Interacting gene clusters and the evolution of the vertebrate immune system

Unraveling the "code" of genome structure is an important goal of genomics research. Colocalization of genes in eukaryotic genomes may facilitate preservation of favorable allele combinations between epistasic loci or coregulation of functionally related genes. However, the presence of interacting gene clusters in the human genome has remained unclear. We systematically searched the human genome for evidence of closely linked genes whose protein products interact. We find 83 pairs of interacting genes that are located within 1 Mbp in the human genome or 37 if we exclude hub proteins. This number of interacting gene clusters is significantly more than expected by chance and is not the result of tandem duplications. Furthermore, we find that these clusters are significantly more conserved across vertebrate (but not chordate) genomes than other pairs of genes located within 1 Mbp in the human genome. In many cases, the genes are both present but not clustered in older vertebrate lineages. These results suggest gene cluster creation along the human lineage. These clusters are not enriched for housekeeping genes, but we find a significant contribution from genes involved in "response to stimulus." Many of these genes are involved in the immune response, including, but not limited to, known clusters such as the major histocompatibility complex. That these clusters were formed contemporaneously with the origin of adaptive immunity within the vertebrate lineage suggests that novel evolutionary and regulatory constraints were associated with the operation of the immune system.     

Cis-regulatory properties of medaka synexpression groups

During embryogenesis, tissue specification is triggered by the expression of a unique combination of developmental genes and their expression in time and space is crucial for successful development. Synexpression groups are batteries of spatiotemporally co-expressed genes that act in shared biological processes through their coordinated expression. Although several synexpression groups have been described in numerous vertebrate species, the regulatory mechanisms that orchestrate their common complex expression pattern remain to be elucidated. Here we performed a pilot screen on 560 genes of the vertebrate model system medaka (Oryzias latipes) to systematically identify synexpression groups and investigate their regulatory properties by searching for common regulatory cues. We find that synexpression groups share DNA motifs that are arranged in various combinations into cis-regulatory modules that drive co-expression. In contrast to previous assumptions that these genes are located randomly in the genome, we discovered that genes belonging to the same synexpression group frequently occur in synexpression clusters in the genome. This work presents a first repertoire of synexpression group common signatures, a resource that will contribute to deciphering developmental gene regulatory networks.     

Exploring the molecular mechanism of acute heat stress exposure in broiler chickens using gene expression profiling

The process of heat regulation is complex and its exact molecular mechanism is not fully understood. In this study, to investigate the global gene regulation response to acute heat exposure, gene microarrays were exploited to analyze the effects of heat stress on three tissues (brain, liver, leg muscle) of the yellow broiler chicken (Gallus gallus). We detected 166 differentially expressed genes (DEGs) in the brain, 219 in the leg muscle and 317 in the liver. Six of these genes were differentially expressed in all three tissues and were validated by qRT-PCR, and included heat shock protein genes (HSPH1, HSP25), apoptosis-related genes (RB1CC1, BAG3), a cell proliferation and differentiation-related gene (ID1) and the hunger and energy metabolism related gene (PDK). All these genes might be important factors in chickens suffering from heat stress. We constructed gene co-expression networks using the DEGs of the brain, leg muscle and liver and two, four and two gene co-expression modules were identified in these tissues, respectively. Functional enrichment of these gene modules revealed that various functional clusters were related to the effects of heat stress, including those for cytoskeleton, extracellular space, ion binding and energy metabolism. We concluded that these genes and functional clusters might be important factors in chickens under acute heat stress. Further in-depth research on the newly discovered heat-related genes and functional clusters is required to fully understand their molecular functions in thermoregulation.