Understanding the evolution of immune genes in jawed vertebrates.

Driven by co-evolution with pathogens, host immunity continuously adapts to optimize defence against pathogens within a given environment. Recent advances in genetics, genomics and transcriptomics have enabled a more detailed investigation into how immunogenetic variation shapes the diversity of immune responses seen across domestic and wild animal species. However, a deeper understanding of the diverse molecular mechanisms that shape immunity within and among species is still needed to gain insight into-and generate evolutionary hypotheses on-the ultimate drivers of immunological differences. Here, we discuss current advances in our understanding of molecular evolution underpinning jawed vertebrate immunity. First, we introduce the immunome concept, a framework for characterizing genes involved in immune defence from a comparative perspective, then we outline how immune genes of interest can be identified. Second, we focus on how different selection modes are observed acting across groups of immune genes and propose hypotheses to explain these differences. We then provide an overview of the approaches used so far to study the evolutionary heterogeneity of immune genes on macro and microevolutionary scales. Finally, we discuss some of the current evidence as to how specific pathogens affect the evolution of different groups of immune genes. This review results from the collective discussion on the current key challenges in evolutionary immunology conducted at the ESEB 2021 Online Satellite Symposium: Molecular evolution of the vertebrate immune system, from the lab to natural populations.

Association of Variants in Innate Immune Genes TLR4 and TLR5 with Reproductive and Milk Production Traits in Czech Simmental Cattle.

Bovine genes TLR4 and TLR5, which encode antibacterial toll-like receptors, were screened for polymorphisms in Czech Red Pied (Czech Simmental) cattle to identify variants associated with reproduction, udder health, and milk production traits. Variants were discovered by hybrid resequencing of 164 bulls using HiSeq X-Ten and PacBio technologies and then individually genotyped. Nominal p-values < 0.05 for associations were detected in 18 combinations between 14 polymorphisms and 15 traits using one-way analysis of variance (ANOVA). The TLR4 variants g.610C>T (rs43578094) and g.10310T>G (rs8193072) in reference AC000135.1 were strictly associated with the index of early reproductive disorders and maternal calving ease, respectively, at false discovery rate (FDR) < 0.05. A highly permissive false discovery rate cutoff of 0.6 separated seventeen combinations in both genes comprising eight positives. In the case of the TLR4 variant g.9422T>C (rs8193060), indications were obtained for the association with as many as four reproductive traits: incidence of cystic ovaries, early reproductive disorders, calving ease, and production longevity. The permissive FDR interpretation for the TLR5 data indicated associations with cyst incidence and early reproduction disorders with maternal calving ease. Moreover, three TLR5 polymorphisms correlated with milk production traits. The discrepancy of the observed associations with the predicted impacts of the SNPs on protein function points to the role of haplotypes. Nevertheless, this question should be resolved on a larger scale. The observed associations are endorsed by independent evidence from the published functional roles in other species and by the published QTL mapping data.

Potential of TLR-gene diversity in Czech indigenous cattle for resistance breeding as revealed by hybrid sequencing.

A production herd of Czech Simmental cattle (Czech Red Pied, CRP), the conserved subpopulation of this breed, and the ancient local breed Czech Red cattle (CR) were screened for diversity in the antibacterial toll-like receptors (TLRs), which are members of the innate immune system. Polymerase chain reaction (PCR) amplicons of TLR1, TLR2, TLR4, TLR5, and TLR6 from pooled DNA samples were sequenced with PacBio technology, with 3- 5 × â€¯coverage per gene per animal. To increase the reliability of variant detection, the gDNA pools were sequenced in parallel with the Illumina X-ten platform at low coverage ( 60 × per gene). The diversity in conserved CRP and CR was similar to the diversity in conserved and modern CRP, representing 76.4 % and 70.9 % of its variants, respectively. Sixty-eight (54.4 %) polymorphisms in the five TLR genes were shared by the two breeds, whereas 38 (30.4 %) were specific to the production herd of CRP; 4 (3.2 %) were specific to the broad CRP population; 7 (5.6 %) were present in both conserved populations; 5 (4.0 %) were present solely for the conserved CRP; and 3 (2.4 %) were restricted to CR. Consequently, gene pool erosion related to intensive breeding did not occur in Czech Simmental cattle. Similarly, no considerable consequences were found from known bottlenecks in the history of Czech Red cattle. On the other hand, the distinctness of the conserved populations and their potential for resistance breeding were only moderate. This relationship might be transferable to other non-abundant historical cattle breeds that are conserved as genetic resources. The estimates of polymorphism impact using Variant Effect Predictor and SIFT software tools allowed for the identification of candidate single-nucleotide polymorphisms (SNPs) for association studies related to infection resistance and targeted breeding. Knowledge of TLR-gene diversity present in Czech Simmental populations may aid in the potential transfer of variant characteristics from other breeds.