Genes Have Help in Determining Our Traits

Yale scientists find that a type of RNA together with a common protein to protect organisms from harmful genetic variations
Monday, 27 December 2010

For decades, biology textbooks have been clear – our traits are the product of our genes. But a new study by Yale University researchers published Dec. 26 in Nature Genetics suggests another mechanism can regulate variations of traits even in genetically identical individuals.

A particular type of RNA works in concert with a common protein to protect organisms from harmful genetic variations without the help of genes, reports Haifan Lin, director of the Yale Stem Cell Center, professor of cell biology and genetics and senior author of the paper.

“This mechanism may help explain how ordinary cells such as fibroblasts can be converted to stem cells and why some cancers develop at random,” Lin said.

The theory that factors other than genes are responsible for an organism’s traits, or phenotype, has been around for almost 70 years but has only gained steam in the past decade. For instance, cloned animals are often born with different colours than the animals that are the source of their DNA. But what causes these changes remained unclear.

About a decade ago, scientists found that a noticeable percentage of flies lacking a protein called Hsp-90 ended up with bizarre and random abnormalities such as legs growing where eyes should be. It seemed clear that Hsp-90 protected an organism against harmful genetic variations in its genome. Yet, since Hsp-90’s role is to mobilize other molecules to respond to stress, researchers suspected other factors were involved.

One school of thought suspected that Hsp-90 prevents the display of random abnormalities by suppressing the activities of “jumping genes” that can relocate to other areas of the genome and cause mutations. However, the Yale researchers report that their work with flies shows that a type of small RNA called Piwi-interacting RNA, or piRNA, acts in concert with Hsp-90 and another molecule to prevent both the creation of variants and the activation of existing genetic variants. Genes do play a role in protecting against harmful variations but probably work through actions of the molecules piRNA and Hsp-90.

Lin, who studies piRNAs in reproductive cells and stem cells, says that the variations in levels of Hsp-90 and piRNAs among individual cells of the same type might explain why a small number of ordinary cells can be reprogrammed into stem cells and also why harmful mutations are created in some cancers.

“This study shows that we still have a lot to learn about the most basic principles of gene regulation,” Lin commented.

“Studies of this kind may provide missing puzzles in our understanding of normal development and malignancies.”

Source: Yale University
Contact: Bill Hathaway

Reference:
Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation
Vamsi K Gangaraju, Hang Yin, Molly M Weiner, Jianquan Wang, Xiao A Huang & Haifan Lin
Nature Genetics, 26 December 2010, doi:10.1038/ng.743
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MicroRNAs Emerged Early in Evolution

MicroRNAs are found in animals that appeared a billion years ago Thursday, 02 October 2008 MicroRNAs, the tiny molecules that fine-tune gene expression, were first discovered in 1993. But it turns out they've been around for a billion years. Evidence reported in Nature on October 1 by scientists in the lab of Whitehead Member and Howard Hughes Medical Institute investigator David Bartel provides a window into the early evolution of these key regulators, placing their origin within the earliest of animal lineages. The research also suggests that microRNAs present early on have undergone extensive changes, which likely have altered their functions across various lineages. "This is the first evidence that microRNAs were present within the earliest animal lineages and are not just characteristic of more complex animals," says Andrew Grimson, a postdoctoral fellow in Bartel's lab. Scientists knew that microRNAs existed within bilaterians, an evolutionary group that includes everything from worms to fruit flies to humans, he explains. "Remarkably, we discovered their presence within sponge, a member of the earliest diverging group of animals." The scientists used high-throughput sequencing to probe samples from animals that diverged before the origin of bilaterian animals. The sponge (Amphimedon queenslandica) represents a group of animals that split off in evolution very early, whereas the starlet sea anemone (Nematostella vectensis) split off more recently. The sequences of microRNAs within each lineage were different from each other, suggesting that microRNA functions are almost certainly very different in these different lineages. "In a relatively narrow spectrum of evolution microRNAs are often conserved," says Grimson. "But in a broader spectrum they have completely changed. This suggests that microRNA evolution is more flexible and may be evolving more rapidly than suspected." Researchers also pinpointed piRNAs, another class of small RNAs, among these two species. Although less is known about piRNAs, they characteristically have longer sequences than microRNAs and are thought to dampen the activity of transposons — chunks of DNA that can move around the genome, causing mutations. "It appears that both microRNAs and piRNAs have been available to shape gene expression throughout the evolution of animals and perhaps even helped to usher in the era of multicellular animal life," says David Bartel. Reference: The Early Origins and Evolution of microRNAs and piRNAs in Animals Andrew Grimson, Mansi Srivastava, Bryony Fahey, Ben J. Woodcroft, Nicole King, Bernard M. Degnan, Daniel S. Rokhsar, David P. Bartel Nature advance online publication 1 October 2008, doi:10.1038/nature07415 See also: New Research Shows MicroRNAs Emerged Early in Evolution HHMI NEWS – October 01, 2008 ......... ZenMaster

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New group of tiny RNAs - the piRNAs

New group of tiny RNAs play a big role in controlling genes Thursday, 25 October 2007 A study by researchers at the Yale Stem Cell Center for the first time demonstrates that piRNAs, a recently discovered class of tiny RNAs, play an important role in controlling gene function, it was reported this week in Nature. Haifan Lin, director of the stem cell center and professor of cell biology at Yale School of Medicine, heads the laboratory that originally identified piRNAs. Derived mostly from so-called “junk DNA,” piRNAs had escaped the attention of generations of geneticists and molecular biologists until last year when Lin’s team discovered them in mammalian reproductive cells, and named them. The lab’s current work suggests that piRNAs have crucial functions in controlling stem cell fate and other processes of tissue development. In this study Lin and his Ph.D. student, Hang Yin, discovered more than 13,000 Piwi-associated piRNAs in fruit flies. One particular piRNA, they found, forms a complex with the protein known as Piwi, which then binds to chromatin, a strategic region in the genome that regulates the activity of the gene. Chromatin’s role is to package DNA so that it will fit into the cell, to strengthen the DNA to allow cell division, and to serve as a mechanism to control gene expression. “This is important in maintaining self-renewal of stem cells,” Lin said. “These small RNAs might provide new tools to harness the behaviour of stem cells and other biological processes related to diseases.” “This finding revealed a surprisingly important role for piRNAs, as well as junk DNA, in stem cell division,” Lin said. “It calls upon biologists to look for answers beyond the one percent of the genome with protein coding capacity to the vast land of junk DNA, which constitutes 99 percent of the genome.” ......... ZenMaster

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For more on stem cells and cloning, go to CellNEWS at http://www.geocities.com/giantfideli/index.html

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