Balancing selection is a classic mechanism for maintaining variability in immune genes involved in host-pathogen interactions. However, it remains unclear how widespread the mechanism is across immune genes other than the major histocompatibility complex (MHC). Although occasional reports suggest that balancing selection (heterozygote advantage, negative frequency-dependent selection, and fluctuating selection) may act on other immune genes, the current understanding of the phenomenon in non-MHC immune genes is far from solid. In this review, we focus on Toll-like receptors (TLRs), innate immune genes directly involved in pathogen recognition and immune response activation, as there is a growing body of research testing the assumptions of balancing selection in these genes. After reviewing infection- and fitness-based evidence, along with evidence based on population allelic frequencies and heterozygosity levels, we conclude that balancing selection maintains variation in TLRs, though it tends to occur under specific conditions in certain evolutionary lineages rather than being universal and ubiquitous. Our review also identifies key gaps in current knowledge and proposes promising areas for future research. Improving our understanding of host-pathogen interactions and balancing selection in innate immune genes are increasingly important, particularly regarding threats from emerging zoonotic diseases.

• Klíčová slova
• TLR, Toll-like receptors, balancing selection, host–pathogen interactions, innate immune genes, polymorphism,
• MeSH
• frekvence genu MeSH
• hlavní histokompatibilní komplex MeSH
• polymorfismus genetický * MeSH
• přirozená imunita genetika   MeSH
• selekce (genetika) MeSH
• toll-like receptory * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• toll-like receptory * MeSH

Balancing selection is a form of natural selection maintaining diversity at the sites it targets and at linked nucleotide sites. Due to selection favoring heterozygosity, it has the potential to facilitate the accumulation of a "sheltered" load of tightly linked recessive deleterious mutations. However, precisely evaluating the extent of these effects has remained challenging. Taking advantage of plant self-incompatibility as one of the best-understood examples of long-term balancing selection, we provide a highly resolved picture of the genomic extent of balancing selection on the sheltered genetic load. We used targeted genome resequencing to reveal polymorphism of the genomic region flanking the self-incompatibility locus in three sample sets in each of the two closely related plant species Arabidopsis halleri and Arabidopsis lyrata, and used 100 control regions from throughout the genome to factor out differences in demographic histories and/or sample structure. Nucleotide polymorphism increased strongly around the S-locus in all sample sets, but only over a limited genomic region, as it became indistinguishable from the genomic background beyond the first 25-30 kb. Genes in this chromosomal interval exhibited no excess of mutations at 0-fold degenerated sites relative to putatively neutral sites, hence revealing no detectable weakening of the efficacy of purifying selection even for these most tightly linked genes. Overall, our results are consistent with the predictions of a narrow genomic influence of linkage to the S-locus and clarify how natural selection in one genomic region affects the evolution of the adjacent genomic regions.

• Klíčová slova
• Arabidopsis, S-locus, balancing selection, deleterious mutations, linked selection, self-incompatibility, sheltered genetic load,
• MeSH
• Arabidopsis * genetika   MeSH
• genetická zátěž MeSH
• nukleotidy MeSH
• polymorfismus genetický MeSH
• selekce (genetika) MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nukleotidy MeSH

Maintenance of genetic polymorphism remains one of the big questions of evolutionary biology, which for a long time tended to be explained by balancing selection. This explanation was later criticized, but now is again accepted as an important mechanism in evolution. Human blood group systems seem affected by balancing selection especially strongly. In this preregistered study, we focused on stable coexistence of RhD-positive and RhD-negative subjects in a population. This is an evolutionary conundrum, because carriers of the less frequent negative allele suffer from lower fecundity due to haemolytic disease of the newborn affecting RhD-positive infants born to RhD-negative women. One explanation of persisting stability of RhD polymorphism points to heterozygote advantage. Over the past decade, numerous studies demonstrated that RhD-positive subjects score better than RhD-negative homozygotes in psychomotor tests and physical health-related variables. Still, evidence of better health and performance of heterozygotes is scarce and merely indirect. We compared the physical and mental health of 2,539 subjects whose RhD genotype was estimated based on their and their parents' RhD phenotype. We confirmed that RhD-negative homozygotes fare worse in terms of physical and mental health than subjects with RhD-positive phenotype and that RhD-positive heterozygotes enjoy better health than both homozygotes. For the first time, we demonstrated that RhD-positive homozygotes might suffer from worse health than RhD-negative homozygotes. Our results strongly support the hypothesis that RhD polymorphism is maintained by heterozygote advantage and that balancing selection may have played an important role in human evolution in this context and in general.

