RNA discovery

In the three decades since RNA was first sequenced in 1975, scientists have been intrigued by how the genome relates to life, studying has been limited to looking at only one gene at a time. Now Erik Sperling GRAD ’11, a graduate student in the Yale Geology and Geophysics Department, and his colleagues have changed that. Staff reporter Rachel Gilmore investigates.

In research published Tuesday, the team reported their findings that microRNA or miRNA, single-stranded regulators of gene expression, can help us chart evolutionary history — and they used it to correct a misunderstood evolutionary fact.

It began in 2007 with the arrival of Roche 454, a machine that can make 400,000 sequences of long base pairs quickly, enabling researchers to study 20 million nucleotides at a time in a computer gene matrix.

At the time, Sperling and Kevin Peterson, a researcher at Dartmouth, were intrigued by the discrepancy between fossil records and previous gene sequencing of annelids, the class of organisms including segmented worms like leeches. While miRNA had been previously studied in the context of genetics and development, the researchers came up with the idea to use it as a marker of evolution, Sperling recalled.

The researchers extracted miRNA from annelids, created libraries of the samples at Dartmouth, and finally had the RNA sequenced on the 454 machine.

The results of the study confirmed the order in which these groups of annelids appeared in the fossil records — whereas previous molecular schemes for these early invertebrates disagreed with the fossil record, said Derek Briggs, Sperling’s supervisor on the project.

Previous genetic sequencing had indicated that sipunculidea, the class that includes peanut worms, were derived annelids. Fossil records — and now, miRNA studies — indicate that the two are related, but that sipunculidea were never annelids, Sperling said.

MiRNA analysis is a more dependable indicator of common ancestors than mutation analysis, a technique that involves examining mutations in a single gene, because organisms continue to acquire miRNA throughout evolution and do not lose old miRNA, Jakub Vinther, co-author on the study, said. Mutation analysis has been known to turn up false connections if the organisms in question have a high rate of mutation, he added. For instance, only one gene mutation separates the genome of a human and that of a fruit fly, but the two have not shared a common ancestor in 600 million years.

Mutational analysis would be a relatively ineffective way to study the evolutionary history of annelids, he explained.

“The problem with annelids is that they all evolved from one another a long time ago in a very brief period of time, not allowing for many genetic mutations,” he said.

Briggs said Sperling’s combination of geological fossil records and cutting-edge genetic techniques, especially the novel use of microRNA as an evolutionary marker, makes the finding methodologically important.

“Erik is a geologist, first and foremost, but is remarkable because he is truly interdisciplinary,” Briggs said of his research.

The results of this study will have long-term influence on how evolution and genetics are studied, Vinther said. He added that the potential of miRNA is vast and will be important in understanding human disease and the function of bodily organs.

The study was published online on Sept. 15 in the Proceedings of the Royal Society B.

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