Fiona M. McCarthy

Scavenger Receptor (SCAR) genes are a heterogeneous group involved in innate immunity and immunomodulation. While standardized gene nomenclature is provided for model organism SCAR genes, ungulates have novel SCAR genes which have not been systematically classified. This study compares SCAR genes for five representative ungulate species which are selected based on their agricultural importance and representation. We identify and classify twenty-seven SCAR genes common to all species and provide standardized gene nomenclature for genes novel to these ungulate species. Notably, we provide standardized gene nomenclature for the previously studied Workshop Cluster 1 (WC1) genes which are absent in model organisms.

Scavenger Receptors (SCARs) are a heterogeneous group involved in innate immunity and immunomodulation. We provided standardized nomenclature for chicken SCAR genes in line with other vertebrate nomenclatures. Chicken SCAR genes orthologous to human genes are assigned the same gene names and symbols. Novel SCAR genes were assessed to determine their appropriate class and assigned nomenclature in line with this classification. Notably, chicken has expansions of the MRC and DMBT genes, and the number of these paralogs varies across Sauropsida species. In addition, we identified and classified a further 15 novel SCAR genes, predominantly SCAR class I genes.

As amniote vertebrates, lizards are the most closely related organisms to humans capable of appendage regeneration. Lizards can autotomize, or release their tails as a means of predator evasion, and subsequently regenerate a functional replacement. Green anoles (Anolis carolinensis) can regenerate their tails through a process that involves differential expression of hundreds of genes, which has previously been analyzed by transcriptomic and microRNA analysis. To investigate protein expression in regenerating tissue, we performed a whole proteomic analysis of regenerating tail tip and base. This is the first proteomic data set available for any anole lizard. We identified a total of 2646 proteins—976 proteins only in the regenerating tail base, 796 only in the tail tip, and 874 in both tip and base. For over 90% of these proteins in these tissues, we were able to assign a clear orthology to gene models in either the Ensembl or NCBI databases. For 13 proteins in the tail base, 9 proteins in the tail tip, and 10 proteins in both regions, the gene model in Ensembl and NCBI matched an uncharacterized protein, confirming that these predictions are present in the proteome. Ontology and pathways analysis of proteins expressed in the regenerating tail base identified categories, including actin filament‐based process, ncRNA metabolism, regulation of phosphatase activity, small GTPase‐mediated signal transduction, and cellular component organization or biogenesis. Analysis of proteins expressed in the tail tip identified categories, including regulation of organelle organization, regulation of protein localization, ubiquitin‐dependent protein catabolism, small GTPase‐mediated signal transduction, morphogenesis of epithelium, and regulation of biological quality. These proteomic findings confirm pathways and gene families activated in tail regeneration in the green anole as well as identify uncharacterized proteins whose role in regrowth remains to be revealed. This study demonstrates the insights that are possible from the integration of proteomic and transcriptomic data in tail regrowth in the green anole, with potentially broader application to studies in other regenerative models.KEY POINTS: This research is highly interdisciplinary, combining our previous analyses with these most recent findings: Appendage regeneration is a conserved trait among vertebrates and has been characterized in animals ranging from teleost fish (zebrafish), urodele amphibians (axolotl), anuran amphibians (Xenopus frog), squamate reptiles (various species of lizards), and even crocodilians (American alligator). Comparative genomic and proteomic analysis of this process allows us to identify the genetic pathways and cellular processes under evolutionary selection for this regrowth capacity. Activating these conserved genetic pathways and cellular processes will be critical to developing regenerative medical therapies in humans. The identification of proteins expressed in regeneration extends analyses based only on predicted proteins from transcriptomic analysis, and permits integration with protein‐expression studies of regrowing nervous and musculoskeletal structures.

