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Mating preferences can drive expansion or contraction of MHC gene family

February 2020
Proceedings of the Royal Society B: Biological Sciences 287(1921)

DOI:10.1098/rspb.2019.2706

Project: Evolution of the number of copies of MHC genes: testing optimality hypothesis and exploring alternatives

Authors:

Piotr Bentkowski

University of Warsaw

Jacek Radwan

Adam Mickiewicz University

MHC-based mating rules can evolve as a way to avoid inbreeding or to increase offspring immune competence. While the role of mating preference in the MHC diversity in vertebrates has been acknowledged, its impact on individual MHC diversity has not been considered. Here, we use computer simulations to investigate how simple mating rules favouring MHC-dissimilar partners affect the evolution of the number of MHC variants in individual genomes, accompanying selection for resistance to parasites. We showed that the effect of such preferences could sometimes be dramatic. If preferences are aimed at avoiding identical alleles, the equilibrium number of MHC alleles is much smaller than under random mating. However, if the mating rule minimises the ratio of shared to different alleles in partners, MHC number is higher than under random mating. Additionally, our simulations revealed that a negative correlation between the numbers of MHC variants in mated individuals can arise from simple rules of MHC-disassortative mating. Our results reveal unexpected potential of MHC-based mating preferences to drive MHC gene family expansions or contractions and highlight the need to study the mechanistic basis of such preferences, which is currently poorly understood.

Mating preference rules tested in simulations. Scenarios marked with the asterisk are only presented in the supplementary materials. The intrinsic cost of expressing too many MHC variants were modelled as explained in SM1 (eq.2 p.3 in SM1).

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Parameters of the model. 1 total number of pathogen individuals was equal to Np· S; 2 probability per reproduction event; 3 probability per site (flip of a single bit); 4 probability of change of the whole MHC (change in any given site); 5 used not in all scenarios.

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

!!!"#!#$%&'(

&Bentkowski P, Radwan J. 2020 Mating preferences can drive expansion or contraction of major

histocompatibility complex gene family. Proc. R. Soc. B 20192706. http://dx.doi.org/10.1098/rspb.2019.2706

Mating preferences can drive expansion or contraction of MHC gene family

Piotr Bentkowski, Jacek Radwan 

 !"#$%#&

!'()*                    *        +

,---!'(*-

*"!'(-*'

          -          !'()

  +  -      -  *    !'(        

            ,  -  -  -  +    -

*.

-/**!'(--'

-  -  - + !'( *

--  -                -    

 *- * !'(   

    !'()    0      1      !'()*

!'(1----

--*---

Introduction

2- -*1!'(- 

   - *

-

3)4!'( *

*--

 -

-  2)   5    !'()  1  

*   %- 

 * 

-2-

--

--  -    !'(        -#

6 )/)

7)8!'(       



 3  9  %    !'()  

9:

-!'(-;)33

,--  !'(- - *

1    *  - 8  3<)38  -

      -  *    !'(  

1* -

* 39  !'(*  *

+3:)<=-

1"!'(-**

*    +      -    -

+- 

-#   !'(   -*  

!'(    1        *  

-7 <3  -

     --  * <<<4

'-1!'(" *

*----

--  - !'(

 )  -  <7

<>    --  -          

  *  -            

 <8)<:              -

* !'(   -   

    -" <;  - 4=  # 

43*<3.

*--"+-*!'(

 +*1 * -

+-*

-          --        -

*+!'(*39'

-- !'(

-!'(

%!'()  

  - -

"               

3 92- 51 -

- --

1 5* 

*4<!'(

"    "- 44 )  -  1  -

-  -    

2---!'(

+-*2-

1--!'(

--

 2) !'( -#-* * 

*--#

- 

       7  .  /

    !'(      -    

---*5

*-*-1

!'(    - --  !'( )

*

.    -     

!'(      

  * 1   47 4> 5-

4849  4: * 4; - 7= *

--737<74!)

