Parasite Burden and Constitution of Major Histocompatibility Complex in the Malagasy Mouse Lemur, Microcebus Murinus

Abstract

We investigated the importance of the major histocompatibility complex (MHC) constitution on the parasite burden of free-ranging mouse lemurs (Microcebus murinus) in four littoral forest fragments in southeastern Madagascar. Fourteen different MHC class II DRB-exon 2 alleles were found in 228 individuals with high levels of sequence divergence between alleles. More nonsynonymous than synonymous substitutions in the functional important antigen recognition and binding sites indicated selection processes maintaining MHC polymorphism. Animals from the four forest fragments differed in their infection status (being infected or not), in the number of different nematode morphotypes per individual (NNI) as well as in the fecal egg counts (FEC) values. Heterozygosity in general was uncorrelated with any of these measures of infection. However, a positive relationship was found between specific alleles and parasite load. Whereas the common allele Mimu-DRB*1 was more frequently found in infected individuals and in individuals with high NNI and FEC values (high parasite load), the rare alleles Mimu-DRB*6 and 10 were more prevalent in uninfected individuals and in individuals with low NNI and FEC values (low parasite load). These three alleles associated with parasite load had unique amino acid motifs in the antigen binding sites. This distinguished them from the remaining 11 Mimu-DRB alleles. Our results support the hypothesis that MHC polymorphism in M. murinus is maintained through pathogen-driven selection acting by frequency-dependent selection. This is the first study of the association of MHC variation and parasite burden in a free-ranging primate.

Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate

“…As the parasite antigenicity changes, the relative fitness of the common host genotypes decreases and provides a selective advantage to new, rare MHC alleles to which the parasites are not yet adapted. This hypothesis is supported by both mathematical models (Takahata and Nei, 1990;Borghans et al, 2004) and several studies that showed associations between specific MHC alleles and pathogen resistance (Langefors et al, 2001;Lohm et al, 2002;Froeschke and Sommer, 2005;Harf and Sommer, 2005;Meyer-Lucht and Sommer, 2005;Schad et al, 2005).…”

“…Interestingly, also in a closely related mouse lemur species (Microcebus murinus), which lives sympatrically with C. medius in western Madagascar, the DRB locus was duplicated (Schwensow and Sommer, unpublished data). However, no evidence for a MHC-DRB gene duplication was observed in a distant southern Microcebus murinus population (Schad et al, 2005). The fact that duplication events are present in some but not all populations of a species might support the idea that under certain local conditions duplication and coexpression might be advantageous and that locally different selection pressure might affect the evolution of MHC polymorphism.…”

“…For instance, one amino-acid difference in the human DRB peptide-binding region abrogates protection to malaria (Davenport et al, 1995). Also, in Malagasy mouse lemurs (Microcebus murinus), certain amino-acid motifs in the ABS were correlated with high or low parasite burden (Schad et al, 2005). In addition, MHC supertype 7 was detected to be advantageous with respect to infection status and the intensity of infection.…”

The evolutionary ecology of the major histocompatibility complex

“…Paterson et al (1998) showed that specific MHC alleles affected both resistance and susceptibility to gastrointestinal nematodes in a natural population of Soay sheep (Ovis aries), as did Meyer-Lucht and in yellow-necked mouse (Apodemus flavicollis) and Schad et al (2005) in Malagasy mouse lemurs (Microcebus murinus). In striped mice (Rhabdomys pumilio), MHC DRB heterozygosity influenced infection status to parasites, and particular alleles occurred more frequently than expected in both high and low parasitised individuals (Froeschke and Sommer, 2005).…”

Associations between MHC genes and Puumala virus infection in Myodes glareolus are detected in wild populations, but not from experimental infection data

“…We amplified exon 2 of the MHC class II gene Drb (Drbexon2) using the 454 GS FLX (Roche) platform. We used the primers JS1 (forward; 59-GAGTGTCATTTCTACAA-CGGGACG-39) and JS2 (reverse; 59-GATCCCGTAGTTG-TGTYTGCA-39) (Schad et al, 2005). The combination of tags in the reverse and forward primers formed unique barcode identifiers and allowed the reassignation of each of the thousands of sequences obtained from the 454 pyrosequencing runs to a unique individual.…”