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Study Suggests Piwi-Interacting RNAs Expanded Rapidly in Mammals

NEW YORK (GenomeWeb News) – A new phylogenetic study scheduled to appear online this week in the Proceedings of the National Academy of Sciences indicates that Piwi-interacting RNAs are evolved through rapid recombination and expansion in mammals.

Researchers from the University of Michigan compared piRNA clusters in the rat and mouse genomes to those in human, dog and cow genomes. Their results suggest that more than 40 percent of rodent piRNA clusters arose since rodent and primate lineages diverged — a more rapid expansion than any known for mammalian protein-coding genes. That pattern was even more pronounced for clusters in non-protein coding parts of the genome. On the other hand, the team did not find any cases of piRNA cluster loss.

Lead author Raquel Assis, a graduate student in evolutionary geneticist Alexey Kondrashov's lab at the University of Michigan, told GenomeWeb Daily News that the rapid piRNA expansion, coupled with a lack of cluster losses, suggests piRNA clusters are under positive selection.

Although researchers have not ruled out other functions for the small, non-coding RNAs, piRNAs are thought to silence transposons in mammals. These 30 nucleotide RNAs tend to occur in clusters in the genome that seem to be transcribed as units before being processed into piRNAs.

While previous research suggests microRNAs evolve slowly, little-to-no research has been done to address piRNA evolution — though, on a small scale, there is some evidence suggesting their sequences change about as often as other non-functional sequences in the genome.

In an effort to understand the large-scale evolution of piRNAs, Assis and Kondrashov evaluated 140 rodent piRNA clusters as well as the protein-coding sequences flanking them, using pairwise alignments to compare rat and mouse piRNA regions with those in human, dog, and, in some cases, cow genomes.

Of the 140 clusters they looked at, 103 did not overlap with protein-coding genes. All 37 clusters that did overlap appeared to be ancestral sequences, since they were present in rat, mouse, and human genomes. On the other hand, when the duo evaluated the intergenic piRNA clusters, they found that just 43 of the clusters were ancestral, while 60 were acquired relatively recently — 14 since rats and mice diverged and 44 after the rodent-primate divergence but before the rat-mouse split.

When the researchers randomly selected 103 intergenic sequences that resembled clusters but did not code for piRNAs, they reported that all but seven were ancestral, suggesting most intergenic regions do not undergo changes as rapidly as those observed in the intergenic piRNA clusters.

Based on their analysis of nine of the clusters that arose after the rat-mouse evolutionary split, the researchers concluded that piRNA clusters probably arose and expanded rapidly through recombination and long sequence insertions in a pattern similar to the duplications observed for some protein-coding sequences.

"The rate of piRNA cluster expansion is higher than that of any known gene family and, in contrast to other large gene families, there was not a single cluster loss," Assis and Kondrashov wrote. Based on this and other evidence, the team concluded that piRNAs are likely under positive selection.

Still, they noted that more wild type rat and mouse genomes will have to be investigated before this can be confirmed. And on a small scale, piRNA evolution was not as rapid as it is on a large scale. Instead, the researchers reported, small scale evolutionary rates were similar to those observed in other mammalian sequences.

"If piRNAs are indeed involved in transposons silencing, it is natural to assume that selection for cluster acquisitions is caused by an arms race between expanding families of mammalian transposons and piRNA clusters," Assis and Kondrashov concluded.

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