-)-77)

- * : - -   

)5'

*-    *      +  #

  -  -    )5  ?-

+    +  #  *  16  

  +        

5 !'( -  

5  +      !'(   

1-!'()*  

        5    !'(  

**@

    (  1    !'(

-"--

----5

 *'   

  -        !'()

   +-  !'(

.-

!'()* - 

!'(1!'()*

 --   1 )

5!'(

Methods

,  !'()*   

--!'(**

A

2-)

  -  "        

  -  -      * -

*----1

        -  !'(      *

39  *              -  2-

  "        !'()-  )

    *      -      

- -   !'( 8;

34  .    !'(    *        

        =   3  *    %-

    *    -      *  /

*--@!'(--@

 -      ?

!3

. * - 5 -  - 

*-*""

B39!'(38*)

-  *  *--      *

-!'(C-3<D<4-

  -  !'(    7>  -  -  -  

--*!'(*

      !  -  

* !'(  

--*

-    -  +  *      0

    * *  -!'(



%-@      8===  *)  .  -

  -        38)*)  *)  

---@!'(-*

----

-*-*-

?" 39

1--!'(

?!3   --A  -

-        2)        

<7<>

2---5-

" !'()   -.

-**-

*-"+

*1-/)

--  2-        

-  - + 3= 

---

    *  *  2-      

+B--

3===

,          --

- --**

-"2-5---

 * !'(----

!?---?-*

+     -  

        -  

**  *  '  -   

-E5-

-              

 2-  

--+

-    -        +    +

  2-    --  %?-    -

-min(|A∩B|/|A∪B|- 

   

 - 

---*!'(

  +    -    *  -  -

!1F+ .   B   

-

2!'(

1  -*     1

!'(

!?-$  !?- * *

   1   !'( 

*   -*   

-%?-$  %?-*

  2-      /    

--

        ?3     

*-2*3

Table 1: Mating preference rules tested in simulations. Scenarios

marked with the asterisk are only presented in the supplementary

materials. The intrinsic cost of expressing too many MHC variants

were modelled as explained in SM1 (eq.2 p.3 in SM1).

Abbrev. Brief description

Number of

mates to chose

from

MinShared

Preference for mates with the

smallest number of identical

MHC variants

PropShared

Preference for mates with

minimal proportion of shared

identical MHC variants within the

sum of variants in both partners

Random No preference, random matching

of mates N/A

MaxDiffer

Preference for mates with the

largest number of MHC variants

different from the chooser

MinSharedUnc*

Preference for mates with the

smallest number of identical

MHC variants

PropSharedUnc*

Preference for mates minimising

proportion of identical MHC

variants among the sum of

variants in both partners

-+-

!'(*39--

Fig."1 )*$%&+"""",$-./"",0-.*

/"1""*),$12)./"*3$%&

/""",4"."!"!,*

"+556+5.*,7/

*.81!"3*"*- *!*"

(1!-+-9

*        -      3=)>

>G3=)>  *    -  

-7:38-

#         *      -

-      -

-    +    * /  

+    --    39  2-

  *      -      -

*!'(- 

*  C  *

38    *1  !'(

  *      *  2-

2*<

Table 2: Parameters of the model. 1 total number of pathogen

individuals was equal to Np· S; 2 probability per reproduction event;

3 probability per site (flip of a single bit); 4 probability of change of

the whole MHC (change in any given site); 5 used not in all

scenarios.

Parameter description Symbol Values

Hosts population size (number of individuals) NH1000

Pathogen population size of a species (number of

individuals) 1NP1000

Number of pathogen species in the simulation S4, 8, 16

Antigen length (number of bits) a6000

MHC’s antigen-binding region length (number of bits) m16

Number of pathogens generation per one hosts

generation K10

Total number of hosts generation (a.k.a. simulation

time) G5000

Probability of mutation in antigen (per site) 2,3 μA

10-5 ,

5 · 10-5

Probability of mutation in MHC PBR (per protein) 2,4 μMHC 10-4

Probability of deletion of MHC gene 2μdel 10-3

Probability of duplication of MHC gene 2μdupl 10-3

Cost factor for the host selection function 5α0.02

Number of random partners to select from in sexual

selection P10

-3<>=

-----))

