Comparative Evolutionary and Structural Analysis of the Avian and Mammalian CSF1R systems

General: the dataset contain sequence data, analysis pipelines and result files, which includes supporting the thesis of Maria Weronika Gutowska available from https://www.era.lib.ed.ac.uk/handle/1842/15852
Details:
The folders contains files for the following project works:

- Gallus gallus BAC library and BAC clones containing CSF1 gene region, including the genome sequence covering the gene and promoter region of the gene.
- Comparative data to support comparative analysis of the CSF1 gene in mulitple bird species
- Modelling data of the CSF1 gene structure
- Gene tree and gene family data and alanalyses

The primary objective of this thesis was the comparative functional and structural analyses of the three proteins in birds and mammals, using evolutionary and experimental approaches. Here the presence of CSF1, CSF1R and IL34 genes and protein products is identified in anumber of evolutionary diverse birds, indicating that the system is well maintained within the group.
Avian genes were cloned and sequenced or otherwise extracted from different databases, and the mammalian sequences were gathered from available online sources. Whilst the gene regulation and the differential expression of the mammalian CSF1R, CSF1 and IL34 are reasonably well understood, they have not been extensively studied in birds. Preliminary comparison between these two groups provided in this thesis suggests a number of similar patterns are involved in regulation of avian CSF1R system.

The mammalian CSF1/CSF1R and IL34/CSF1R ligand:receptor peptide interface has been previously resolved and was used to model similar structures in the chicken. The models were then utilised to determine which amino acids are involved in receptor binding in birds.
The apparent lack of cross-species reactivity between the chicken CSF1 and zebra finchCSF1R provided a basis for an experimental validation of the in silico binding site predictions. Altogether the structural modelling, evolutionary analysis and experimental confirmation provided sufficient proof for the location of avian CSF1/CSF1R interface.
Finally, an extensive bioinformatics analysis has been performed on both the coding DNA and the protein structures of the CSF1R system. The results uniformly showed that IL34 remains under purifying selection in both groups. CSF1 is diverse amongst most mammalian species, while avian CSF1 is only positively selected along particular lineages. This implies the rapid evolution of mammalian CSF1, probably in response to the selection pressure from
pathogens. Contrasting situation is found in the CSF1R. Whilst mammalian CSF1R remains positively selected only along particular branches, avian CSF1R presents a number of pervasively positively selected sites, found mostly in the extracellular domains of the receptor. That suggests that in birds it is the receptor, not CSF1, which remains under strong selective pressure. These indicates that birds employ a unique way of competing in the hostpathogen
arms race, suggesting the existence of yet unknown pathogen-encoded protein interacting with the avian receptor.