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
. 2020 Sep 15;20(1):119.
doi: 10.1186/s12862-020-01669-6.

Similar patterns of genetic diversity and linkage disequilibrium in Western chimpanzees (Pan troglodytes verus) and humans indicate highly conserved mechanisms of MHC molecular evolution

Christelle Vangenot  1 , José Manuel Nunes  1   2 , Gaby M Doxiadis  3 , Estella S Poloni  1   2 , Ronald E Bontrop  3 , Natasja G de Groot  3 , Alicia Sanchez-Mazas  4   5
Affiliations

Similar patterns of genetic diversity and linkage disequilibrium in Western chimpanzees (Pan troglodytes verus) and humans indicate highly conserved mechanisms of MHC molecular evolution

Christelle Vangenot et al. BMC Evol Biol. .

Abstract

Background: Many species are threatened with extinction as their population sizes decrease with changing environments or face novel pathogenic threats. A reduction of genetic diversity at major histocompatibility complex (MHC) genes may have dramatic effects on populations' survival, as these genes play a key role in adaptive immunity. This might be the case for chimpanzees, the MHC genes of which reveal signatures of an ancient selective sweep likely due to a viral epidemic that reduced their population size a few million years ago. To better assess how this past event affected MHC variation in chimpanzees compared to humans, we analysed several indexes of genetic diversity and linkage disequilibrium across seven MHC genes on four cohorts of chimpanzees and we compared them to those estimated at orthologous HLA genes in a large set of human populations.

Results: Interestingly, the analyses uncovered similar patterns of both molecular diversity and linkage disequilibrium across the seven MHC genes in chimpanzees and humans. Indeed, in both species the greatest allelic richness and heterozygosity were found at loci A, B, C and DRB1, the greatest nucleotide diversity at loci DRB1, DQA1 and DQB1, and both significant global linkage disequilibrium and the greatest proportions of haplotypes in linkage disequilibrium were observed at pairs DQA1 ~ DQB1, DQA1 ~ DRB1, DQB1 ~ DRB1 and B ~ C. Our results also showed that, despite some differences among loci, the levels of genetic diversity and linkage disequilibrium observed in contemporary chimpanzees were globally similar to those estimated in small isolated human populations, in contrast to significant differences compared to large populations.

Conclusions: We conclude, first, that highly conserved mechanisms shaped the diversity of orthologous MHC genes in chimpanzees and humans. Furthermore, our findings support the hypothesis that an ancient demographic decline affecting the chimpanzee populations - like that ascribed to a viral epidemic - exerted a substantial effect on the molecular diversity of their MHC genes, albeit not more pronounced than that experienced by HLA genes in human populations that underwent rapid genetic drift during humans' peopling history. We thus propose a model where chimpanzees' MHC genes regenerated molecular variation through recombination/gene conversion and/or balancing selection after the selective sweep.

Keywords: Balancing selection; Demographic history; HLA; Human populations; Linkage disequilibrium; MHC; Nucleotide diversity; Patr; Population bottleneck; Selective sweep; Western chimpanzees.

PubMed Disclaimer

Conflict of interest statement

The authors declare there are no competing interests.

Figures

Fig. 1
Fig. 1
Map of the human and chimpanzee MHC region showing average physical distances between the 7 loci under study in both species. The distances between loci (in Kb = kilobases) slightly vary between the two species but they have the same order of magnitude. ~ 80 Kb stands for “physical distance between DQB1 and DRB1 is about 80 Kb”
Fig. 2
Fig. 2
Genetic diversity indexes estimated in chimpanzee cohorts and human populations. Left panels: allelic richness (top), heterozygosity (middle) and nucleotide diversity (bottom) at the seven studied MHC loci in the pooled cohort of chimpanzees (in red) and averaged on multiple human populations (in blue). The pooled cohort includes all cohorts except Texascb. Middle panels: allelic richness (top), heterozygosity (middle) and nucleotide diversity (bottom) at the seven studied MHC loci in each cohort of chimpanzees (in red) and for the human populations (in blue) represented as violin plots. The values calculated for each chimpanzee cohort are indicated by filled and unfilled shapes for cohorts of wild-born and captive-born chimpanzees, respectively. The values calculated for the human populations (average number of k = 70 (s.d 15.9) samples of average size N = 109.2 (s.d 17.31)) are shown as violin plots. The width of the violin varies so as to represent the probability density of the data, the thick black bar in the centre represents the interquartile range, the thin black line extended from it represents the 95% confidence intervals, and the blue dot is the median. Right panel: allelic richness (top), heterozygosity (middle) and nucleotide diversity (bottom) at the seven studied MHC loci in each cohort of chimpanzees (in red) and for the human populations (in two shades of blue) represented as violin plots. The values calculated for each chimpanzee cohort are indicated by filled and unfilled shapes for cohorts of wild-born and captive-born chimpanzees, respectively. The values calculated for the human population are plotted as violin plots, in light blue for small sized and isolated populations that likely experienced rapid genetic drift (RGD) and in dark blue for large outbred populations with slow genetic drift (SGD).
Fig. 3
Fig. 3
Nucleotide diversity at MHC loci and other genomic regions in Western chimpanzees (A) and in different sub-species of chimpanzees and bonobos (P. paniscus) (B). R1: Non-coding autosomal regions [66]; R2: Non-coding autosomal regions [67]; R3: Xq13.3 [95]; R4: Non-coding autosomal regions [82]; R5: Mitogenome [82]; R6: Mitogenome [54]; Patr/Papa-B, C, A: average nucleotide diversity for genes Patr/Papa-B, −C, −A: this study, [61, 62]. No data is available for R1, R2 and R3 in P.t.ellioti, for R3 in P.paniscus and for R3 in P.t schweinfurthii. Values are given in Additional Table S10
Fig. 4
Fig. 4
Schematic representation of the evolutionary mechanisms explaining the genetic diversity observed in Patr genes. For each diversity index, the Patr loci are plotted according to the values given in Table 3 for the pooled cohort of chimpanzees. The pooled cohort includes all cohorts except Texascb
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Parham P. The immune system. 4th ed. New York: Garland Science; 2015.
    1. Lawlor DA, Ward FE, Ennis PD, Jackson AP, Parham P. HLA-A and B polymorphisms predate the divergence of humans and chimpanzees. Nature. 1988;335(6187):268–271. - PubMed
    1. Klein J, Bontrop RE, Dawkins RL, et al. Nomenclature for the major histocompatibility complexes of different species: a proposal. Immunogenetics. 1990;31(4):217–9. - PubMed
    1. Mayer WE, Jonker M, Klein D, Ivanyi P, van Seventer G, Klein J. Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans-species mode of evolution. EMBO J. 1988;7(9):2765–2774. - PMC - PubMed
    1. Bontrop RE, Otting N, de Groot NG, Doxiadis GG. Major histocompatibility complex class II polymorphisms in primates. Immunol Rev. 1999;167:339–350. - PubMed

Publication types