Media Releases

Why we’re smarter than chickens

August 20, 2015

Researchers at U of T’s Donnelly Centre uncover protein part that controls neuron development

TORONTO, ON – Toron­to researchers have dis­cov­ered that a sin­gle mol­e­c­u­lar event in our cells could hold the key to how we evolved to become the smartest ani­mal on the plan­et.

Ben­jamin Blencowe, a pro­fes­sor in the Uni­ver­si­ty of Toronto’s Don­nel­ly Cen­tre and Ban­bury Chair in Med­ical Research, and his team have uncov­ered how a small change in a pro­tein called PTBP1 can spur the cre­ation of neu­rons – cells that make the brain – that could have fuelled the evo­lu­tion of mam­malian brains to become the largest and most com­plex among ver­te­brates.
The study is pub­lished in the August 20 issue of Sci­ence (

Brain size and com­plex­i­ty vary enor­mous­ly across ver­te­brates, but it is not clear how these dif­fer­ences came about. Humans and frogs, for exam­ple, have been evolv­ing sep­a­rate­ly for 350 mil­lion years and have very dif­fer­ent brain abil­i­ties. Yet sci­en­tists have shown that they use a remark­ably sim­i­lar reper­toire of genes to build organs in the body.

So how is it that a sim­i­lar num­ber of genes, that are also switched on or off in sim­i­lar ways in diverse ver­te­brate species, gen­er­ate a vast range of organ size and com­plex­i­ty?

The key lays in the process that Blencowe’s group stud­ies, known as alter­na­tive splic­ing (AS), where­by gene prod­ucts are assem­bled into pro­teins, which are the build­ing blocks of life. Dur­ing AS, gene frag­ments – called exons – are shuf­fled to make dif­fer­ent pro­tein shapes. It’s like LEGO, where some frag­ments can be miss­ing from the final pro­tein shape.

AS enables cells to make more than one pro­tein from a sin­gle gene, so that the total num­ber of dif­fer­ent pro­teins in a cell great­ly sur­pass­es the num­ber of avail­able genes. A cell’s abil­i­ty to reg­u­late pro­tein diver­si­ty at any giv­en time reflects its abil­i­ty to take on dif­fer­ent roles in the body. Blencowe’s pre­vi­ous work showed that AS preva­lence increas­es with ver­te­brate com­plex­i­ty. So although the genes that make bod­ies of ver­te­brates might be sim­i­lar, the pro­teins they give rise to are far more diverse in ani­mals such as mam­mals, than in birds and frogs.

And nowhere is AS more wide­spread than in the brain.

“We want­ed to see if AS could dri­ve mor­pho­log­i­cal dif­fer­ences in the brains of dif­fer­ent ver­te­brate species,” says Serge Guer­oussov, a grad­u­ate stu­dent in Blencowe’s lab who is the lead author of the study. Guer­oussov pre­vi­ous­ly helped iden­ti­fy PTBP1 as a pro­tein that takes on anoth­er form in mam­mals, in addi­tion to the one com­mon to all ver­te­brates. The sec­ond form of mam­malian PTBP1 is short­er because a small frag­ment is omit­ted dur­ing AS and does not make it into the final pro­tein shape.

Could this new­ly acquired, mam­malian ver­sion of PTBP1 give clues to how our brains evolved?

PTBP1 is both a tar­get and major reg­u­la­tor of AS. PTBP1’s job in a cell is to stop it from becom­ing a neu­ron by hold­ing off AS of hun­dreds of oth­er gene prod­ucts.

Guer­oussov showed that in mam­malian cells, the pres­ence of the sec­ond, short­er ver­sion of PTBP1 unleash­es a cas­cade of AS events, tip­ping the scales of pro­tein bal­ance so that a cell becomes a neu­ron.

What’s more, when Guer­oussov engi­neered chick­en cells to make the short­er, mam­malian-like, PTBP1, this trig­gered AS events that are found in mam­mals.

“One inter­est­ing impli­ca­tion of our work is that this par­tic­u­lar switch between the two ver­sions of PTBP1 could have affect­ed the tim­ing of when neu­rons are made in the embryo in a way that cre­ates dif­fer­ences in mor­pho­log­i­cal com­plex­i­ty and brain size,” says Blencowe, who is also a pro­fes­sor in the Depart­ment of Mol­e­c­u­lar Genet­ics.

As sci­en­tists con­tin­ue to sift through count­less mol­e­c­u­lar events occur­ring in our cells, they’ll keep find­ing clues as to how our bod­ies and minds came to be.

“This is the tip of an ice­berg in terms of the full reper­toire of AS changes that like­ly have con­tributed major roles in dri­ving evo­lu­tion­ary dif­fer­ences,” says Blencowe.


For more infor­ma­tion:

Jovana Drin­jakovic, PhD
Don­nel­ly Cen­tre, Uni­ver­si­ty of Toron­to
Tel: +1.416.946.8253
Cell: +1.416.543.7820