The Population Diversity of Candidate Genes for Resistance/Susceptibility to Coronavirus Infection in Domestic Cats: An Inter-Breed Comparison

Vychodilova

et al. 2022

HLA

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Natural killer cells and cytotoxic T lymphocytes are the main cell populations of the immune system able to directly kill target cells via cytotoxic granules. Different mammalian species may differ in specific features of their pore‐forming protein (perforin) and granule‐bound serine proteases (granzymes). One perforin gene (PRF1) and four genes encoding granzymes A, B, H, and K (GZMA, GZMB, GZMH, GZMK) were identified in the reference genomes of felids. The objective of this work was to characterize the genes PRF1, GZMA and GZMB in a panel of 17 felid species by next‐generation re‐sequencing. A search of available felid genomes (17 species) retrieved the coding sequences of these genes for comparison to our data. Both sets of sequences or their combinations (23 species) were used for phylogenetic and selection analyses. Nucleotide PRF1, GZMA and GZMB sequences showed high similarities between felid species (over 95% identity). All trees derived from coding sequences expressed phylogenetic relationships corresponding to the zoological taxonomy of the Felidae, except GZMA. No effects of positive selection were detected in the genes studied, however, effects of purifying selection were observed for PRF1 and GZMA. The conservation of PRF1 is in agreement with its critical biological function. The differentiation observed between granzyme sub‐families may reflect an adaptation to pathogen variation. The need to maintain important gene functions and at the same time cope with various pathogens may lead to an equilibrium between positive and negative selective pressures acting on GZMB. The within‐species variability in wild felid populations merits further investigation.

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 61%

The deadly face of felid killer cells: The cytotoxic proteins and their genes

Futas

Vychodilova

et al. 2022

HLA

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“…The observed variation of NCR1 raises questions about its functional importance. In our previous studies, an NCR1 SNP was associated with a greater risk of persistent fecal shedding and with a higher load of Feline Enteric Coronavirus (FECV) particles in domestic cats 16,36 . Persistent shedders represent an important epidemiological risk not only for FECV infection, but also for Feline Infectious Peritonitis caused by a mutant FECV biotype 37 .…”

Section: Discussionmentioning

confidence: 98%

“…In our previous studies, an NCR1 SNP was associated with a greater risk of persistent fecal shedding and with a higher load of Feline Enteric Coronavirus (FECV) particles in domestic cats. 16,36 Persistent shedders represent an important epidemiological risk not only for FECV infection, but also for Feline Infectious Peritonitis caused by a mutant FECV biotype. 37 Interestingly, the susceptibility-associated allele was detected in all felid species examined here.…”

Section: The Diversity Of Ncr Genes In Domestic Catsmentioning

confidence: 99%

The natural cytotoxicity receptor genes in the family Felidae

Bubeníkova

Futas

et al. 2022

HLA

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Natural killer (NK) cells belong to the innate immune system. The germline‐encoded natural killer cell receptors represent activating and inhibitory receptors regulating multiple NK cell activities. The natural cytotoxicity receptors (NCRs) are activating natural cytotoxicity triggering receptors 1, 2, and 3 (NKp46, NKp44, and NKp30), encoded by the genes NCR1, NCR2, and NCR3, respectively. NCRs may be expressed in different cell types engaged in mechanisms of innate and adaptive immunity. The family Felidae, comprising the domestic cat and a wide variety of free‐ranging species represents a well‐suited model for biomedical and evolutionary studies. We characterized the NCR1, NCR2, and NCR3 genes in a panel of felid species. We confirmed the presence of potentially functional genes NCR1, NCR2, and NCR3 in all species. All three genes are conserved within the family and are similar to other phylogenetically related mammalian families. The NCR1 and NCR2 phylogenetic trees based on both nucleotide and protein sequences corresponded to the current zoological taxonomy, with some exceptions suggesting effects of different selection pressures in some species. Highly conserved NCR3 sequences did not allow a robust phylogenetic analysis. Most interspecific differences both at the nucleotide and protein level were found in NCR2. Within species, the most polymorphic CDS was detected in NCR1. Selection analyses indicated the effects of purifying selection on individual amino acid sites in all three genes. In stray cats, a rather high intraspecific diversity was observed.

“…36 Consensus sequences were determined by bcftools (v1.11). 37 The bioinformatic analysis of Illumina data was performed as described in our previous paper, for details see Bubenikova et al 2021. 38 Briefly, preprocessing included use of FastQC (v. 0.11.5) and Trimmomatic (v. 0.36).…”

Section: Bioinformatic Analysismentioning

confidence: 99%

Newly identified variability of the antigen binding site coding sequences of the equine major histocompatibility complex class I and class II genes

Plášil

Klumplerová

et al. 2023

HLA

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The major histocompatibility complex (MHC) with its class I and II genes plays a crucial role in the immune response to pathogens by presenting oligopeptide antigens to various immune response effector cells. In order to counteract the vast variability of infectious agents, MHC class I and II genes usually retain high levels of SNPs mainly concentrated in the exons encoding the antigen binding sites. The aim of the study was to reveal new variability of selected MHC genes with a special focus on MHC class I physical haplotypes. Long‐range NGS to was used to identify exon 2–exon 3 alleles in three genetically distinct horse breeds. A total of 116 allelic variants were found in the MHC class I genes Eqca‐1, Eqca‐2, Eqca‐7 and Eqca‐Ψ, 112 of which were novel. The MHC class II DRA locus was confirmed to comprise five exon 2 alleles, and no new sequences were observed. Additional variability in terms of 15 novel exon 2 alleles was identified in the DQA1 locus. Extensive overall variability across the entire MHC region was confirmed by an analysis of MHC‐linked microsatellite loci. Both diversifying and purifying selection were detected within the MHC class I and II loci analyzed.