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Tiny molecules drove the evolution of the vertebrates

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Blogging on Peer-Reviewed ResearchThe spinal column that runs down your back is an identity badge that signifies your membership among the vertebrates – animals with backbones. Vertebrates have arguably the most complex bodies and genomes of any animal group and certainly, our lineage has come a long way from its last common ancestor.

TigerThe closest evolutionary cousins of the vertebrates are simple aquatic creatures such as the jawless lancelets and the sac-like, immobile sea squirts. How did these simple body plans diversify into the vast array of sophisticated forms wielded by today’s fish, amphibians, reptiles and mammals?

Gene number

Many scientists have suggested that the answer lies in the number of our genes. At three different points, the vertebrate genome (its full suite of genes) experienced a massive jump in size as huge chunks of genes – possibly the entire lot – were duplicated. The first of these coincided with the origins of the group itself and the second happened alongside the rise of the first jawed fish, setting them and their descendants aside from more ancient jawless forms like the lampreys.

So far, there seems to be a tidy connection between gene number and complexity, but the third round of duplication is a bit of a stumbling block. It happened at some point during the evolution of the bony fishes and while this group proceeded to radiate into a multitude of different shapes, their basic body plan stayed essentially the same. No big jump in complexity there.

Indeed, as the full genome sequences of more and more species are revealed, it’s becoming clear that the basic genetic toolkit that controls the development of animal bodies is remarkably consistent across the kingdom. Even the genome of a sea anemone, one of the simplest and most ancient animals on Earth, is strikingly similar to that of vertebrates.

In this light, it’s looking increasingly unlikely that the advent of new genes can account for the large rise in vertebrate complexity. Now, Alysha Heimberg and colleagues from Dartmouth College have proposed a new theory, centred around tiny molecules called microRNAs.

MicroRNAs

First, a quick crash course in molecular biology. Genes are made up of stretches of DNA, which acts as a sort of molecular code To be of use, the code is read and transcribed into a related molecule called RNA. This transcript is used as instructions for building proteins that go on to do useful jobs around our cells.

MicroRNABut large reams of RNA are never translated into proteins. Vertebrates genomes in particular are rife with these non-coding stretches, and we have over 10 times more of them than invertebrates like worms and flies. These stretches of code are often labelled as “junk” but it’s an unfair and inaccurate term. It is now clear that they have very important roles indeed.

MicroRNAs are a particular group of non-coding RNA that has captured the interests of scientists. They are tiny, much smaller than the average piece of protein-coding RNA, and the equivalent of a long word nestled within a single page in a shelf of books. These minute molecules control other genes and carefully determine which are switched on and which are turned off.

Recently, they have been implicated in the development of cancer and heart disease but Heimberg has assigned them with the altogether more congenial role of fuelling the rise of vertebrate complexity.

Organisation vs. recruitment

Our repertoire of microRNAs far outstrips those of invertebrates, and over 50 families arose during the course of vertebrate evolution. Once added, new microRNAs are incredibly stable over time and unlike other parts of the genome, they are very rarely altered or lost. These traits allowed Heimberg to create an accurate microRNA family tree, charting the addition of these controlling molecules as the vertebrate lineage rose and branched out.

To do this, Heimberg scoured the genomes of several vertebrates for microRNA sequences. She looked at species from humans to chickens to sharks, along with some of our evolutionary cousins – the lancelets and sea squirts.

Heimberg found that the genomes of vertebrates have been massively fortified with microRNAs. A massive number of new families exploded into being during a short span of time when the vertebrate dynasty first evolved some 500 million years ago. This rapid acquisition occurred slightly ahead of the gene-duplication event, which then served to increase the diversity of microRNAs within each family.

PythonThis key period marked the height of microRNA innovation and the vertebrates have never since acquired new families so quickly at any other point during their history. To Heimberg, the timing is no coincidence. Many of these new microRNAs are also found in parts of the body like the liver and pancreas that are unique vertebrate inventions, or organs like the brain that are considerably more sophisticated than those of their invertebrate counterparts.

It seems then, that the complexity of the vertebrate body stems from ancient innovations in the control of genes rather than the bulk addition of new ones. Our genes instruct a workforce of proteins, and rather than adding more staff, we simply redeployed the existing personnel in new and ground-breaking ways.

Reference: Heimberg, A.M., Sempere, L.F., Moy, V.N., Donoghue, P.C., Peterson, K.J. (2008). MicroRNAs and the advent of vertebrate morphological complexity. Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0712259105

Images – tiger by Anant



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