*-*!'(

  *-        1    

  -            !'(  

* *-  -

  -   *    /  !'(    

*--.HI * *

5

-" -  3<>=  - 

? -  -

    .HI        *    -

      -      51  

?B47<78

- 1-- -

  )  - 

- * !'( 2- *

+.HI-

  .HI    -  )  *  )  -

   -   -.HI

-      ?*/    -  -

  -  "  .HI     -  +

* .HI-

.HI  ,    -  *    -  *   !'(

    -  -      -    3<>=

              *

JK  HI        JL=  B  

-      -  J    HI    

*-.HI51

 2-- * -* 

- .HIA # 

<

Results

.  !'()*    -  

5 +-*  

.HI 3-- A -*  

-?<2-+

-  -  *    -  !'()*  

2---

"        -  -      !?-

   !'( 1 3 

-      -          

* ?32- -)

*-

Fig."2 !"*$%&,:;.*

"**",<=:;.$%&+",

=/""/*!*".!",*+5>56+5.

?

√

/!=="**:;%/!

"!*,7.-7-5

-*-

*  -  +    -      *    .HI    -

B  2*?4   

    39  !?-  -  "  .HI

  -        3  $

%?--.HI

  B      3  1      

*-----

      A      5  -)

  2*  ?7      2-

.HI

    !1F+      3  2*  ?>

  H*  !'(  

A .HI   ?4

    ,  1  --  

 - !'( 

.HI*,-

-- -@.HI

  -     .HI      

-  .HI    -  -      <  2*  ?8)?:

.!?--

5  .HI  M  

-  -    *  5      

-   -!?- 2*

?9!1F+-

-    5  )  2*  ?:



Discussion

2--!'()

5+-

!'(-   -  

  *    ;  33  '    -  -  !'(

*    -  -        

/    -      -  *    !'(

-

'-  - +   -

 -  .-

-    *        -  

!?--1-!'(

          B"*    

    !'(        

-*-

-    !'(    1  2-

      +  -   -    

-  %?-  

- - -

* **-

+  $-- !'(

    -    /  *  5    

-5

(/    %?-      

-  !'(  1        

  -  *-    /     

!'(    1    *  0    -

  -  +    -    !'()*

*")5

!'(

<;79#<37:

F*-/

 - !'(* - 

*    -      -

      -        

1"B--

*      !'(        

-    4>  -  *      --  

+7;-->=*

, -   - -

  1    2-      

-**

---* 1-*

      !'()    

--  -  *  - *-

  -  -  !  5-    -  

!'(-!'(

--->3

    -  -      -  -  *  

    -        

?"    -    !'(    -

  "*"        ><

'*"  

    -    *  *    !'(    

 -!'(    

-*1

")*--

*-!'()

*-**

1    - 

-4;7;

.    -    !'()*

-

 *   -- 

--1

-!'(-*

        -        

 --  * 

    - * 

1  *    +        --

*   - -*!'()*

- 3' 1--

    *    !'(       

      *  -  *  *5  

*)-*"*

-      *    --      *  

4<,-"5

*            -  -

-*

      !'()*    

            +

**"*

   -           

-

!)  :  >7  ---  -  

---!'(

-#      )      

1--!'( 

- -    !?-   

---!'(*

        *     !'(

*

  ,  -     -      -

*-- -

*!'(-N

-    "     *        -

+-1!'(

          -   !

-    -        -    -

  *    !'(    ><  >7      *

1  '  -      -  

-1+

-  -    *    !'(      

--**

2--!'(-+.HI

 H-*   1

  --    -        

  .  -  1      -  -    

---

    

-!'(*+.

-        O  P  

-*----

-- *  )>> >8 ' 

 - -  

  -   !'( 2-

  -  *  1  -      O

P*!'()*

            -

  F  *      

-*-

1  -  -    "    -

!'(   ><$ -  1

-

 - 1 * !"

><-**)

  ** - -

*--

(      -  -  

    !'(    -  -  5

/    -      !'(    

1    *    F+   5

-"+

  --   1)5

+   -  *    !'(     F

  -     -

-              

 *  -

  -    -  

-!'()*

Data accessibility

2-        -      *    

-66-*6*""6!'(Q 2-  

      -  F  F  B

-6663=>=8366>9

Acknowledgements

, -"  2 *  R# S  ,#    

          -    

-

Founding

2-  -      *  %-  H  ?

