Linking habitat fragmentation and disease: the major histocompatibility complex class II and its role in disease of the koala (Phascolartos cinereus)

A project undertaken at the University of Sydney and supervised by Damien Higgins

This project arises from a need to understand mechanisms by which genetic change associated with habitat loss and fragmentation and a history of hunting and translocation predispose marsupials to disease.  Due largely to habitat destruction and translocation, koala populations are highly fragmented and, in some cases, highly inbred (1).  Inbreeding might affect the fitness of the immune system of the koala by reducing diversity at the Major Histocompatibility Complex (MHC). MHC genes encode a family of proteins involved in recognition of disease-causing organisms (pathogens). The diversity of MHC genes allows individuals and populations to recognize and respond to a wide range of pathogens.  MHCII-dependent pathways are likely to be essential to the control of the two most common infectious diseases of the koala: chlamydiosis and cryptococcosis.  The high prevalence of these diseases in some koala populations (especially those in fragmented habitat) (2,3), have long suggested that MHC Class II function plays an important role in the susceptibility of koalas to these diseases.

This project brings together for the first time susceptibility of koalas to disease (primarily Chlamydiosis and Cryptococcosis), habitat fragmentation and inbreeding via the central and measurable link of the immune system.  This makes it highly significant on several levels.  Firstly, it provides important information on the impact of genotype, gene flow and habitat fragmentation on the koala immune system and, therefore on the viability and welfare of koala populations.  This has application in planning and development on local and national scales. Secondly, this study creates a foundation for studies investigating the impact of other anthropogenic factors on the immune system, and therefore health and welfare of wild animal populations.  Thirdly, on a national and international scale, this will contribute to our understanding of, and our capacity to study, the immune function of our wildlife species, which is important in the control or emergence of new and introduced diseases.

Aims
  1. Further characterize koala MHCII genes
  2. Develop and validate methods to assess immune function of the koala (these would also be applicable to other marsupial species).
  3. Use these, and other methods to test the hypotheses that MHCII-related factors can impair the immune system of the koala.
  4. Create a foundation for other studies examining the impact of inbreeding and other anthropogenic factors on disease susceptibility of a wide range of native animal species.
References
  1. Houlden BA, Greville, WD, Sherwin WB (1996) Evolution of MHC Class I loci in marsupials: characterisation of sequences from koala (Phascolarctos cinereus). Mol. Biol. Evol., 13, 1119-1127
  2. Ellis, W.A., Girjes, A.A., Carrick, F.N. and Melzer, A. (1993) Chlamydial infection in koalas under relatively little alienation pressure. Australian Veterinary Journal 70, 427-8.
  3. Jackson, M., White, N., Giffard, P. and Timms, P. (1999) Epizootiology of Chlamydia infections in two free-range koala populations. Veterinary Microbiology 65, 255-64.
 Publications Resulting from the Project

Lau, Q., Griffith, J., Higgins, D. (2014). Identification of MHC11 varients associated with chlamydial disease in the koala (Phascolarctos cinereus). PeerJ, 2, 1-14.

Lau, Q., Jaratlerdsiri, W., Griffith, J., Gongora, J., Higgins, D. (2014). MHC class 11 diversity of koala (Phascolarctos cinereus) populations across their range. Heredity, 113, 287-296 (also selected for Heredity podcast)

Lau, Q., Jobbins, S., Belov, K., Higgins, D. (2013). Characterisation of four major histocompatibility complex class II genes of the koala (Phascolarctos cinereus). Immunogenetics, 65, 37-46

Lau, Q., Canfield, P., Higgins, D. (2012). Expression and in vitro upregulation of MHCII in koala lymphocytes. Veterinary Immunology and Immunopathology, 147(1-2), 35-43.

Jobbins, S., Sanderson, C., Griffith, J., Krockenberger, M., Belov, K., Higgins, D. (2012). Diversity of MHC class II DAB1 in the koala (Phascolarctos cinereus). Australian Journal of Zoology, 60(1), 1-9.

Additional papers from our lab, arising from Dr Lau's expertise:

Maher, I., Griffith, J., Lau, Q., Reeves, T., Higgins, D. (2014). Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus) by qRT-PCR. PeerJ, 2013 (1), 1-19.

Lau Q, Wilkin T, Payne E, Gray R, Gongora J, Higgins DP (2014) Primers for amplifying major histocompatibility complex class II DQB and DRB exon 2 in the Australian sea lion (Neophoca cinerea) Conservation Genetics Resources (Impact Factor: 1.14). 12/2014; 6(4). DOI: 10.1007/s12686-014-0244-2

Lau Q, Chow N, Gray R Gongora J, Higgins DP. MHC class II DQB and DRB diversity in pups from two major Australian sea lion (Neophoca cinerea) colonies. In review at Heredity

 

Koala (Phascolartos cinereus)