancing selection spanned 2.31% (population-pair) and 3.10% (population) of the autosomes. These candidate windows had extended linkage disequilibrium and were enriched in intergenic and non-synonymous SNPs. We identified 715 (population-pair) and 1,010 (population) candidate genes under balancing selection. Importantly, using conservative thresholds, we found a small proportion of candidate genes overlapped with highly differentiated loci or regions of potential associated overdominance. There was little evidence of confounding effects originating from demographic change. Overall, candidate genes under balancing selection were associated with functions related to interactions with the environment (olfaction and receptor signalling pathways). Our results demonstrate selection that maintains standing genetic variation is common and evolves in response to local environmental pressures, playing an important role in adaptation.

2021 ◽  
Vol 11 (1) ◽  
Erick C. Castelli ◽  
Bibiana S. de Almeida ◽  
Yara C. N. Muniz ◽  
Nayane S. B. Silva ◽  
Marília R. S. Passos ◽  

AbstractHLA-G is a promiscuous immune checkpoint molecule. The HLA-G gene presents substantial nucleotide variability in its regulatory regions. However, it encodes a limited number of proteins compared to classical HLA class I genes. We characterized the HLA-G genetic variability in 4640 individuals from 88 different population samples across the globe by using a state-of-the-art method to characterize polymorphisms and haplotypes from high-coverage next-generation sequencing data. We also provide insights regarding the HLA-G genetic diversity and a resource for future studies evaluating HLA-G polymorphisms in different populations and association studies. Despite the great haplotype variability, we demonstrated that: (1) most of the HLA-G polymorphisms are in introns and regulatory sequences, and these are the sites with evidence of balancing selection, (2) linkage disequilibrium is high throughout the gene, extending up to HLA-A, (3) there are few proteins frequently observed in worldwide populations, with lack of variation in residues associated with major HLA-G biological properties (dimer formation, interaction with leukocyte receptors). These observations corroborate the role of HLA-G as an immune checkpoint molecule rather than as an antigen-presenting molecule. Understanding HLA-G variability across populations is relevant for disease association and functional studies.

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