Ancestral genes take on new roles

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November 18, 2017 23:12

The scientists started out with the assumption that evolution is an economical process; if a gene loses its function, it may well be “recycled” for different purposes in the cell.

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genes biology 88

genes biology 88. (photo credit: )

There is a popular notion that monkeys or other animals and humans have many genes in common.

But these comparisons are sometimes misleading, “Humans and fish, for instance, share about 70% of their protein-coding genes, but only about 0.5% of an important class of regulatory genes – ones that give rise to so-called long non-coding RNAs, or lncRNAs,” according to Dr. Igor Ulitsky of the biological regulation department at the Weizmann Institute of Science in Rehovot.

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The lncRNAs (pronounced link-RNAs) have received little attention until recently. Not only are there as many as 20,000 lncRNA genes in the human genome – about the same number as the protein-coding ones – but the lncRNAs have lately been revealed to serve as master switches in a wide variety of biological processes, turning other regulatory genes on and off and controlling the fate of cells during fetal development, as well as cellular division and death in the adult organism.

In a study published recently in the journal Genome Biology, Ulitsky and his team – research students Hadas Hezroni, Gali Housman and Zohar Meir, and staff scientists Drs. Rotem Ben-Tov Perry and Yoav Lubelsky – managed to identify a class of mammalian lncRNAs that had evolved from more ancient genes by taking on new functions.

The scientists started out with the assumption that evolution is an economical process; if a gene loses its function, it may well be “recycled” for different purposes in the cell. The team members developed a series of algorithms that enabled them to find such “recycled” genes in the mammalian genome.

First, they identified nearly 1,000 genes that code for proteins in chickens, fish, lizards and other non-mammalian vertebrates, but not in humans, dogs, sheep and other mammals. The scientists hypothesized that at least some of these genes, after losing their protein-coding function, started manufacturing lncRNAs in mammals.

By comparing “gene neighborhoods” in the vicinity of lncRNAs and of genes that had stopped coding for proteins, the researchers revealed that indeed, about 60 lncRNA genes in mammals – or 2% to 3% of lncRNAs shared by humans and other mammals – appear to be derived from ancestral genes. Their genetic sequence is in some cases similar to that of the ancient genes, but they have lost their protein-coding ability.

“It is hard to know what caused these genes to lose their protein-coding potential more than 200 million years ago, when mammals evolved from their vertebrate ancestors,” Ulitsky said. “But the fact that these genes have been conserved in the genome for so long suggests that they play important roles in the cell.”

Identifying such “fossils” of protein-coding genes in the mammalian genome will promote further study of human lncRNAs and may ultimately help scientists understand what happens when their function is disrupted, he added. For example, lncRNAs help create different types of neurons in the fetal brain; their failure to properly determine the fate of these neurons may contribute to epilepsy. Because lncRNAs are involved in controlling cell division, their malfunction may be implicated in cancer. Finally, manipulating lncRNAs may make it possible to treat certain genetic disorders.

“In recent years, lncRNAs were found to be important for the activation or repression of genes relevant to a variety of disorders,” he concluded.

“It may one day be possible to treat these disorders by targeting the lncRNAs so as to reprogram entire gene regulatory networks. For example, in a study in mice, researchers at Houston’s Baylor College of Medicine had averted progression of Angelman syndrome, caused by mutations on chromosome 15, by silencing a particular lncRNA to unleash the expression of a gene it represses.”

WIKIPEDIA HAS SURPRISING POWER IN SCIENCE Wikipedia, the fifth most used website in the world, has had a profound impact on scientific literature, according to a recently released working paper at the Massachusetts Institute of Technology.

Technical innovation Prof. Neil Thompson and Douglas Hanley from the University of Pittsburgh commissioned graduate chemistry students to create new Wikipedia articles on scientific topics that have been missing from the online site. These newly created articles were then randomized, with half being added to Wikipedia and half being intercepted. The articles they uploaded got thousands of views per month; later investigation revealed that researchers writing in the scientific literature were more likely to use the words from the uploaded articles than the ones held back.

“Our research shows that scientists are using Wikipedia and that it is influencing how they write about the science that they are doing,” noted Thompson. “Wikipedia isn’t just a record of what’s going on in science, it’s actually helping to shape science.”

The authors find that, for a typical article in the field, Wikipedia is influencing usage of one word in every 300. The effect is also stronger for developing counties where scientists may have less access to traditional science journals.

“Public sources of scientific information such as Wikipedia,” said Thompson, “are incredibly important for spreading knowledge to people who are not usually part of the conversation. We hope that funding agencies take note,” said Hanley. “This is a very cost-effective way to enhance the dissemination scientific knowledge.”


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