The evolution of avian colony stimulating factor 1 (CSF1), interleukin 34 (IL34) and CSF1 receptor genes: a functional and structural-based analysis
This project focuses on structural, evolutionary and functional analyses of the colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products in various avian species.
CSF-1 and IL-34 are the proteins involved in the control of myelopoiesis and immune response. We are cloning and sequencing these genes in various avian species in order to create a database for bioinformatic and experimental analyses of the functions of the two CSF1R ligands. We are comparing the various avian sequences and analysing the evolutionary rates of the three genes.
The biochemical properties of the proteins suggest that the selection pressure should vary among amino acid sites. Comparison of substitution rates provides an effective approach to detecting evolutionary selection. Through analysis of the ω ratios we are trying to ascertain the likely sites of positive selection in the three proteins. Simultaneously, we are working on providing a proof for the hypotheses that IL34 is a ligand crucial for development, whilst CSF1 plays a more important role during infection. We hypothesise that IL34 binds to the CSF1R with greater affinity than CSF1. Comparative analysis of avian CSF1R loci revealed likely orthologs of mammalian macrophage-specific promoters and enhancers.
Ultimately, the goal is to compare our avian data to that previously gathered in mammals.