Chicken domestication began at least 3,500 years ago for purposes of divination, cockfighting, and food. Prior to industrial scale chicken production, domestication selected larger birds with increased egg production. In the mid-20^th century companies began intensive selection with the broiler (meat) industry focusing on improved feed conversion, rapid growth, and breast muscle yield. Here we present proteomic analysis comparing the modern broiler line, Ross 708, with the UIUC legacy line which is not selected for growth traits. Breast muscle proteome analysis identifies cellular processes that have responded to human directed artificial selection. Mass spectrometry was used to identify protein level differences in the breast muscle of 6-day old chicks from Modern and Legacy lines. Our results indicate elevated levels of stress proteins, ribosomal proteins and proteins that participate in the innate immune pathway in the Modern chickens. Furthermore, the comparative analyses indicated expression differences for proteins involved in multiple biochemical pathways. In particular, the Modern line had elevated levels of proteins affecting the pentose phosphate pathway, TCA cycle and fatty acid oxidation while proteins involved in the first phase of glycolysis were reduced compared to the Legacy line. These analyses provide hypotheses linking the morphometric changes driven by human directed selection to biochemical pathways. These results also have implications for the poultry industry, specifically Wooden Breast disease which is linked to rapid breast muscle growth.

Chicken domestication began at least 3,500 years ago for purposes of divination, cockfighting, and food. Prior to industrial scale chicken production, domestication selected larger birds with increased egg production. In the mid-20 ^th century companies began intensive selection with the broiler (meat) industry focusing on improved feed conversion, rapid growth, and breast muscle yield. Here we present proteomic analysis comparing the Ross 708 modern broiler line with the UIUC legacy line. Comparing the breast muscle proteome between modern broilers and legacy lines not selected for these growth traits identifies cellular processes that have responded to human directed evolution. Mass spectrometry was used to identify differences in protein levels in the breast muscle of 6-day old chicks from Modern and Legacy lines. The results highlighted elevated levels of stress proteins, ribosomal proteins, and proteins that participate in the innate immune pathway in the Modern chickens. Furthermore, the comparative analyses indicated differences in the levels of proteins involved in multiple biochemical pathways. In particular, the Modern line had elevated levels of proteins affecting the pentose phosphate pathway, TCA cycle, and fatty acid oxidation and reduced protein levels of the first phase of glycolysis. These analyses provide hypotheses linking the morphometric changes driven by human directed selection to biochemical pathways. The results also have implications for the onset of Wooden Breast disease that arose due to selection for rapid breast muscle growth and is a major problem in the poultry industry.

Background Network studies of host-pathogen interactions (HPI) are critical in understanding the mechanisms of pathogenesis. However, accessible HPI data for agriculturally important pathogens are limited. This lack of HPI data impedes network analysis to study agricultural pathogens, for preventing and reducing the severity of diseases of relevance to agriculture. Results To rapidly provide HPIs for a broad range of pathogens, we use an interolog-based approach. This approach uses sequence similarity to transfer known HPIs from better studied host-pathogen pairs and predicts 389,878 HPIs for 23 host-pathogen systems of relevance to US agriculture. Each predicted HPI is qualitatively assessed using co-localization, infection related processes, and interacting domains and this information is provided as a confidence indicator for the prediction. Evaluation of predicted HPIs demonstrates that the host proteins predicted to be involved in pathogen interactions include hubs and bottlenecks in the network, as reported in curated host proteins. Moreover, we demonstrate that the use of the predicted HPIs adds value to network analysis and recapitulates known aspects of host-pathogen biology. Access to the predicted HPIs for these agricultural host-pathogen systems is available via the Host Pathogen Interaction Database (HPIDB, hpidb.igbb.msstate.edu), and can be downloaded in standard MITAB file format for subsequent network analysis. Conclusions This core set of interolog-based HPIs will enable animal health researchers to incorporate network analysis into their research and help identify host-pathogen interactions that may be tested and experimentally validated. Moreover, the development of a larger set of experimentally validated HPI will inform future predictions. Our approach of transferring biologically relevant HPIs based on interologs is broadly applicable to many host-microbe systems and can be extended to support network modeling of other pathogens, as well as interactions between non-pathogenic microbes.