Disease Susceptibility Associated with Genetic Variation of the Major Histocompatibility Complex (MHC) and Population Structure in African Elephants
Background

The large, poaching-related decline in African elephants, coupled with loss of habitat, has resulted in smaller, more isolated elephant populations throughout sub-Saharan Africa .  Indeed, only 16% of African elephant habitat is considered protected in the form of parks, game reserves and management areas.   In unprotected areas, range contractions have continued due to agricultural needs of expanding human populations, placing human-elephant conflicts at an all time high.

The above changes have significantly restricted gene flow between isolated elephant populations.  This, coupled with increased interactions between elephants, humans and their domesticated animals, may already have become a ticking time-bomb, making currently marginalized elephant populations fatally susceptible to disease epidemics.

The major histocompatibility complex (MHC) is a cluster of genes that code for immune response as well as the presentation of foreign antigens (e.g., pathogens) to killer T cells for destruction.  These genes have been shown to be highly polymorphic in many species where they have been examined, and this variation has been demonstrated to be crucial for effective immune responses to diseases.  
Figure 1:  A cell presenting a MHC molecule to a T-cell to initiate the immune response.(Ploegh lab, Harvard Medical Center)
Objective

We are developing noninvasive genetic methods to measure the level of MHC variation in African Elephants and comparing this variation among populations that have experienced various levels of habitat fragmentation, population decline and isolation.  Our hope is that such variation observed at the population level will indicate the extent of past pathogen-host interactions for this species and will help to identify populations currently at greatest risk of future disease outbreaks.

Specifically, we are developing new techniques that can be used to sequence MHC-coding DNA in elephant fecal samples.  These data complement the genetic data obtained from our ivory tracking project, which uses population differences in neutrally selected microsatellite DNA to determine the origin of ivory samples.  Population differences reflected by neutral DNA arise solely from migration, isolation and random genetic drift.  By contrast, population differences in MHC DNA are most strongly the products of natural selection.  By comparing population differences based on neutral (microsatellite) versus selected (MHC) DNA, we hope to identify populations most heavily subjected to past pathogen-host interactions, along with their associated population characteristics (e.g., populations in areas of high biodiversity where pathogens are also more diverse, coupled with recent isolation).  This should, in turn help us predict the populations that are currently at greatest risk of disease outbreaks, as well as land management techniques that show the greatest promise at reducing such risk.
Figure 2: African Elephant DNA (Fronicke et al. Pro. R. Soc.  Lond.  270, 1331-1340 2003)
Acknowledgments

This work is supported by the Center for Conservation Biology and the providing of study samples by Association of Zoos and Aquariums (AZA) Elephant advisory group, and the Woodland Park Zoo.
For Further Information
Siri Nelson, Graduate Student