Only rare classical MHC-I alleles are highly expressed in the European house sparrow

Abstract

The exceptional polymorphism observed within genes of the major histocompatibility complex (MHC), a core component of the vertebrate immune system, has long fascinated biologists. The highly polymorphic classical MHC class-I (MHC-I) genes are maintained by pathogen-mediated balancing selection (PMBS), as shown by many sites subject to positive selection, while the more monomorphic non-classical MHC-I genes show signatures of purifying selection. In line with PMBS, at any point in time, rare classical MHC alleles are more likely than common classical MHC alleles to confer a selective advantage in host-pathogen interactions. Combining genomic and expression data from the blood of wild house sparrows Passer domesticus, we found that only rare classical MHC-I alleles were highly expressed, while common classical MHC-I alleles were lowly expressed or not expressed. Moreover, highly expressed rare classical MHC-I alleles had more positively selected sites, indicating exposure to stronger PMBS, compared with lowly expressed classical alleles. As predicted, the level of expression was unrelated to allele frequency in the monomorphic non-classical MHC-I alleles. Going beyond previous studies, we offer a fine-scale view of selection on classical MHC-I genes in a wild population by revealing differences in the strength of PMBS according to allele frequency and expression level.

Keywords: adaptive immunity; immune genes; major histocompatibility complex; pathogen-mediated selection; pathogens.

Figure 1.

Relationship between MHC-I genomic allele count and allele frequency in a population of house sparrows among (a) nucleotide alleles and (b) amino acid alleles. Most genomic MHC-I alleles are rare: the number of genomic MHC-I alleles decreased rapidly as alleles increased in frequency within the population (i.e. were found in more individuals and thus more common), meaning most alleles occurred at low frequencies in the population, while few alleles were shared among many individuals. The pattern was more marked (i.e. a significantly more negative slope) for classical (orange, solid bars, solid line) alleles, compared with non-classical (blue, striped bars, dashed line) alleles, and the difference between classical and non-classical alleles was larger among amino acid alleles (b), compared with nucleotide alleles (a). Lines represent fitted means with 95% confidence intervals shown. Bars represent raw counts of unique alleles.

Figure 2.

(a) Probability and (b) level of expression of MHC-I nucleotide alleles in relation to allele frequency in house sparrows. Classical (orange, circles, solid line) MHC-I alleles were more likely to be expressed and expressed at a higher level when rare, while the probability and level of expression of non-classical (blue, triangles, dashed line) MHC-I alleles were independent of allele frequency. Lines represent fitted means with 95% confidence intervals shown. Raw values in (a) represent the proportion of birds expressing each allele, while raw values in (b) represent the mean expression level for each allele.

Figure 3.

Individual expression levels of classical (orange, circles, solid line) and non-classical (blue, triangles, dashed line) MHC-I nucleotide alleles ranked in order of decreasing expression within an individual's genotype. On average (mean ± s.e.m.), house sparrows expressed 3.21 ± 0.36 (range: 2–5) classical, and 2.37 ± 0.30 (range: 1–5) non-classical, MHC-I nucleotide alleles. Plotted values represent model-fitted means with 95% confidence intervals, back-transformed from a square-root scale and overlaid on raw data observations.