• Klíčová slova
• balancing selection, frequency-dependent selection, heterozygote advantage, human evolution, polymorphism, viability,
• MeSH
• biologická evoluce * MeSH
• dospělí MeSH
• heterozygot * MeSH
• krevní skupiny - systém Rh-Hr genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• průřezové studie MeSH
• selekce (genetika) * MeSH
• zdravotní stav * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• krevní skupiny - systém Rh-Hr MeSH

The extracellular subunit of the major histocompatibility complex MHCIIβ plays an important role in the recognition of pathogens and the initiation of the adaptive immune response of vertebrates. It is widely accepted that pathogen-mediated selection in combination with neutral micro-evolutionary forces (e.g. genetic drift) shape the diversity of MHCIIβ, but it has proved difficult to determine the relative effects of these forces. We evaluated the effect of genetic drift and balancing selection on MHCIIβ diversity in 12 small populations of Galápagos mockingbirds belonging to four different species, and one larger population of the Northern mockingbird from the continental USA. After genotyping MHCIIβ loci by high-throughput sequencing, we applied a correlational approach to explore the relationships between MHCIIβ diversity and population size by proxy of island size. As expected when drift predominates, we found a positive effect of population size on the number of MHCIIβ alleles present in a population. However, the number of MHCIIβ alleles per individual and number of supertypes were not correlated with population size. This discrepancy points to an interesting feature of MHCIIβ diversity dynamics: some levels of diversity might be shaped by genetic drift while others are independent and possibly maintained by balancing selection.

• Klíčová slova
• Mimus, genetic diversity, major histocompatibility complex, population size, trans-species polymorphism,
• MeSH
• genetická variace MeSH
• genetický drift * MeSH
• genotyp MeSH
• geny MHC třídy II * MeSH
• hustota populace MeSH
• ostrovy MeSH
• Passeriformes genetika   MeSH
• populační genetika MeSH
• selekce (genetika) * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Ekvádor MeSH
• ostrovy MeSH

Compared to the negative effect of directional selection on genetic diversity, balancing selection acts oppositely and maintains variability across the genome. This study aims to articulate whether balancing selection leads to heterozygosity-rich region islands (HRRIs) forming in the canine genome by investigating 1000 animals belonging to 50 dog breeds via 153,733 autosomal SNPs. A consecutive SNP-based approach was used to identify heterozygosity-rich regions (HRRs). Signals of balancing selection in the genome of studied breeds were then assessed with Tajima's D statistics. A total of 72,062 HRRs with an average length of 324 kb were detected to be unevenly distributed across the genome. A total of 509 and 450 genomic regions were classified as HRRIs and balancing selection signals, respectively. Although the genome-wide distributions of HRRIs varied across breeds, several HRRIs were found in the same locations across multiple breeds. A total of 109 genomic regions were classified as both HRRIs and signals of balancing selection. Even though the genomic coordinates of HRRIs and balancing selection signals did not fully overlap across all genomic regions, balancing selection may play a significant role in maintaining diversity in regions associated with various cancer diseases, immune response, and bone, skin, and cartilage tissue development.

• Klíčová slova
• dog, genetic diversity, heterozygosity, runs of homozygosity,
• Publikační typ
• časopisecké články MeSH

