A Tale of Three Yeasts

by Merry Youle

This is a story of three species of yeast, three closely re­lated Sac­cha­romyces. For each of them, the en­tire genome se­quence is known. So closely re­lated are they that more than 99.95% of their ge­nes are con­served. In other taxa, they would be con­sid­ered the same species. Nonethe­less, they all oc­cupy slightly dif­fer­ent eco­log­i­cal niches. S. cere­visiae, man's part­ner in brew­ing for more than 5 mil­len­nia, is typ­i­cally found on fruit such as grapes and figs. S. bayanus, a cryophilic species which can grow at tem­per­a­tures as low as 4° C., has played a role in cider and wine fer­men­ta­tion. S. mikatae, a rel­a­tive new­comer, is found in nu­tri­ent-poor habi­tats such as soil and de­cay­ing leaves.

Yeast colonies on grapes; large enough to see the yeast colonies. Source

Diploid cells of all three switch from a bud­ding yeast to a pseudo­hy­phal form of growth in re­sponse to nu­tri­ent li­mitation, pre­sum­ably to en­able them to bet­ter search for food. In the lab, one can in­duce this shift by starv­ing them for ni­tro­gen. This abil­ity to switch growth forms, called di­mor­phism, is shared by some im­por­tant patho­gens such as the hu­man pathogen, Can­dida al­bi­cans, and the corn smut agent, Usti­lago may­dis. It has been known for some time that two well-stud­ied tran­scrip­tion fac­tors (TFs), Ste12 and Tec1, act in con­cert to or­ches­trate the switch to pseudo­hy­phal growth. Thus it is not sur­pris­ing that their genes are among the ones con­served in these three species.

The au­thors of a re­cent re­search pa­per saw this as an op­por­tu­nity to in­ves­ti­gate an in­trigu­ing evo­lu­tion­ary ques­tion. Evo­lu­tion­ary di­ver­gence can re­sult ei­ther from changes in gene composi­tion or in gene reg­u­la­tion. These three yeasts, with all but 0.05% of their genes in com­mon and their con­served TFs, pro­vide the op­por­tu­nity to ask if the reg­u­la­tory tar­gets for these TFs have di­verged, since the TF pro­teins them­selves have not.

TFs bind to spe­cific re­gions of the DNA (pro­moter re­gions) and reg­u­late the tran­scrip­tion of genes down­stream from each bind­ing site. Can one de­ter­mine whether a par­tic­u­lar TF is reg­u­lat­ing the same genes in all three species? These re­searchers had pre­vi­ously re­ported an im­proved tech­nique that en­ables them to do just that. Their method com­bines im­muno­pre­cip­i­ta­tion (to as­say the for­ma­tion in vivo of spe­cific TF-DNA com­plexes) with high res­o­lu­tion DNA mi­croar­rays (to map the lo­ca­tion of those TF bind­ing sites). The next step? Map the DNA sites where Tec1 and Ste12 bind dur­ing the in­duced switch to pseudo­hy­phal growth in each of these three species.

Only 21% of the Ste12 bind­ing sites and 20% of the Tec1 bind­ing sites were con­served across all three species. Thus 79% and 80%, re­spec­tively, of the bind­ing sites had changed in at least one species. The au­thors note the evo­lu­tion­ary im­pli­ca­tions:

Tran­scrip­tion fac­tor bind­ing sites have there­fore di­verged sub­stan­tially faster than or­tholog con­tent. Thus, gene reg­u­la­tion re­sult­ing from tran­scrip­tion fac­tor bind­ing is likely to be a ma­jor cause of di­ver­gence be­tween re­lated species.

What does this show? Cru­cial evo­lu­tion­ary changes don't nec­es­sar­ily re­quire large ge­nomic alter­ations. Granted, this is not ex­actly news. Still we find this to be a par­tic­u­larly el­e­gant ex­am­ple il­lus­trat­ing the evo­lu­tion­ary sen­si­tiv­ity of reg­u­la­tory se­quences – some­thing fun­da­men­tal that would have es­caped ge­nomic analy­sis. Evo­lu­tion­ary lever­age.

We thank Bob Mur­ray for call­ing our at­ten­tion to this ar­ti­cle. He con­cluded his mes­sage with: "Who reg­u­lates the reg­u­la­tors?"