( $!0)473  <=346=:6 6HT:6==3>4    

SB(-%#&?

H"(%(??

Authors' contributions

SB - --

        -      

-  C %     -

-@

---5

**-*-"

-

References

1. !"  !  <==8  2-    -*  1

1        -   B    

?493>;)3:8

2. I%F? %B B+RB U%,V3;;92-

--*1(

B.39<39;)<<7

3. ?  R U  B-  F?  <=3=  '  -  

    !'(  -    

%    -  B  ?  )  ?

<9938:7;9;);::

4. %  FS  F-  V  U  %  ,V  <==<  !'(

-#            )

%-H ?

-$? ;;3933<8=)33<87

5. %-  V%     <=3:  .     

 -D- %

-H ?33>93>><)3>>9

6. !SUBS <=3> BW  

      !  '*  (1  !'(

%R?(33333==78<9)3==78<9

7. %  FS <==<  2-        *  ?1

    -    -*  1  -

3=:33)<3

8. V20XFV,-'? UH"?

<=37 /!'()*-

     !  <4<3>3>3)

>384

9.  !SBSU, <=37 ?1

  -        -  !  '*

(1%B?R<:3<=37388<

10. ,# S(   <=34 ?1  1 

      -      -*

1  -    %    -  B  ?  )

?<:=398;<=3438=>

11. '"%,3;;<- -

-*134<>9>)>:3

12. 2"-  H  U  H  !  3;;=      

    /)    

- ! '*(1  

3<77;89);9:

13. -  S !    S  U  F    BS  <==7  !'(

- -)- .

>>3394<)94;

14. FBS-S !!V(U,

S<==7'#1 ---

--!'(.>>339<>)943

15.  0- ( <==;  -   !'(

* -%- B

?)?<9838>98>9)88>

16. '"%,<==<%-

!'(>83=3;=<)3;=:

17. ""  %  U  B  S  <=3;      

-*1*%R0?(

3>>3==9=3>

18. V,!3;;7B')!.5

%('%2)3889

%S.3><:4;=7)4;3<

19. %? <=34 'R (.     -

%)  B    F+  ?#  E  

.S.3;33<>:43)>:4;

20. R# 2R <=33 (   !'(..)

*           1 )

-8>:<4:=)<4;=

21. #"   <=3:   - 1

  -*  1        

!<933<>;7)<8=4

22. 0X(     (  (V  '/  F  H  S   U

,- '  <=3:  2-           

#  H  U  <>:73)

:7;

23. !  %  %"    F  %0  U  ,--  R  <=3:

(H*-!'(I- 2

R33339)<:

24. H"! 2#)'-VU S!3;;<2-

*      -*  1      

%-H ?-

$? :;<<3=:;8)3=:;;

25. !"  !  ?*    U  B  S  <=3;  !

-*1.-2

    %    -  H    

?<=3:=9:87

26. ,V!V*!V#SB-2'U!"!<==4

%          ?

4=3>84:3474)3474

27. V- *", ?"UBS<=3=+

 !'()FB   *  -   

    - *"    !    !  

3;<>>)<8>

28. !2U$ <==8!'(. 

-  -S

3;83;94)3;9:

29. V S I"' U , 'S 3;;> !))

!-      $#)!-  )  <  1    ?  

%-.B37484)::

30. "  ?  U  2  S  <===  2-  -  

-*  1  R    -  FH  /

B'3339)349

31 !"!  ?*  V#!  V" %  UB  S

<=39F*-

  )      !'(    .    -  *"  

!'33:747:)4>9

32 (""% U B+F 3;;; .*   -

':4<8=)<9=

33  SR U " 3;;7V.HB(0H.2.0H HF2'

! S0B '.?20(0!% 2..R.2N(0!%RY) H.H2B 2.IBI.,

H374474>)783

34 N#"  V    3;98(   

  *      ! ' *  (1  S  

1!377>34<7)344>

35 BS2"# UV- <==:!'(

-*"-337;:<9):44

36 * !B- !  S U ?- (<=3=

! -    *5  - !'(

    -   *  B-    

87838:4)38;8

37 - ??!U, <=3<!

