Does genetic diversity protect host populations from parasites?

Yes, accord­ing to a new study in Evol­u­tion Let­ters, though the res­ults of its meta-ana­lyses find sub­stan­tial vari­ation in the degree to which genet­ic diversity reduces para­sit­ism in host pop­u­la­tions. Dr. Aman­da Kyle Gib­son explains.

Wheth­er we be clini­cians, agri­cul­tur­al sci­ent­ists, epi­demi­olo­gists, or evol­u­tion­ary bio­lo­gists, a shared ques­tion among research­ers of infec­tious dis­eases is: why is an infec­tious dis­ease so pre­val­ent or so severe in this pop­u­la­tion of hosts and not this oth­er one?  And what can we do about it?  One of the most gen­er­al and long-stand­ing hypo­theses to address this ques­tion pro­poses that host pop­u­la­tions with reduced genet­ic diversity exper­i­ence increased bur­dens of para­sites rel­at­ive to genet­ic­ally diverse hosts populations. 

You might be famil­i­ar with this idea from the notori­ous epi­dem­ics that have decim­ated crops planted in mono­cul­tures, where one or many fields are planted with a single cul­tivar, or gen­o­type, of the crop plant.  These epi­dem­ics include the out­break of cof­fee rust that decim­ated Sri Lanka’s cof­fee industry in the mid-1800’s, the rap­id spread of Phytoph­thora infest­ans that led to the Irish Potato Fam­ine in the 1840’s, and the recur­ring threat of fusari­um wilt to glob­al banana cul­tiv­a­tion.  The com­mon explan­a­tion for these cata­strophes is the genet­ic homo­gen­eity of crop fields: once para­sites can infect one host in a mono­cul­ture, they can read­ily leap to indi­vidu­als closely related to that host, ulti­mately infect­ing the entire field, maybe even all the fields in a region.  This argu­ment pro­poses a solu­tion: if para­sites trans­mit less read­ily to hosts that are genet­ic­ally dis­tinct from the ori­gin­al host, then the spread of dis­ease may be slowed in poly­cul­tures, where fields are planted with mul­tiple gen­o­types of the crop plant. 

These ideas don’t just mat­ter for agri­cul­ture.  Endangered spe­cies lose genet­ic diversity as their pop­u­la­tions become small and frag­men­ted.  This loss of genet­ic diversity is a prom­in­ent hypo­thes­is for the epi­dem­ics threat­en­ing endangered spe­cies like the Tas­mani­an Dev­il and the black-footed fer­ret.  The hypo­thes­ized pro­tect­ive effect of genet­ic diversity has even helped us under­stand fun­da­ment­al puzzles in evol­u­tion­ary bio­logy – the pre­val­ence of costly strategies, like sexu­al repro­duc­tion and mat­ing with mul­tiple males, that can main­tain or increase genet­ic diversity in lineages. 

To say that I’ve relied on these ideas in my research career would be an under­state­ment.  Genet­ic diversity’s gen­er­al role as a lim­it on dis­ease spread is fun­da­ment­al to major evol­u­tion­ary ideas, like the Red Queen hypo­thes­is.  So whenev­er I’ve ref­er­enced the idea – cit­ing thought­ful per­spect­ives (Haldane 1949; King and Lively 2012; Mun­dt 2002; Sher­man et al. 1988) and com­pel­ling exper­i­ment­al tests (Ebert et al. 2007; Mea­gh­er 1999; Schmid 1994; Zhu et al. 2000) – I’ve always asked myself, how gen­er­al is the pro­tect­ive effect of genet­ic diversity really? How strong is it on aver­age? Does the effect vary? How much? Under what con­di­tions?  The answers to these ques­tions mat­ter – they help evol­u­tion­ary bio­lo­gists like me decide how much con­fid­ence to have in the assump­tions we make and give prac­ti­tion­ers in applied fields data to determ­ine if the poten­tial bene­fits of genet­ic diver­si­fic­a­tion are suf­fi­ciently prom­ising to jus­ti­fy the invest­ment.  We can arrive at answers to these ques­tions via an approach known as meta-ana­lys­is, the syn­thes­is of res­ults from mul­tiple stud­ies to quanti­fy the mean and vari­ance of a variable’s effect.

