[GRG] Non-coding DNA may have applicability in tissue regeneration

http://ift.tt/1jQQRGQ

New functions for ‘junk’ DNA?

Non-coding DNA sequences found in all plants may have undiscovered
roles in basic plant development and response to the environment

IMAGE: This image shows the evolutionary relationships among the
species analyzed for conserved non-coding sequences. ‘Myr’ stands
for million years ago. Ellipses are approximate times of whole-
genome duplications.

DNA is the molecule that encodes the genetic instructions enabling
a cell to produce the thousands of proteins it typically needs. The
linear sequence of the A, T, C, and G bases in what is called
coding DNA determines the particular protein that a short segment
of DNA, known as a gene, will encode. But in many organisms, there
is much more DNA in a cell than is needed to code for all the
necessary proteins. This non-coding DNA was often referred to as
“junk” DNA because it seemed unnecessary. But in retrospect, we did
not yet understand the function of these seemingly unnecessary DNA
sequences.

We now know that non-coding DNA can have important functions other
than encoding proteins. Many non-coding sequences produce RNA
molecules that regulate gene expression by turning them on and off.
Others contain enhancer or inhibitory elements. Recent work by the
international ENCODE (Encyclopedia of DNA Elements) Project (1, 2)
suggested that a large percentage of non-coding DNA, which makes up
an estimated 95% of the human genome, has a function in gene
regulation. Thus, it is premature to say that “junk” DNA does not
have a function—we just need to find out what it is!

To help understand the importance of this large amount of non-
coding DNA in plants, Diane Burgess and Michael Freeling at the
University of California, Berkeley have identified numerous
conserved non-coding sequences (CNSs) of DNA that are found in a
wide variety of plant species, including rice, banana, and cacao.
DNA sequences that are highly conserved, meaning that they are
identical or nearly so in a variety of organisms, are likely to
have important functions in basic biological processes. For
example, the gene encoding ribosomal RNA, an essential part of the
protein-synthesizing machinery needed by cells of all organisms, is
highly conserved. Changes in the sequence of this key molecule are
poorly tolerated, so ribosomal RNA sequences have changed
relatively little over millions of years of evolution.

To identify the most highly conserved plant CNSs, Burgess and
Freeling compared the genome (one copy of all the DNA in an
organism) of the model plant Arabidopsis, a member of the mustard
family, with the genome of columbine, a distantly related plant of
the buttercup family. The phylogenetic tree (see figure) shows the
evolutionary relationships among the dicot (yellow) and monocot
(blue) species they studied. Branch points represent points of
divergence of two species from a common ancestor. Sequences in
common between these two plants, which diverged over 130 million
years ago, are likely to have important functions or they would
have been lost due to random mutations or insertions or deletions.

They found over 200 CNSs in common between these distantly related
species. In addition, 59 of these CNSs were also found in monocots,
which are even more distant evolutionarily, and these were termed
deep CNSs. Finally, they showed that 51 of these appear to be found
in all flowering plants, based on their occurrence in Amborella, a
flowering plant that diverged from all of the above plants even
before the monocot-dicot split (see figure).

So what could be the function of these deep CNSs? We can get clues
by analyzing the types of genes with which these CNSs are
associated. The researchers found that nearly all of the deep CNSs
are associated with genes involved in basic and universal
biological processes in flowering plants—processes such as
development, response to hormones, and regulation of gene
expression. They found that the majority of these CNSs are
associated with genes involved in tissue and organ development,
post-embryonic differentiation, flowering, and production of
reproductive structures. Others are associated with hormone- and
salt-responsive genes or with genes encoding transcription factors,
which are regulatory proteins that control gene expression by
turning other genes on and off.

In addition, they showed that these CNSs are enriched for binding
sites for transcription factors, and propose that the function of
some of this non-coding DNA is to act as a scaffold for
organization of the gene expression machinery. The binding sites
they found are known sequences implicated in other plants as
necessary for response to biotic and abiotic stress, light, and
hormones. Furthermore, they discovered that a number of the CNSs
could produce RNAs that have extensive double-stranded regions.
These double-stranded regions have been shown to be involved in RNA
stability, degradation, and in regulation of gene expression.
Twelve of the most 59 highly conserved CNSs are associated with
genes whose protein products interact with RNA. Clearly, these DNA
sequences are not merely “junk!”

Now that Burgess and Freeling have identified the most highly
conserved non-coding DNA sequences in flowering plants, future
scientists have a better idea of which regions of the genome to
focus on for functional studies. Do the predicted transcription
factor-binding sites actually bind known or novel transcription
factors? Do CNSs organize or regulate the gene expression
machinery? Do CNSs encode RNAs that regulate fundamental processes
in plants? The answers to these and many related questions will be
easier to answer now that we have this set of deep CNSs that are
likely to play important roles in basic cellular processes in
plants.

###

References

(1) National Human Genome Research Institute (see
http://ift.tt/OZAarF)

(2) Genome Research, Vol. 17, June 2007, special issue on ENCODE.

Author:
Gregory Bertoni
gbertoni@aspb.org
Science Editor, The Plant Cell
American Society of Plant Biologists

This work was supported by The National Science Foundation
(IOS1248106).

Full citation: Burgess, D., and Freeling, F. (2014). The most
deeply conserved noncoding sequences in plants serve similar
functions to those in vertebrates despite large differences in
evolutionary rates. Plant Cell 10.1105/tpc.113.121905.

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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