-    -  *  -  '  *

-<47:8;):9:

38 0!<==4!-*1

 -  # % -B? 

R?)?<9=?<>7)?<>8

39 -!     <==;  (  !'()

              

%    -  B  ?  )  ?

<9838>;3=:4)3=;<

40 ,"(?*"2U%" S3;;>!'()

-% - B

?R?)?<8=34>;<7>)<7;

41 % ? U%* S! 3;;9 H   

-*  1)         )

      %    -  B  ?  

R?)?<8734:;3:34)3:3;

42  F' , BH "FTUFS

<==;  ()    -      

!'()!

3:3>44=9)443>

43 ,-' <==7 H   !'()* 

          *  !  

34:<78>)<79=

44 ,#S(<=3>+-#!'(

        1)      -  

    5-  -    

?*8;47>;)78;

45 ?RS 3;;7(--..

!'( 'R )FB31 -  A#

H48:878:<3>)<<3

46 B  (  2  <=3>  B        

    B      ?  (

I 473

47 V-    V  #" !V#"  !U B  S

<=34!'(A- 

  -      !      

<9484>)8>4

48 !!<=38- 

A          5-  H  

7:3=3<=7)3<3=

49 ?- H* ! U ?? <==: (*

  !'()    -        

  %   -  B  ?  )  ?

<9>3847>>>)>87

50 ( %  !?U T BB <=3<

!'()-)

 -:44:79):>8

51 R)T  2      <==7  !'(    .    

-      -      ?

4=8>8;:3=44)3=49

52 !"!<==>!- "*"

*5*!'(%

  -  H      ?    -  $  ?  

3=<3<7737)773:

53 !SUBS<=3=!'(*"

(

54 ,#S **SR'-'Z["SU#

RT<=39 % !'()    -

  -      )  !  

<8<88:)8::

55 B-2''*!  -%U!"!<==3

"*"1

1!'(-H7378:834==)4=<

56 ! ( %FS U ' ' <=33  -

\\1!'()

        * !(    

333

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Long-Read Genome Assemblies Reveal Extraordinary Variation in the Number and Structure of MHC Loci in Birds

Article

Full-text available

Dec 2020

Our knowledge of the Major Histocompatibility Complex (MHC) in birds is limited because it often consists of numerous duplicated genes within individuals that are difficult to assemble with short read sequencing technology. Long-read sequencing provides an opportunity to overcome this limitation because it allows the assembly of long regions with repetitive elements. In this study we used genomes based on long-read sequencing to predict the number and location of MHC loci in a broad range of bird taxa. From the long-read based genomes of 34 species, we found that there was extremely large variation in the number of MHC loci between species. Overall, there were greater numbers of both class I and II loci in passerines than non-passerines. The highest numbers of loci (up to 193 class II loci) were found in manakins (Pipridae), which had previously not been studied at the MHC. Our results provide the first direct evidence from passerine genomes of this high level of duplication. We also found different duplication patterns between species. In some species both MHC class I and II genes were duplicated together, while in most species they were duplicated independently. Our study shows that the analysis of long-read based genomes can dramatically improve in our knowledge of MHC structure, although further improvements in chromosome level assembly are needed to understand the evolutionary mechanisms producing the extraordinary inter-specific variation in the architecture of the MHC region.

The attraction trick: males in early stages of disease become more chemically attractive to Nile tilapia ( Oreochromis niloticus ) females

Article

Aug 2021

In aquatic systems, olfaction plays an important role in acquiring information about the social environment and influences important behaviours in various contexts, including predator avoidance, foraging, aggressive and reproductive behaviour and mate selection. As the presence of diseases might modify individual odour, fish may use the variability in conspecifics odours as an indicator of the health status and infectious load of potential mates. Here, female Nile tilapia were tested for their ability to detect infected males and discriminate between bacterial infected and uninfected individuals by means of chemical cues. Females were allowed to choose between the odours of males infected by A. hydrophila bacteria and uninfected males. Our findings show that female Nile tilapia initially showed a preference for infected males in terms of their first choice in a dichotomous choice test, but the total duration of time spent with the stimulus from infected males was not longer than for the uninfected males. This may indicate that males at early stages of infection, i.e. without advanced clinical signs of infection, emit odours that allow them to enjoy the benefits of socialization when the infection is not yet detected by conspecifics. Thus, in the context of reproduction, males might attract female partners and have some chance of reproducing, before being avoided. This article is protected by copyright. All rights reserved.