My coau­thor Anna Nguy­en and I set off to find the right lit­er­at­ure for this meta-ana­lys­is.  In comb­ing through the lit­er­at­ure, we were imme­di­ately struck by the incred­ible vari­ety of stud­ies address­ing the rela­tion­ship between genet­ic diversity and dis­ease.  We slowly developed our lit­er­at­ure search pro­tocol, nar­row­ing our focus to stud­ies that quan­ti­fied some meas­ure of para­sit­ism (e.g. pre­val­ence) in host pop­u­la­tions, arti­fi­cial or nat­ur­al, that var­ied in their genet­ic diversity.  We focused on genet­ic vari­ation between indi­vidu­als with­in a pop­u­la­tion, rather than the gen­om­ic het­ero­zy­gos­ity of indi­vidu­als them­selves.  That factor is for anoth­er team to tackle!  We ended up with 102 eli­gible stud­ies, rep­res­ent­ing invest­ig­a­tions of both exper­i­ment­al and nat­ur­al pop­u­la­tions of plant (some crops), ver­teb­rate, inver­teb­rate, and bac­teri­al hosts para­sit­ized by vir­al, pro­to­zoal, fungal, bac­teri­al and anim­al parasites. 

We first focused on exper­i­ment­al stud­ies.  In these, research­ers would assemble arti­fi­cial host pop­u­la­tions with high diversity by, for example, com­bin­ing mul­tiple host gen­o­types or col­lect­ing off­spring from a female mated with mul­tiple males.  Host pop­u­la­tions with low diversity instead would have indi­vidu­als of a single gen­o­type or off­spring from a female mated with a single male.  Research­ers would then expose these pop­u­la­tions to para­sites, arti­fi­cially in the lab or nat­ur­ally in the field.  If genet­ic diversity does pro­tect against para­sit­ism, you’d pre­dict less para­sit­ism on aver­age in the high diversity host pop­u­la­tions than the low diversity ones.  Our syn­thes­is found strong sup­port for this pre­dic­tion in the lit­er­at­ure.  Increas­ing genet­ic diversity reduced para­sit­ism by ~20% on aver­age across 25 stud­ies of non-crop hosts. This estim­ate resembles that from Ekroth et al. (2019), a meta-ana­lys­is of a sim­il­ar set of stud­ies.  A reduc­tion in para­sit­ism of 20% is note­worthy, but it pales in com­par­is­on to the effect of genet­ic diversity in crop exper­i­ments: across 55 stud­ies, poly­cul­tures had ~50% less para­sit­ism on aver­age than monocultures. 

Giv­en this effect in exper­i­ment­al pop­u­la­tions, we moved on to test­ing the same idea in obser­va­tion­al stud­ies of nat­ur­al pop­u­la­tions.  We defined obser­va­tion­al stud­ies as those in which the research­ers played no role in manip­u­lat­ing the genet­ic diversity or para­site expos­ure of the host pop­u­la­tions.  For example, Mea­gh­er (1999) meas­ured the pre­val­ence of nem­at­odes in nine wild pop­u­la­tions of deer mice in North­ern Michigan, USA.  If genet­ic diversity pro­tects against para­sit­ism, it seems intu­it­ive to pre­dict a neg­at­ive cor­rel­a­tion between pop­u­la­tion-level estim­ates of diversity and para­sit­ism.  Our syn­thes­is of 22 obser­va­tion­al stud­ies did not sup­port this pre­dic­tion.  There are some inter­est­ing reas­ons that we actu­ally expec­ted this res­ult, and I’ll leave those details for the paper.  The key points are these: first, a pro­tect­ive effect of genet­ic diversity may res­ult in strongly pos­it­ive or neg­at­ive cor­rel­a­tions between pop­u­la­tion-level estim­ates of diversity and para­sit­ism, depend­ing on the set of pop­u­la­tions you’re look­ing at.  Second, we did find a neg­at­ive cor­rel­a­tion between diversity and para­sit­ism in pop­u­la­tions of threatened host spe­cies.  We’d like to get our hands on more data with which to bet­ter test this rela­tion­ship, but it sup­ports the idea that con­ser­va­tion of genet­ic diversity is an import­ant con­sid­er­a­tion in man­age­ment of threatened species.

