Nav: Home

Study finds convergent evolution of gene regulation in humans and mice

January 18, 2018

Organisms that aren't closely related may evolve similar traits as they adapt to similar challenges. It's called convergent evolution, and familiar examples include the wings of birds, bats, and insects, and echolocation in bats and dolphins. Now, molecular biologists have found evidence of convergent evolution in an important mechanism of gene regulation in humans and mice.

The new study, published January 15 in Proceedings of the National Academy of Sciences, was led by researchers at UC Santa Cruz and the University of Rochester Medical Center. They described a complex system that regulates the same genes in the same way in both species, yet evolved independently in the two lineages.

In both cases, the regulatory system involves noncoding RNA (sequences not translated into protein molecules) with origins in DNA segments randomly inserted into the genome by "jumping genes" (retrotransposons).

"This study highlights the importance of noncoding RNA and transposable elements in the regulation of gene expression and in the evolution of gene expression networks in mammalian genomes," said coauthor Manuel Ares, professor of molecular, cell, and developmental biology at UC Santa Cruz.

Only about 2 percent of the human genome is copied into messenger RNA molecules to code for the proteins that run the main processes in all cells. Most of the rest of the genome is transcribed into noncoding RNA whose function is largely unknown but which is suspected of playing a variety of roles in gene regulation and evolution.

Many of these noncoding RNAs are copied from repeated DNA sequences called short interspersed nuclear elements (SINEs). Once transcribed into RNA, they can be copied back into DNA and "pasted" into the genome at new locations in a process called retrotransposition. Sometimes these new copies land in or near genes and can damage them. Other times they can add new properties to the gene.

In the human genome, the major SINE family is made of so-called "Alu elements." There are more than 1 million copies of Alu, comprising more than 10 percent of human DNA, scattered throughout the genome, and some of them are likely still able to jump to new locations.

The mouse genome, however, doesn't have Alus; instead it has a distinct set of SINEs called B/ID elements. Different mammalian genomes have different SINEs because periodic bursts of retrotransposition by different SINEs continued to occur after the separation of different species from their last common ancestors. In the case of human and mouse, their lineages diverged about 90 million years ago.

"Surprisingly, when the mouse and human genomes were compared, the locations of SINEs were very similar, even though the SINEs themselves and the events that placed them at those locations were very different," Ares said. "We wondered what could explain this apparent convergence of SINE insertion in two independently evolving genomes."

Lynne Maquat's lab at the University of Rochester found that SINEs that land in the part of the gene encoding the tails of the messenger RNA (called the 3-prime untranslated region or 3'-UTR) bring the mRNA under the control of a protein called Staufen, which down-regulates expression of the gene by a process called "Staufen-mediated decay" or SMD. Individual examples of SINE-mediated SMD were previously documented in both human and mouse cells, in each case with different SINEs.

Since the modern SINEs in the human and mouse genomes were not in the common ancestor, all of the changes in gene expression that depend on SINEs must have occurred after humans and mice separated, and not in their common ancestor.

"Normally we think of important gene expression control systems as having evolved long ago, but for regulation by SINE-mediated SMD, this cannot be the case," Ares explained. "The question we asked was: Are there any cases where the same gene in mouse and human have been brought under SINE-mediated SMD, albeit using different SINEs at some point during the separate evolutionary histories of mice and men? If so, how many? And how common is convergent evolution of gene regulatory networks? How often do SINEs play a role in critically altering gene expression control?"

These questions were explored in a collaboration between the Rochester and UCSC labs, in which muscle precursor cells (myoblasts) from both organisms were analyzed to identify gene pairs (the mouse and human gene coding for the same protein) that had a SINE inserted in the mRNA tail and were under control of Staufen. Examples of such gene pairs in numbers greater than expected by chance would signal the possibility of convergent evolution of the Staufen regulatory network in myoblasts, where SMD is known to be important for gene control.

In myoblasts, the researchers were able to detect 24 genes that are both regulated by Staufen and have species-specific SINEs. This is a minimum number of potentially convergent pairs because not all genes are expressed in myoblasts, Ares noted. Additional experiments in the paper confirm the role of the SINE (by removing it and showing the mRNA becomes stable and insensitive to the presence of Staufen) for two gene pairs.
-end-
In addition to Ares and Maquat, the authors of the paper include first author Bronwyn Lucas, Hana Cho, and Keita Miyoshi at the University of Rochester; Eitan Lavi and Liran Carmel at the Hebrew University of Jerusalem; Lily Shiue and Sol Katzman at UC Santa Cruz; and Mikiko Siomi at the University of Tokyo.

University of California - Santa Cruz

Related Dna Articles:

Penn State DNA ladders: Inexpensive molecular rulers for DNA research
New license-free tools will allow researchers to estimate the size of DNA fragments for a fraction of the cost of currently available methods.
It is easier for a DNA knot...
How can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of biological systems?
How do metals interact with DNA?
Since a couple of decades, metal-containing drugs have been successfully used to fight against certain types of cancer.
Electrons use DNA like a wire for signaling DNA replication
A Caltech-led study has shown that the electrical wire-like behavior of DNA is involved in the molecule's replication.
Switched-on DNA
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.
Researchers are first to see DNA 'blink'
Northwestern University biomedical engineers have developed imaging technology that is the first to see DNA 'blink,' or fluoresce.
Finding our way around DNA
A Salk team developed a tool that maps functional areas of the genome to better understand disease.
A 'strand' of DNA as never before
In a carefully designed polymer, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA.
Doubling down on DNA
The African clawed frog X. laevis genome contains two full sets of chromosomes from two extinct ancestors.
'Poring over' DNA
Church's team at Harvard's Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School developed a new electronic DNA sequencing platform based on biologically engineered nanopores that could help overcome present limitations.

Related Dna Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...