Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr 6;22(1):42.
doi: 10.1186/s12862-022-01998-8.

Selection and demography drive range-wide patterns of MHC-DRB variation in mule deer

Rachel M Cook  1 , Brittany Suttner  2   3 , Rachael M Giglio  2   4 , Margaret L Haines  2   5 , Emily K Latch  2
Affiliations

Selection and demography drive range-wide patterns of MHC-DRB variation in mule deer

Rachel M Cook et al. BMC Ecol Evol. .

Abstract

Background: Standing genetic variation is important especially in immune response-related genes because of threats to wild populations like the emergence of novel pathogens. Genetic variation at the major histocompatibility complex (MHC), which is crucial in activating the adaptive immune response, is influenced by both natural selection and historical population demography, and their relative roles can be difficult to disentangle. To provide insight into the influences of natural selection and demography on MHC evolution in large populations, we analyzed geographic patterns of variation at the MHC class II DRB exon 2 locus in mule deer (Odocoileus hemionus) using sequence data collected across their entire broad range.

Results: We identified 31 new MHC-DRB alleles which were phylogenetically similar to other cervid MHC alleles, and one allele that was shared with white-tailed deer (Odocoileus virginianus). We found evidence for selection on the MHC including high dN/dS ratios, positive neutrality tests, deviations from Hardy-Weinberg Equilibrium (HWE) and a stronger pattern of isolation-by-distance (IBD) than expected under neutrality. Historical demography also shaped variation at the MHC, as indicated by similar spatial patterns of variation between MHC and microsatellite loci and a lack of association between genetic variation at either locus type and environmental variables.

Conclusions: Our results show that both natural selection and historical demography are important drivers in the evolution of the MHC in mule deer and work together to shape functional variation and the evolution of the adaptive immune response in large, well-connected populations.

Keywords: Adaptation; Cervidae; Genetic drift; Genetic variation; Historical demography; Major histocompatibility complex; Microsatellites; Natural selection; Next-generation sequencing; Parasite-mediated selection.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Maximum likelihood phylogenetic tree of MHC DRB exon 2 allele sequences. Sequences included here are the 31 new mule deer alleles (Odhe, Odocoileus hemionus) shown by blue circles, 30 white-tailed deer alleles (Odvi, Odocoileus virginianus) shown by red squares, and outgroups including moose (Alal, Alces alces; green triangles), roe deer (Caca, Capreolus capreolus; purple diamonds), elk (Ceel, Cervus elaphus; orange stars), sika deer (Ceni, Cervus nippon; navy crosses), and caribou (Rata, Rangier tarandus; yellow pentagons), rooted with an orthologous cattle DRB sequence (Bola, Bos taurus). Nodes are labeled with bootstrap support values. The shared allele between mule deer and white-tailed deer (Odvi-DRB*09) is shown with a red arrow
Fig. 2
Fig. 2
Sampling sites and MHC allele frequencies. 24 individuals were sampled from each of 16 sites spanning the range of mule deer (shown in light grey) between 1995 and 2005. The orange circles show the location of the sampling sites. Site details can be found in Additional file 2. The pie charts represent the proportion of different MHC alleles found in each population, with each allele’s respective color shown in the legend chart (1 = Odhe-DRB*01). The top 10 most common alleles are labeled in the legend with asterisks. Only the most common allele, Odhe-DRB*01, shown in the lightest blue, was found in every population. The shared allele between mule deer and white-tailed deer, Odvi-DRB*09, is shown in the darkest brown
Fig. 3
Fig. 3
Cluster analysis using Discriminant Analysis of Principal Components (DAPC). Scatterplots show the DAPC of genotypes from the 16 mule deer populations at (a) the microsatellite loci and (b) the MHC locus. Each individual is represented as a point, colored based on its population of origin, with red being southern or low latitudes and blue being northern or high latitudes. Populations are surrounded by 95% inertia ellipses
Fig. 4
Fig. 4
Variation in amino acids for MHC class II DRB exon 2. Amino acid sites corresponding to human HLA-DRB antigen binding sites are shown in red. Positively selected sites using PAML model M8 are denoted by asterisks (*p < 0.05 and **p < 0.01)
Fig. 5
Fig. 5
Isolation by distance. The genetic distance (Jost’s D) between each pair of populations was calculated for microsatellites (blue triangles) and MHC (green circles) and compared to geographic distance
Fig. 6
Fig. 6
Mean-centered allelic richness and latitude. Mean-centered allelic richness is similar across latitudes for both MHC (green circles, dashed line) and for microsatellites (averaged across loci; blue triangles, solid line)
Fig. 7
Fig. 7
Redundancy Analysis (RDA) for microsatellites and MHC. (a) Axes 1 and 2, explaining 46% and 23% of the variance, respectively, in allelic richness for 9 microsatellite loci across 16 populations. (b) Axes 1 and 2, explaining 27% and 21% of the variance in allele frequencies for the MHC locus across 16 populations. Points for each plot are colored by population according to latitude. Vectors in blue show constraining axes, or environmental predictors, pointing in the direction of positive contribution, including latitude (Lat), longitude (long), elevation (elev), mean annual temperature (MAT), mean annual precipitation (MAP), temperature difference between warmest and coldest months (TD), and relative humidity (RH)
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Barrett R, Schluter D. Adaptation from standing genetic variation. Trends Ecol Evol. 2008;23(1):38–44. - PubMed
    1. Lai Y, Yeung C, Omland K, Pang E, Hao Y, Liao B, Cao H, Zhang B, Yeh C, Hung C, Hung H, Yang M, Liang W, Hsu Y, Yao C, Dong L, Lin K, Li S. Standing genetic variation as the predominant source for adaptation of a songbird. Proc Natl Acad Sci USA. 2019;116(6):2152–2157. - PMC - PubMed
    1. Przeworski M, Coop G, Wall JD. The signature of positive selection on standing genetic variation. Evolution. 2005;59:2312–2323. - PubMed
    1. Fisher MC, Garner TWJ, Walker SF. Global emergence of Batrachochytrium dendrobatidis and amphibian chytridiomycosis in space, time, and host. Annu Rev Microbiol. 2009;63:291–310. - PubMed
    1. Van Rooij P, Martel A, Haesebrouck F, Pasmans F. Amphibian chytridiomycosis: a review with focus on fungus-host interactions. Vet Res. 2015;46:137. - PMC - PubMed

Publication types

LinkOut - more resources