  

A sum­mary of our res­ults.  Hedges’ g is the mean dif­fer­ence in para­sit­ism between high and low diversity host pop­u­la­tions, stand­ard­ized by the vari­ation between rep­lic­ate pop­u­la­tions.  Neg­at­ive val­ues mean that genet­ic­ally diverse pop­u­la­tions have less dis­ease on aver­age.  The mag­nitude of Hedges’ g gives us a sense of the mag­nitude of the effect.  The mag­nitude of the mean effect for exper­i­ment­al crop stud­ies is con­sist­ent with a strong effect of genet­ic diversity on para­sit­ism, while the mag­nitude of the mean effect for exper­i­ment­al non-crop stud­ies is mod­er­ate.  We see no mean effect in obser­va­tion­al studies. 

The res­ults of this study give sub­stan­tial weight to the long-stand­ing hypo­thes­is that genet­ic diversity of host pop­u­la­tions can lim­it para­sit­ism.  Our syn­thes­is of agri­cul­tur­al exper­i­ments under­scores poly­cul­ture as a sus­tain­able meas­ure for con­trolling dis­ease and main­tain­ing yield in crop fields.  Our syn­thes­is of exper­i­ments in non-agri­cul­tur­al sys­tems sup­ports hypo­theses that pro­pose para­sites as an explan­a­tion for the puzz­ling pre­val­ence of strategies like sex and poly­andry.  Our ana­lyses also warn of the danger posed by dis­ease out­breaks when human actions rob nat­ur­al pop­u­la­tions of their genet­ic diversity.  We hope our find­ings spur the use of genet­ic diver­si­fic­a­tion as a tool in dis­ease man­age­ment and motiv­ate research into the curi­ous gaps in the lit­er­at­ure revealed by this synthesis. 

Dr. Aman­da Kyle Gib­son is an assist­ant pro­fess­or at the Uni­ver­sity of Vir­gin­ia.  She co-authored the ori­gin­al art­icle with Anna Nguy­en, a third-year under­gradu­ate research­er.  It is freely avail­able to read and down­load from Evol­u­tion Letters.

Ref­er­ences

Ebert, D., F. Alter­matt, and S. Lass. 2007. A short term bene­fit for out­cross­ing in a Daph­nia meta­pop­u­la­tion in rela­tion to para­sit­ism. Journ­al of the Roy­al Soci­ety Inter­face 4:777–785.

Ekroth, A. K., C. Rafaluk-Mohr, and K. C. King. 2019. Host genet­ic diversity lim­its para­site suc­cess bey­ond agri­cul­tur­al sys­tems: a meta-ana­lys­is. Pro­ceed­ings of the Roy­al Soci­ety B 286:20191811.

Haldane, J. B. S. 1949. Dis­ease and evol­u­tion. La Ricerca Sci­en­ti­fica 19 68–76.

King, K. C., and C. M. Lively. 2012. Does genet­ic diversity lim­it dis­ease spread in nat­ur­al host pop­u­la­tions? Hered­ity 109:199–203.

Mea­gh­er, S. 1999. Genet­ic diversity and Capil­laria hep­at­ica (Nem­at­oda) pre­val­ence in Michigan deer mouse pop­u­la­tions. Evol­u­tion 53:1318–1324.

Mun­dt, C. C. 2002. Use of mul­til­ine cul­tivars and cul­tivar mix­tures for dis­ease man­age­ment. Annu­al Review of Phyto­path­o­logy 40:381–410.

Schmid, B. 1994. Effects of genet­ic diversity in exper­i­ment­al stands of Sol­id­ago altis­sima–evid­ence for the poten­tial role of patho­gens as select­ive agents in plant pop­u­la­tions. Journ­al of Eco­logy 82:165–175.

Sher­man, P. W., T. D. See­ley, and H. K. Reeve. 1988. Para­sites, patho­gens, and poly­andry in social Hymen­op­tera. Amer­ic­an Nat­ur­al­ist 131:602–610.

Zhu, Y., H. Chen, J. Fan, Y. Wang, Y. Li, J. Chen, J. Fan et al. 2000. Genet­ic diversity and dis­ease con­trol in rice. Nature 406:718.