A Genomic Analysis of Chicken Cytokines and Chemokines

TLDR

Adaptive immunity evolved during vertebrate divergence, with genes under strong selective pressure leading to divergent sequences and gene family changes, making it hard to transfer mammalian immune knowledge to chickens. The chicken genome sequence offers a chance to determine which immune components are shared with mammals and which are unique evolutionary solutions. The authors performed a comparative census of cytokine and chemokine gene families by integrating chicken genome data with existing knowledge to distinguish core vertebrate molecules from lineage‑specific ones. The chicken genome contains 23 ILs, 8 type I IFNs, IFN‑γ, 1 GM‑CSF, 2 TGFs, 24 chemokines, 10 TNFSF members, and lacks lymph nodes, lymphotoxin genes, eosinophil‑related genes, and IL‑5, reflecting distinct immune architecture.

Abstract

As most mechanisms of adaptive immunity evolved during the divergence of vertebrates, the immune systems of extant vertebrates represent different successful variations on the themes initiated in their earliest common ancestors. The genes involved in elaborating these mechanisms have been subject to exceptional selective pressures in an arms race with highly adaptable pathogens, resulting in highly divergent sequences of orthologous genes and the gain and loss of members of gene families as different species find different solutions to the challenge of infection. Consequently, it has been difficult to transfer to the chicken detailed knowledge of the molecular mechanisms of the mammalian immune system and, thus, to enhance the already significant contribution of chickens toward understanding the evolution of immunity. The availability of the chicken genome sequence provides the opportunity to resolve outstanding questions concerning which molecular components of the immune system are shared between mammals and birds and which represent their unique evolutionary solutions. We have integrated genome data with existing knowledge to make a new comparative census of members of cytokine and chemokine gene families, distinguishing the core set of molecules likely to be common to all higher vertebrates from those particular to these 300 million-year-old lineages. Some differences can be explained by the different architectures of the mammalian and avian immune systems. Chickens lack lymph nodes and also the genes for the lymphotoxins and lymphotoxin receptors. The lack of functional eosinophils correlates with the absence of the eotaxin genes and our previously reported observation that interleukin- 5 (IL-5) is a pseudogene. To summarize, in the chicken genome, we can identify the genes for 23 ILs, 8 type I interferons (IFNs), IFN-γ, 1 colony-stimulating factor (GM-CSF), 2 of the 3 known transforming growth factors (TGFs), 24 chemokines (1 XCL, 14 CCL, 8 CXCL, and 1 CX3CL), and 10 tumor necrosis factor superfamily (TNFSF) members. Receptor genes present in the genome suggest the likely presence of 2 other ILs, 1 other CSF, and 2 other TNFSF members.