Comparative Analysis of the Chicken IFITM Locus Reveals Positive Selection and Evolution of the Locus
Irene Bassano1, Swee Hoe Ong2, Maximo Sanz-Hernandez3, Michal Vinkler4, Olivier Hanotte5, Ebele Onuigbo6, Paul Kellam1,7, Thomas Whitehead8, Mark Fife8
1Imperial College London, Department of Medicine, Division of Infectious Diseases, Wright Fleming Wing, St Mary's Campus, Norfolk Place, London, UK; 2Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK; 3Imperial College London, Department of Life Sciences, South Kensington, London UK; 4Charles University, Faculty of Science, Department of Zoology, Prague, Czech Republic; 5 International Livestock Research Institute (ILRI), Ethiopia, Addis Ababa, Ethiopia; 6Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria; 7Kymab Ltd, Babraham Research Campus, Cambridge; 8The Pirbright Institute, Woking, UK
The chicken IFITM (chIFITM) locus is clustered on chromosome 5 and contains five genes, of which three are known to be interferon stimulated genes (ISGs) with potent antiviral activity, namely chIFITM1, 2, 3. These proteins restrict viral infections by blocking fusion of the viral and host membranes, thereby interfering with viral entry and replication. Their biological activity is well documented in several animal species, but their genetic variation and biological mechanism is less well understood. Here we report the complete sequence of the IFITM locus from a wide variety of chicken breeds to examine the detailed pattern of genetic variation of the locus. We have generated chIFITM sequences from commercial breeds, indigenous chickens from Nigeria and Ethiopia, European breeds and inbred chicken lines from The Pirbright Institute, totalling of 211 chickens. Our data reveal that the chIFITM locus does not show structural variation across the populations analysed. However, SNPs in functionally important regions of the proteins were detected, in particular the European breeds and indigenous birds from Ethiopia and Nigeria, revealing some SNPs were simultaneously under positive selection. Together these data suggest that IFITM genetic variation may contribute to the capacities of different chicken populations to resist virus infection.
This research was supported by the BBSRC (Animal Health Research Club) grant Number BB/L003996/1 and BBSRC grant BBS/OS/GC/000015/2.
Keywords: variant calling, SNPs, INDELs, GATK, positive selection