The genes of major histocompatibility complex (MHC) provide an excellent opportunity to study host-parasite relationships because they are expected to evolve in response to parasites and variation in parasite communities. In this study, we investigated the potential role of parasite-mediated selection acting on MHC class IIB (DAB) genes in European chub (Squalius cephalus) natural populations. We found significant differences between populations in metazoan parasites, neutral and adaptive genetic diversities. The analyses based on pairwise data revealed that populations with dissimilar MHC allelic profiles were geographically distant populations with significantly different diversity in microsatellites and a dissimilar composition of parasite communities. The results from the generalized estimating equations method (GEE) on the level of individuals revealed that metazoan parasite load in European chub was influenced by the diversity of DAB alleles as well as by the diversity of neutral genetic markers and host traits reflecting condition and immunocompetence. The multivariate co-inertia analysis showed specific associations between DAB alleles and parasite species. DAB1-like alleles were more involved in associations with ectoparasites, while DAB3-like alleles were positively associated with endoparasites which could suggest potential differences between DAB genes caused by different selection pressure. Our study revealed that parasite-mediated selection is not the only variable affecting MHC diversity in European chub; however, we strongly support the role of neutral processes as the main driver of DAB diversity across populations. In addition, our study contributes to the understanding of the evolution of MHC genes in wild living fish.

• Klíčová slova
• Genetic diversity, Major histocompatibility complex, Metazoan parasites, Microsatellites, Parasite-driven balancing selection, Phylogeography,
• MeSH
• alely MeSH
• Cyprinidae genetika   MeSH
• divoká zvířata MeSH
• genetická variace * MeSH
• hlavní histokompatibilní komplex genetika   MeSH
• interakce hostitele a parazita MeSH
• mikrosatelitní repetice genetika   MeSH
• nemoci ryb parazitologie   MeSH
• parazitární nemoci u zvířat epidemiologie   genetika   parazitologie   MeSH
• paraziti MeSH
• selekce (genetika) * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

Major histocompatibility complex (MHC) genes play important role in host-parasite interactions and parasites are crucial factors influencing the population dynamics of hosts. We described the structure and diversity of exon 2 of the MHC class II DQA gene in three species of voles (Arvicolinae) exhibiting regular multi-annual fluctuations of population density and analysed the processes leading to the observed MHC polymorphism. By using cloning-sequencing methodology and capillary electrophoresis-single strand conformation polymorphism, we described seven sequences in the water, eight in the common, and seven in the bank voles coming from an area of 70 km(2) around the Nozeroy canton in the Jura Mountains (Franche Comté, France). All exon 2 sequences translate to give unique amino acid sequences and positive selection was found to act very intensively on antigen binding sites. We documented the presence of recombination at vole DQA region but its importance in generating allelic polymorphism seems to be relatively limited. For the first time within rodents, we documented the duplication of the DQA gene in all three species with both copies being transcriptionally active. Phylogenetic analysis of allelic sequences revealed extensive trans-species polymorphism within the subfamily although no alleles were shared between species in our data set. We discuss possible role of parasites in forming the recent polymorphism pattern of the DQA locus in voles.

• MeSH
• alely MeSH
• Arvicolinae genetika   imunologie   MeSH
• duplikace genu * MeSH
• elektroforéza kapilární MeSH
• fylogeneze MeSH
• geny MHC třídy II genetika   MeSH
• HLA-DQ antigeny genetika   MeSH
• HLA-DQ beta řetězec MeSH
• klonování DNA MeSH
• molekulární evoluce MeSH
• molekulární sekvence - údaje MeSH
• polymorfismus konformace jednovláknové DNA * MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• HLA-DQ antigeny MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DQbeta antigen MeSH Prohlížeč

Host-pathogen interactions are of particular interest in studies of the interplay between population dynamics and natural selection. The major histocompatibility complex (MHC) genes of demographically fluctuating species are highly suitable markers for such studies, because they are involved in initiating the immune response against pathogens and display a high level of adaptive genetic variation. We investigated whether two MHC class II genes (DQA1, DRB) were subjected to contemporary selection during increases in the density of fossorial water vole (Arvicola terrestris) populations, by comparing the neutral genetic structure of seven populations with that estimated from MHC genes. Tests for heterozygosity excess indicated that DQA1 was subject to intense balancing selection. No such selection operated on neutral markers. This pattern of selection became more marked with increasing abundance. In the low-abundance phase, when populations were geographically isolated, both overall differentiation and isolation-by-distance were more marked for MHC genes than for neutral markers. Model-based simulations identified DQA1 as an outlier (i.e. under selection) in a single population, suggesting the action of local selection in fragmented populations. The differences between MHC and neutral markers gradually disappeared with increasing effective migration between sites. In the high-abundance year, DQA1 displayed significantly lower levels of overall differentiation than the neutral markers. This gene therefore displayed stronger homogenization than observed under drift and migration alone. The observed signs of selection were much weaker for DRB. Spatial and temporal fluctuations in parasite pressure and locus-specific selection are probably the most plausible mechanisms underlying the observed changes in selection pattern during the demographic cycle.

