Testosterone relaxes genetic constraints between the sexes

A new study pub­lished in Evol­u­tion Let­ters has shown that testoster­one shapes the under­ly­ing genet­ic para­met­ers determ­in­ing how pop­u­la­tions respond to selec­tion. Authors Tyler Wittman and Robert Cox tell us more.

In many spe­cies, females and males look strik­ingly dif­fer­ent. This phe­nomen­on of sexu­al dimorph­ism is quite com­mon, but it is puzz­ling when you con­sider that both sexes share most of the same genes. For example, male brown anole liz­ards weigh twice as much as females and have a large and brightly colored throat fan (dew­lap) that is ten times smal­ler in females. Yet, the vast major­ity of an anole’s genes are present in both sexes. This means that nat­ur­al or sexu­al selec­tion for lar­ger size or bright­er col­or­a­tion in males should lead to the inher­it­ance of these same traits by females. How do females and males evolve to be so dif­fer­ent des­pite shar­ing most of the same genes? 

We can estim­ate the extent to which shared genes are likely to con­strain evol­u­tion by meas­ur­ing the degree to which traits are genet­ic­ally cor­rel­ated between females and males. For example, the hue of the anole dew­lap is strongly genet­ic­ally cor­rel­ated between the sexes. This means that males with red­der dew­laps will have sis­ters, moth­ers, and daugh­ters with red­der dew­laps, where­as males with yel­low­er dew­laps will have female rel­at­ives with yel­low­er dew­laps. How­ever, genet­ic cor­rel­a­tions for highly sexu­ally dimorph­ic traits, such as the size or bright­ness of the dew­lap, are much weak­er between females and males. How are these genet­ic cor­rel­a­tions weakened to facil­it­ate the evol­u­tion of sexu­al dimorphism?

One pos­sib­il­ity is that sex hor­mones such as testoster­one, which cir­cu­lates at high­er levels in males than in females, enables the sexes to express their shared genes in dif­fer­ent ways. Although we did not meas­ure gene expres­sion in this study, it is well known that testoster­one and its recept­or can inter­act with DNA to increase or decrease the expres­sion of hun­dreds of genes at a time. There­fore, we decided to ask wheth­er a single hor­mone could be respons­ible for sim­ul­tan­eously redu­cing genet­ic cor­rel­a­tions for a vari­ety of sexu­ally dimorph­ic traits. 

Test­ing this idea required breed­ing hun­dreds of liz­ards for more than a year to pro­duce over a thou­sand off­spring (which would not have been pos­sible without the help of many ded­ic­ated UVA stu­dents!). Next, we split each anole fam­ily so that half of the sib­lings received a slow-release testoster­one implant at three months of age, while their broth­ers and sis­ters received an empty implant as a con­trol. In juven­ile males, testoster­one levels are just begin­ning to increase at this age (sim­il­ar to puberty in mam­mals). What would an increase in testoster­one do to juven­ile females, who nat­ur­ally have low testoster­one levels through­out their lives? 

From the image above, you can see the dra­mat­ic effects of testoster­one on the size and col­or of the dew­lap in females. Testoster­one also sig­ni­fic­antly enhanced the growth of females. In oth­er words, testoster­one made females more sim­il­ar to males in terms of body and dew­lap size, and it elim­in­ated most sex dif­fer­ences in dew­lap col­or. These res­ults are rather strik­ing, but not exactly news­worthy – it is already well known that testoster­one reg­u­lates sex dif­fer­ences in growth and col­or­a­tion in a vari­ety of mam­mals, birds, rep­tiles, amphi­bi­ans, and fish.

Because we knew the genet­ic rela­tion­ships of all the anoles in our study, we were able to go a step fur­ther to provide the first dir­ect evid­ence that testoster­one weak­ens genet­ic cor­rel­a­tions between females and males. As seen in the fig­ure below, genet­ic cor­rel­a­tions between con­trol females and con­trol males are weak for most traits except dew­lap hue, sug­gest­ing that nat­ur­al sex dif­fer­ences in testoster­one allow the sexes to express their shared genes in dif­fer­ent ways. How­ever, genet­ic cor­rel­a­tions are sig­ni­fic­antly high­er between females treated with testoster­one and these same con­trol males, as expec­ted if the sexes share the same genes and the res­ult­ing genet­ic cor­rel­a­tions are only weakened when they dif­fer in testoster­one levels. 

Going a step fur­ther, we sim­u­lated sex dif­fer­ences in nat­ur­al selec­tion to show that the weak genet­ic cor­rel­a­tions between con­trol females and con­trol males are much less likely to con­strain their evol­u­tion than the strong cor­rel­a­tions that arise when both sexes have high testoster­one levels. We also found that con­trol females dif­fer from con­trol males in the way that pairs of traits are genet­ic­ally cor­rel­ated with each oth­er. How­ever, when females receive testoster­one, their traits become genet­ic­ally cor­rel­ated in a way that resembles males. 

Our study is the first to dir­ectly show that hor­mon­al pleio­tropy – when one hor­mone influ­ences mul­tiple traits – struc­tures pat­terns of genet­ic cor­rel­a­tion between the sexes and between dif­fer­ent traits. Because these pat­terns of genet­ic cor­rel­a­tion should influ­ence how females and males evolve in response to nat­ur­al and sexu­al selec­tion, our study sug­gests that hor­mones like testoster­one play import­ant roles in evol­u­tion, help­ing the sexes evolve dra­mat­ic dif­fer­ences des­pite shar­ing a genome.

Tyler Wittman is a PhD can­did­ate in the lab of Dr Robert Cox at the Depart­ment of Bio­logy, Uni­ver­sity of Vir­gin­ia. The ori­gin­al art­icle is freely avail­able to read and down­load from Evol­u­tion Letters.