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DNA Shape Is Constrained By Evolution: Structural Approach To Exploring DNA

A team led by researchers from Boston University and the National Institutes of Health has developed a new method for uncovering functional areas of the human genome by studying DNA’s three-dimensional structure — a topographical approach that extends the more familiar analysis of the sequence of the four-letter alphabet of the DNA bases.

Unlike the well-understood genomic sequences that code for proteins and comprise about two percent of the human genome, the remaining 98 percent is the non-coding portion, which encodes many functions. However, little is known about how this functional non-coding information is specified.

In a study which appears March 12 in the online edition of Science, the researchers focused on examining the non-coding regions of the genome for areas that are likely to play a key role in human biological function.

To do this, the researchers developed a method which incorporates information about the structure of DNA to compare sequences of genomes from humans and 36 mammalian species that included the mouse, chimpanzee, elephant and rabbit.

By examining the shapes, grooves, turns and bumps of the DNA that comprises the human genome, the team discovered that 12 percent of the human genome appears to be constrained by evolution. That’s double the six percent detected by simply comparing the linear order of DNA nucleotides (A, T, G, and C, the familiar letters that make up the genome). The huge increase stems from finding some DNA sequences that differ in the order of nucleotides, but have very similar topographical shapes, and so may perform similar functions.

They went on to show that the topographically-informed constrained regions correlate with functional non-coding elements better than constrained regions identified by nucleotide sequence alone.

“By considering the three-dimensional structure of DNA, you can better explain the biology of the genome,” said Thomas D. Tullius, Boston University professor of chemistry who has spent more than 20 years developing ways to map the structure of the human genome. “For this achievement Stephen Parker, a Boston University graduate student, deserves much of the credit for his development of the algorithm that incorporated DNA structure into evolutionary analysis.”

Bringing a molecular biologist’s point of view and expertise in comparing the genomes of different species was Elliott Margulies, an investigator at NHGRI’s Genomic Technology Branch. “Proteins that influence biological function by binding to DNA recognize more than just the sequence of bases,” he said. “These binding proteins also see the surface of the DNA molecule and are looking for a shape that allows a lock-and-key fit.”

In their Science paper the researchers also explored how small genetic changes, or variations, known as SNPs (Single Nucleotide Polymorphisms) could prompt structural changes that might lead to disease. In studying these mutations from a database of 734 non-coding SNPs associated with diseases, such as cystic fibrosis, Alzheimer’s disease, and heart disease, they found that disease-associated SNPs produced larger changes in the shape of DNA than SNPs not associated with a disease.

The new research findings on evolutionary conservation of DNA structure stem from recent progress in analyzing the functional elements in a representative fraction of the human genome. That study, known as ENCODE (ENCyclopedia of DNA Elements), organized by the National Human Genome Research Institute (NHGRI), challenged the traditional view of the human genetic blueprint as a collection of independent genes. Instead, researchers found a complex network of genes, regulatory elements, and other DNA sequences that do not code for proteins.

Researchers say DNA sequence is not always a good indicator of function. They found that very similar DNA sequences may assume very different topographical shapes, which can have a major impact on their function or lack of function. On the other hand, different DNA sequences may assume very similar topographical shapes and perform very similar functions. So, in many instances, DNA structure may be a better predictor of function than DNA sequence.

The study determined, for the first time, where many types of functional elements are located, how they are organized, and how the genome is pervasively made into RNA. The current research on genome structure and function is based on some of the ENCODE findings, noted Tullius, whose work in developing the new technology was funded through the ENCODE project.

In addition to Tullius and Margulies, the other authors of theScience paper are Stephen C.J. Parker and Loren Hansen, both BU graduate students in bioinformatics, and Hatice Ozel Abaan, a technician in Margulies’ laboratory.

Short URL: http://chandadavis.net/?p=1396

17 Comments for “DNA Shape Is Constrained By Evolution: Structural Approach To Exploring DNA”

  1. Chanda Davis ---5th Period

    1. This article is about DNA.
    2. The artilce states that scientist have come with a three letter structure for analyzing DNA.
    3. Scientists are comparing human DNA to other species.
    4. They are trying to find a lock-and-key fot for DNA.
    .5. This study os done through the ENCODE project.

  2. Chase Massey-5th Period

    1. twelve percent of the human genome appears to be constrained by evolution
    2. some DNA sequenses differ in the order of nucleotides
    3. DNA have similar shapes and may perform similar functions
    4. A, T,G, and C are the fimiliar lettersthat make up the human genome(the 4 letter alphabet of the DNA bases)
    5. by consisering the 3-dimensional structure of DNA, you can better explain the biology of the genome

  3. 1 this article is about dna
    2 the team was lead by boston university
    3 the team discverd that 12 percent of the human genome appears to be constrained by evalution
    4 in there science paper the reserchers explord how small genetic changes could prompt structual changes tha tmight lead to deseases

    5 the studey determand for the first time where many tipes of functual elaments are located

  4. 1.The artical is about DNA.
    2.Geonome is called RNA.
    3.DNA have the same shape.
    4.12 percent of our DNA’s geonome is revolved.
    5.They tried to find a lock for DNA.