• MeSH
• Arvicolinae genetika   MeSH
• frekvence genu MeSH
• genetická variace MeSH
• genotyp MeSH
• geny MHC třídy II genetika   MeSH
• HLA-DQ alfa řetězec MeSH
• HLA-DQ antigeny genetika   MeSH
• HLA-DR antigeny genetika   MeSH
• hustota populace MeSH
• mikrosatelitní repetice genetika   MeSH
• molekulární sekvence - údaje MeSH
• populační genetika MeSH
• sekvenční analýza DNA MeSH
• selekce (genetika) * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• HLA-DQ alfa řetězec MeSH
• HLA-DQ antigeny MeSH
• HLA-DQA1 antigen MeSH Prohlížeč
• HLA-DR antigeny MeSH

We propose a general framework for the specification of a sparse representation of millimeter wave vehicular propagation channels and apply this to both synthetic data and real-world observations from channel sounding experiments. The proposed framework is based on the c-LASSO (complex Least Absolute Shrinkage and Selection Operator) which minimizes the mean squared error of the sparse representation for a given number of degrees of freedom. By choosing the number of degrees of freedom, we balance the numerical complexity of the representation in the channel emulation against its accuracy in terms of the mean squared error. A key ingredient is the choice of basis of the representation and we discuss two options: the Fourier basis and its projection onto a given subband. The results indicate that the subband-projected Fourier basis is a low-complexity choice with high fidelity for representing clustered channel impulse responses. Finally, a sequential estimator is formulated which enforces a consistent temporal evolution of the geometry of the interacting objects in the propagation environment. We demonstrate the performance of our approach using both synthetic data and measured 60 GHz vehicular channel traces.

• Klíčová slova
• Akaike information criterion, V2X communications, channel emulation, cluster channels, mmwave, model order estimation,
• Publikační typ
• časopisecké články MeSH

African populations remain underrepresented in studies of human genetic diversity, despite a growing interest in understanding how they have adapted to the diverse environments they live in. In particular, understanding the genetic basis of immune adaptation to pathogens is of paramount importance in a continent such as Africa, where the burden of infectious diseases is a major public health challenge. In this study, we investigated the molecular variation of four Human Leukocyte Antigens (HLA) class II genes (DRB1, DQA1, DQB1 and DPB1), directly involved in the immune response to parasitic infections, in more than 1000 individuals from 23 populations across North, East, Central and West Africa. By analyzing the HLA molecular diversity of these populations in relation to various geographical, cultural and environmental factors, we identified divergent genetic profiles for several (semi-)nomadic populations of the Sahel belt as a signature of their unique demography. In addition, we observed significant genetic structuring supporting both substantial geographic and linguistic differentiations within West Africa. Furthermore, neutrality tests suggest balancing selection has been shaping the diversity of these four HLA class II genes, which is consistent with molecular comparisons between HLA genes and their orthologs in chimpanzees (Patr). However, the most striking observation comes from linear modeling, demonstrating that the prevalence of Plasmodium falciparum, the primary pathogen of malaria in Africa, significantly explains a large proportion of the nucleotide diversity observed at the DPB1 gene. DPB1*01:01, a highly frequent allele in Burkinabé populations, is identified as a potential protective allele against malaria, suggesting that strong pathogen-driven positive selection at this gene has shaped HLA variation in Africa. Additionally, two low-frequency DRB1 alleles, DRB1*08:06 and DRB1*11:02, also show significant associations with P. falciparum prevalence, supporting resistance to malaria is determined by multigenic and/or multiallelic combinations rather than single allele effects.

• Klíčová slova
• Africa, HLA, human molecular diversity, malaria, pathogen‐driven selection, plasmodium falciparum,
• Publikační typ
• časopisecké články MeSH