Host transcriptome and microbiome interactions in Holstein cattle under heat stress condition

Abstract

Climate change affects animal physiology. In particular, rising ambient temperatures reduce animal vitality due to heat stress and this can be observed at various levels which included genome, transcriptome, and microbiome. In a previous study, microbiota highly associated with changes in cattle physiology, which included rectal temperature, drooling score and respiratory score, were identified under heat stress conditions. In the present study, genes differentially expressed between individuals were selected representing different additive genetic effects toward the heat stress response in cattle in their production condition. Moreover, a correlation network analysis was performed to identify interactions between the transcriptome and microbiome for 71 Chinese Holstein cows sequenced for mRNA from blood samples and for 16S rRNA genes from fecal samples. Bioinformatics analysis was performed comprising: i) clustering and classification of 16S rRNA sequence reads, ii) mapping cows' transcripts to the reference genome and their expression quantification, and iii) statistical analysis of both data types—including differential gene expression analysis and gene set enrichment analysis. A weighted co-expression network analysis was carried out to assess changes in the association between gene expression and microbiota abundance as well as to find hub genes/microbiota responsible for the regulation of gene expression under heat stress. Results showed 1,851 differentially expressed genes were found that were shared by three heat stress phenotypes. These genes were predominantly associated with the cytokine-cytokine receptor interaction pathway. The interaction analysis revealed three modules of genes and microbiota associated with rectal temperature with which two hubs of those modules were bacterial species, demonstrating the importance of the microbiome in the regulation of gene expression during heat stress. Genes and microbiota from the significant modules can be used as biomarkers of heat stress in cattle.

Candidate genes associated with heat stress and breeding strategies to relieve its effects in dairy cattle: a deeper insight into the genetic architecture and immune response to heat stress

“…Luo et al ( 14 ) also discovered seven major candidate genes ( PMAIP1 , SBK1 , TMEM33 , GATB , CHORDC1 , RTN4IP1 and BTBD7 ) associated with physiological indicators of HS (RT, RS and DS) in Holstein cattle by weighted single-step genome-wide analysis studies (WssGWAS). In the transcriptome study by Czech et al ( 106 ), the RAB39B gene was found to be significantly associated with RT, DS and RS under HS conditions in dairy cattle. In addition, Diaz et al ( 107 ) reported five genes: E2F8 , GATAD2B , BHLHE41 , FBXO44 , and RAB39B which were significantly associated with HS in cattle.…”

“…The identification of key candidate genes responsible for variation in thermoregulation could inevitably help to improve the efficiency of selective breeding, especially for traits with low heritability in dairy cattle breeding programs. In addition, investigation of the physiological systems regulated by genes involved in thermoregulation is an area that requires further study, as understanding the biological control will aid to prioritize candidate genes for genomic selection strategies (105). A considerable number of GWAS and transcriptome studies have been investigated and identified several candidate causal variants potentially linked with milk production and various physiological indicators of HS in dairy cattle (11, 12, 14, 15, 17-19, 24, 92-94, 96, 106, 107).…”

“…In addition, crossbreeding or backcrossing between a locally adapted Zebu breed and a high milk yielding breed (e.g., HF) to capture heterosis for heat resistance and enhance milk production in crossbreds could be an alternative or even an additional solution, while optimizing productivity still requires further investigation (2). In this context, the use of crossbreds or synthetic breeds containing some proportion of Bos-indicus genetics, such as the Girolando breed in Brazil, which is the result of crossing Gir and Holstein animals, is an alternative for managing HS in tropical areas (105). However, cumulative genetic progress can be achieved in production by combining within-breed selection with reproductive technologies (such as artificial insemination and embryo transfer) to spread elite genomes more effectively (1).…”

“…Some countries, including Puerto Rico and the United States, have already started to include the slick variant in breeding programs for Holstein (40,125), and carriers of the slick variant of Holstein bulls are already being marketed by artificial insemination companies. While the role of this variant in cold temperatures is still largely unclear, the slick mutation is also being targeted for gene editing, allowing faster introgression of the desired mutation with little to no background DNA from the donor breed (105). Remarkably, it is anticipated that genomic introgression from a highly adapted but low-production population into a highly productive but low adaptation population leads to accelerated genetic progress, perhaps, most successful when the adaptation trait is given less weighting than production traits in the selection index, potentially aiding to concurrent animal improvement (126).…”

“…In addition, investigation of the physiological systems regulated by genes involved in thermoregulation is an area that requires further study, as understanding the biological control will aid to prioritize candidate genes for genomic selection strategies ( 105 ). A considerable number of GWAS and transcriptome studies have been investigated and identified several candidate causal variants potentially linked with milk production and various physiological indicators of HS in dairy cattle ( 11 , 12 , 14 , 15 , 17–19 , 24 , 92–94 , 96 , 106 , 107 ). Recent work has shown that the SNPs rs8193046 , rs43410971 , and rs382039214 , within the TLR4 , GRM8 , and SMAD3 genes, respectively, appear to be significantly associated with 305-day milk yield, RT and RR in Holstein dairy cows kept under heat-stress condition ( 94 ).…”