Evolution of major histocompatibility complex gene copy number

Article

Full-text available

May 2019
PLOS COMPUT BIOL

MHC genes, which code for proteins responsible for presenting pathogen-derived antigens to the host immune system, show remarkable copy-number variation both between and within species. However, the evolutionary forces driving this variation are poorly understood. Here, we use computer simulations to investigate whether evolution of the number of MHC variants in the genome can be shaped by the number of pathogen species the host population encounters (pathogen richness). Our model assumed that while increasing a range of pathogens recognised, expressing additional MHC variants also incurs costs such as an increased risk of autoimmunity. We found that pathogen richness selected for high MHC copy number only when the costs were low. Furthermore, the shape of the association was modified by the rate of pathogen evolution, with faster pathogen mutation rates selecting for increased host MHC copy number, but only when pathogen richness was low to moderate. Thus, taking into account factors other than pathogen richness may help explain wide variation between vertebrate species in the number of MHC genes. Within population, variation in the number of unique MHC variants carried by individuals (INV) was observed under most parameter combinations, except at low pathogen richness. This variance gave rise to positive correlations between INV and host immunocompetence (proportion of pathogens recognised). However, within-population variation in host immunocompetence declined with pathogen richness. Thus, counterintuitively, pathogens can contribute more to genetic variance for host fitness in species exposed to fewer pathogen species, with consequences to predictions from “Hamilton-Zuk” theory of sexual selection.

Major histocompatibility complex class I diversity limits the repertoire of T cell receptors

Article

Full-text available

Feb 2019
P NATL ACAD SCI USA

Major histocompatibility complex (MHC) genes encode proteins that initiate adaptive immune responses through the presentation of foreign antigens to T cells. The high polymorphism found at these genes, thought to be promoted and maintained by pathogen-mediated selection, contrasts with the limited number of MHC loci found in most vertebrates. Although expressing many diverse MHC genes should broaden the range of detectable pathogens, it has been hypothesized to also cause deletion of larger fractions of self-reactive T cells, leading to a detrimental reduction of the T cell receptor (TCR) repertoire. However, a key prediction of this TCR depletion hypothesis , that the TCR repertoire should be inversely related to the individual MHC diversity, has never been tested. Here, using high-throughput sequencing and advanced sequencing error correction, we provide evidence of such an association in a rodent species with high interindividual variation in the number of expressed MHC molecules, the bank vole (Myodes glareolus). Higher individual diversity of MHC class I, but not class II, was associated with smaller TCR repertoires. Our results thus provide partial support for the TCR depletion model, while also highlighting the complex, potentially MHC class-specific mechanisms by which autoreactivity may trade off against evolutionary expansion of the MHC gene family.

Evolution of Copy Number at the MHC Varies across the Avian Tree of Life

Article

Full-text available

Nov 2018

The evolution of the Major Histocompatibility Complex (MHC) is shaped by frequent gene duplications and deletions, which generate extensive variation in the number of loci (gene copies) between different taxa. Here, we collected estimates of copy number at the MHC for over 250 bird species from 68 families. We found contrasting patterns of copy number evolution between MHC class I and class IIB, which encode receptors for intra- and extra-cellular pathogens, respectively. Across the avian evolutionary tree, there was evidence of accelerated evolution and stabilizing selection acting on copy number at class I, while copy number at class IIB was primarily influenced by fluctuating selection and drift. Reconstruction of MHC copy number variation showed ancestrally low numbers of MHC loci in non-passerines and evolution towards larger numbers of loci in passerines. Different passerine lineages had the highest duplication rates for MHC class I (Sylvioidea) and class IIB (Muscicapoidea and Passeroidea). We also found support for the correlated evolution of MHC copy number and life-history traits such as lifespan and migratory behavior. These results suggest that MHC copy number evolution in birds has been driven by life histories and differences in exposure to intra- and extra-cellular pathogens.

