Another Reason Why You are Not a Chimp

U. Toronto

Humans and chimpanzees share remarkably similar sets of genes.  When measured conventionally, the genes of humans and the genes of chimps are 99% alike.   And yet, chimps do not build cities, do not publish encyclopedias, and do not launch spaceships to Mars and beyond.


Two recent studies:

N. L. Barbosa-Morais et al., “The Evolutionary Landscape of alternative splicing in vertebrate species,” Science, 388, 1587-93, 2012.

J. Merkin et al., “Evolutionary dynamics of gene and isoform regulation in mammalian tissues,”Science, 388, 1593-99, 2012.

provide new information on how two species with very similar DNA patterns can develop so differently in the real world.

The studies from MIT and the University of Toronto, reveal the remarkable degree of difference alternative gene splicing between species -- resulting in distinctly different proteins from the same gene.

“It was somewhat generally assumed that splicing differences that you see between brain and muscle in the mouse would be similar between brain and muscle in the human,” said Donny Licatalosi, professor of RNA molecular biology at Case Western Reserve University in Cleveland, Ohio, who did not participate in the studies, “but what both of these studies are showing is that is not the case. There is a large amount of species-specific alternative splicing.”

...“how do physical and behavioral differences arise if we have a very similar set of genes to that of the mouse, chicken, or frog?” said Ben Blencowe, a cell and molecular biology professor at the University of Toronto, who led one of the studies. A commonly discussed mechanism was variable levels of gene expression, but both Blencowe and Chris Burge, biology and biological engineering professor at Massachusetts Institute of Technology and lead author of the second paper, found that gene expression is relatively conserved among species.

...To assess alternative splicing patterns as well as transcription levels, both groups performed high-throughput sequencing of messenger RNA. They extracted RNA from a large array of organs of different vertebrate species, including frogs, chickens, primates, and humans. “It’s a massive amount of data,” said Cooper.

Blencowe’s team showed that the species-specific alternative splicing changes tended to be driven by differences in the transcripts themselves, which carry a splicing code that guides the splicing machinery—rather than differences in the splicing machinery. For example, human transcripts expressed in mouse cells exhibited human, not mouse, splicing patterns, despite being spliced by mouse machinery.

“These are very important papers that provide for the first time a large-scale view of the evolution of alternative splicing in vertebrates,” said Brent Graveley, professor of genetics and developmental biology at the University of Connecticut, who was not involved in the research. “They demonstrate how dramatically rapidly alternative splicing evolves, and suggest that it might play a role in speciation.”

The incredible capacity for alternative splicing could enable cells to try-out new versions of proteins without risking the complete loss of the originals, said Burge. Of course, if a new version then offers an advantage, the associated sequence changes to the splicing code will be selected for. “It is certainly an attractive model, and we think it is what’s going on,” said Burge. _TheScientist

This remarkably rapid and competitive evolutionary activity is taking place within each cell of almost every tissue inside your body.

Not only does this epigenetic process provide more reasons for differences between species, but it also likely provides more reasons for differences between sub-species. It will probably also eventually reveal significant differences in gene expression between identical twins.

A number of other genetic and epigenetic processes such as copy number variants, transposable elements, non-coding RNAs, non-coding DNAs, unique mutations (each person has about 100 unique mutations in his genome), etc. -- and more to be discovered -- have already provided us with reasons why two individuals with very similar DNA can easily develop significant differences in gene expression.

The alternative splicing mechanisms being elaborated in the two studies above, provide another very powerful source of difference in gene expression -- not only between individuals, but also between body tissues within the same individual. This evolutionary mechanism even introduces differences in gene expression between different cells of the same tissue type.

Biology just keeps getting more and more interesting all the time.