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With muta­tions, it turns out that con­text can be every­thing in deter­min­ing whether or not they are ben­e­fi­cial to their evo­lu­tion­ary fate.

Accord­ing to the tra­di­tional view among biol­o­gists, a cen­tral tenet of evo­lu­tion­ary biol­ogy has been that the evo­lu­tion­ary fates of new muta­tions depend on whether their effects are good, bad or incon­se­quen­tial with respect to repro­duc­tive suc­cess. Cen­tral to this view is that “good” muta­tions are always good and lead to repro­duc­tive suc­cess, while “bad” muta­tions are always bad and will be quickly weeded out of the gene pool. How­ever, new research led by evo­lu­tion­ary biol­o­gist Jay Storz of the Uni­ver­sity of Nebraska-​Lincoln (UNL) has found that whether a given muta­tion is good or bad is often deter­mined by other muta­tions asso­ci­ated with it. In other words, genetic evo­lu­tion is context-​dependent.

In a study to be pub­lished in the June 14 issue of Sci­ence, Storz and col­leagues Natara­jan and Inoguchi at UNL, and Weber and Fago at Aarhus Uni­ver­sity in Den­mark report that an indi­vid­ual muta­tion can be ben­e­fi­cial if it occurs in com­bi­na­tion with cer­tain other muta­tions, but the same muta­tion can detri­men­tal to the organ­ism if it occurs in other combinations.

The researchers stud­ied muta­tions that alter the func­tion of haemo­glo­bin, the pro­tein in charge of trans­port­ing oxy­gen in the blood. Phys­i­ol­o­gists have long known that many high-​altitude ani­mals have evolved hemo­glo­bins with high affini­ties for oxy­gen, which can enhance oxy­gen uptake in thin air. Ear­lier research by Storz’s group on pop­u­la­tions of North Amer­i­can deer mice that are native to high and low alti­tudes had found that the high-​altitude mice had evolved hemo­glo­bins with an increased oxygen-​binding affin­ity — and that this dif­fer­ence is attrib­ut­able to the com­bined effects of genetic muta­tions at 12 dif­fer­ent sites in the haemo­glo­bin protein.

For the dis­cov­ery reported in Sci­ence, the researchers used a tech­nique called “pro­tein engi­neer­ing” to syn­the­size haemo­glo­bin pro­teins that con­tained each of the nat­u­rally occur­ring muta­tions in all pos­si­ble multi-​site combinations.

“One of the impor­tant impli­ca­tions is that if there are inter­ac­tions between muta­tions, then some muta­tional path­ways of evo­lu­tion may be more acces­si­ble than oth­ers. The evo­lu­tion­ary fate of a new muta­tion will depend crit­i­cally on which other muta­tions have already occurred. The order in which muta­tions occur can deter­mine whether evo­lu­tion is more likely to fol­low some path­ways rather than oth­ers. Evo­lu­tion may fol­low cer­tain path­ways just because cer­tain inter­ac­tions may be neg­a­tive, other inter­ac­tions may be pos­i­tive. These kinds of inter­ac­tion effects deter­mine what muta­tional path­ways are open and avail­able for evo­lu­tion,” accord­ing to Storz.

(Source: UNL news release, 13.06.2013)