The evolution of immunity in relation to colonization and migration

Article

Full-text available

May 2018
Nat. Ecol. Evol.

Colonization and migration have a crucial effect on patterns of biodiversity, with disease predicted to play an important role in these processes. However, evidence of the effect of pathogens on broad patterns of colonization and migration is limited. Here, using phylogenetic analyses of 1,311 species of Afro-Palaearctic songbirds, we show that colonization events from regions of high (sub-Saharan Africa) to low (the Palaearctic) pathogen diversity were up to 20 times more frequent than the reverse, and that migration has evolved 3 times more frequently from African- as opposed to Palaearctic-resident species. We also found that resident species that colonized the Palaearctic from Africa, as well as African species that evolved long-distance migration to breed in the Palaearctic, have reduced diversity of key immune genes associated with pathogen recognition (major histocompatibility complex class I). These results suggest that changes in the pathogen community that occur during colonization and migration shape the evolution of the immune system, potentially by adjusting the trade-off between the benefits of extensive pathogen recognition and the costs of immunopathology that result from high major histocompatibility complex class I diversity.

Patterns of MHC-dependent mate selection in humans and nonhuman primates: A meta-analysis

Article

Full-text available

Nov 2016
MOL ECOL

Genes of the major histocompatibility complex (MHC) in vertebrates are integral for effective adaptive immune response and are associated with sexual selection. Evidence from a range of vertebrates supports MHC-based preference for diverse and dissimilar mating partners, but evidence from human mate choice studies has been disparate and controversial. Methodologies and sampling peculiarities specific to human studies make it difficult to know whether wide discrepancies in results among human populations are real or artifact. To better understand what processes may affect MHC-mediated mate choice across humans and non-human primates we performed phylogenetically controlled meta-analyses using 58 effect sizes from 30 studies across 7 primate species. Primates showed a general trend favoring more MHC-diverse mates, which was statistically significant for humans. In contrast, there was no tendency for MHC-dissimilar mate choice, and for humans, we observed effect sizes indicating selection of both MHC-dissimilar and MHC-similar mates. Focusing on MHC-similar effect sizes only, we found evidence that preference for MHC-similarity was an artifact of population ethnic heterogeneity in observational studies but not among experimental studies with more control over socio-cultural biases. This suggests that human assortative mating biases may be responsible for some patterns of MHC-based mate choice. Additionally, the overall effect sizes of primate MHC-based mating preferences are relatively weak (Fisher's Z correlation coefficient for dissimilarity Zr = 0.044, diversity Zr = 0.153), calling for careful sampling design in future studies. Overall, our results indicate that preference for more MHC diverse mates is significant for humans and likely conserved across primates. This article is protected by copyright. All rights reserved.

Evolution of the immune system influences speciation rates in teleost fishes

Article

Full-text available

Aug 2016
Nat Genet

Teleost fishes constitute the most species-rich vertebrate clade and exhibit extensive genetic and phenotypic variation, including diverse immune defense strategies. The genomic basis of a particularly aberrant strategy is exemplified by Atlantic cod, in which a loss of major histocompatibility complex (MHC) II functionality coincides with a marked expansion of MHC I genes. Through low-coverage genome sequencing (9-39×), assembly and comparative analyses for 66 teleost species, we show here that MHC II is missing in the entire Gadiformes lineage and thus was lost once in their common ancestor. In contrast, we find that MHC I gene expansions have occurred multiple times, both inside and outside this clade. Moreover, we identify an association between high MHC I copy number and elevated speciation rates using trait-dependent diversification models. Our results extend current understanding of the plasticity of the adaptive immune system and suggest an important role for immune-related genes in animal diversification.