  5. 1. 12 percent of the humane genome is constrained by evolution.
    2. Scientists are comparing our DNA to other species.
    3. Small genetic changes are called SNPs.
    4. They are trying to find a lock and key for our DNA.
    5. The study is known as ENCODE

  6. Steven Owens 5th

    1.this articale is about DMA
    2.. 12 percent of the human genome is constraind by evolution.
    3.the remaining 98 percent is the noncoding portion, which encodes many function
    4 They found that very similarDNA sequences may assume very different topographi shape

  7. chase lovell 5th perieod

    1.Its about DNA
    2.12 percent pof humans contrain genome
    3. Small genetic changes are called SNP
    4.Geonome is called RNA
    5.98 percent remaing noncoding portions,which encodes many functions.

  8. Amari Anderson period 1

    1. 12 percent of human’s genomes are constrained by evolution.

    2. They found that DNA could have very different shapes.

    3. The team that researched is from boston university.

    4. Another name for genome is GNA.

    5. The article is about dna.

  9. Ebone' Yarbrough--5th period

    DNA have similar shapes and may perform similar functions.Another name for genome is GNA. Genome is called RNA.Scientists are comparing human DNA to other species.Researchers say that DNA sequence is not always a good indicator of function.12 percent of human’s genomes are constrained by evolution.98 percent remaining non-coding portions,which encodes many functions.The study is known as ENCODE.The team that researched is from Boston university.

  10. 1. This article is about DNa

    2. 12% of the human genome is constraind by evolution.

    3. DNA have similar shapes and may perform similar functions

    4. the remaining 98 percent is the noncoding portion, which encodes many function

    5. Scientists are comparing human dna to other dna, which they talk about in this article

  11. Avery Wilson 4th per.

    Scientists SAY that 12 percent of the human genome is constrained by evolution.
    Geonome is made into RNA.
    DNA sequence isnt a good indicator of function.
    Scientists are comparing human DNA to 36 other species.
    They are trying to find a lock for DNA.

  12. alex 4th period

    1 this article talks about DNA
    2 Twelvepercent of our DNA’s geonome is revolved.
    3 Scientiss have come up with a 3 letter structure for DNA.
    4 the other 98 percent is the noncoding portion
    5 Another name for a genome is a GNA.

  13. TARRELL CLEMONS 1st PERIOD 3-27-10

    1 this article talks about DNA
    2 Twelvepercent of our DNA’s geonome is revolved.
    3 Scientiss have come up with a 3 letter structure for DNA.
    4 the other 98 percent is the noncoding portion
    5 Another name for a genome is a GNA.
    you happy ms. davis !!!!!!!!!!!!!.

  14. Julia Harrelson

    1. DNA shApe is constrained by evolution: structural approach to exploring DNA.
    2. A team led by research from Boston Univeristy &The National Insitutes of Health has been developing a new method for uncovering funcitional areas of the humAn genome.
    3. A topogrphical approach is being used for the four letter sequence of the DNA bases.
    4. Genoomic sequences is a code for proteins.
    5. On March 12 in a article of Science reasearchers focused on examing the non-coding regions that likely to play a key role in human bilogical function.

  15. keenan drake 2nd

    1. this article is about dna
    2. the team was lead by boston university
    3. the team discverd that 12 percent of the human genome appears to be constrained by evalution
    4. in there science paper the reserchers explord how small genetic changes could prompt structual changes tha tmight lead to deseases
    5. the studey determand for the first time where many tipes of functual elaments are located

  16. Mauhaun Taheri

    1. The article is about DNA revolution in the human body.
    2.Some colleges have a new method for uncovering funcitional areas of the genome.
    3. studies show goweonome is made into RNA.
    4. About 12% of the haman body is evolution.
    5. Another name for genome is GNA.

  17. 1. Researchers are studying the structure of DNA and its coding and non-coding parts.
    2. 2 percent of the genomic sequence codes for proteins while the remaining 98 non coding percent encodes many other functions that are not specified.
    3. 12 percent of the human genome is constricted by evolution found by examination of the bumps, grooves, shapes and turns of DNA.
    4. SNPs are Single Nucleotide Polymorphisms. Which are small genetic variations.
    5. Researchers have found that DNA structure may be a better predictor of function that DNA sequence.
    5.

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