Blood parasites shape extreme MHC diversity in a migratory passerine

Article

Apr 2018
MOL ECOL

Pathogens are one of the main forces driving the evolution and maintenance of the highly polymorphic genes of the vertebrate major histocompatibility complex (MHC). Although MHC proteins are crucial in pathogen recognition, it is still poorly understood how pathogen‐mediated selection promotes and maintains MHC diversity, and especially so in host species with highly duplicated MHC genes. Sedge warblers (Acrocephalus schoenobaenus) have highly duplicated MHC genes and using data from high‐throughput MHC genotyping we were able to investigate to what extent avian malaria parasites explain temporal MHC class I supertype fluctuations in a long‐term study population. We investigated infection status and infection intensities of two different strains of Haemoproteus, i.e. avian malaria parasites that are known to have significant fitness consequences in sedge warblers. We found that prevalence of avian malaria in carriers of specific MHC class I supertypes was a significant predictor of their frequency changes between years. This finding suggests that avian malaria infections partly drive the temporal fluctuations of the MHC class I supertypes. Furthermore, we found that individuals with a large number of different supertypes had higher resistance to avian malaria, but there was no evidence for an optimal MHC class I diversity. Thus, the two studied malaria parasite strains appear to select for a high MHC class I supertype diversity. Such selection may explain the maintenance of the extremely high number of MHC class I gene copies in sedge warblers, and possibly also in other passerines where avian malaria is a common disease.

Immunogenetic novelty confers a selective advantage in host–pathogen coevolution

Article

Jan 2018

The major histocompatibility complex (MHC) is crucial to the adaptive immune response of vertebrates and is among the most polymorphic gene families known. Its high diversity is usually attributed to selection imposed by fast-evolving pathogens. Pathogens are thought to evolve to escape recognition by common immune alleles, and, hence, novel MHC alleles, introduced through mutation, recombination, or gene flow, are predicted to give hosts superior resistance. Although this theoretical prediction underpins host-pathogen "Red Queen" coevolution, it has not been demonstrated in the context of natural MHC diversity. Here, we experimentally tested whether novel MHC variants (both alleles and functional "supertypes") increased resistance of guppies (Poecilia reticulata) to a common ectoparasite (Gyrodactylus turnbulli). We used exposure-controlled infection trials with wild-sourced parasites, and Gyrodactylus-naïve host fish that were F2 descendants of crossed wild populations. Hosts carrying MHC variants (alleles or supertypes) that were new to a given parasite population experienced a 35-37% reduction in infection intensity, but the number of MHC variants carried by an individual, analogous to heterozygosity in single-locus systems, was not a significant predictor. Our results provide direct evidence of novel MHC variant advantage, confirming a fundamental mechanism underpinning the exceptional polymorphism of this gene family and highlighting the role of immunogenetic novelty in host-pathogen coevolution.

R: A Language and Environment for Statistical Computing

Book

Jan 2015

Core R Team

De novo transcriptome assembly facilitates characterisation of fast-evolving gene families, MHC class I in the bank vole (Myodes glareolus)

Article

Apr 2017

The major histocompatibility complex (MHC) plays a central role in the adaptive immune response and is the most polymorphic gene family in vertebrates. Although high-throughput sequencing has increasingly been used for genotyping families of co-amplifying MHC genes, its potential to facilitate early steps in the characterisation of MHC variation in nonmodel organism has not been fully explored. In this study we evaluated the usefulness of de novo transcriptome assembly in characterisation of MHC sequence diversity. We found that although de novo transcriptome assembly of MHC I genes does not reconstruct sequences of individual alleles, it does allow the identification of conserved regions for PCR primer design. Using the newly designed primers, we characterised MHC I sequences in the bank vole. Phylogenetic analysis of the partial MHC I coding sequence (2-4 exons) of the bank vole revealed a lack of orthology to MHC I of other Cricetidae, consistent with the high gene turnover of this region. The diversity of expressed alleles was characterised using ultra-deep sequencing of the third exon that codes for the peptide-binding region of the MHC molecule. High allelic diversity was demonstrated, with 72 alleles found in 29 individuals. Interindividual variation in the number of expressed loci was found, with the number of alleles per individual ranging from 5 to 14. Strong signatures of positive selection were found for 8 amino acid sites, most of which are inferred to bind antigens in human MHC, indicating conservation of structure despite rapid sequence evolution.Heredity advance online publication, 26 October 2016; doi:10.1038/hdy.2016.105.