Epic of Evolution  
 

“Mutations produced by transposons are a source of variation to drive the process of evolution."
~ Barbara McClintock, discoverer of transposons

“Evolution does not produce novelties from scratch: it works on what already exists. “
~ Ken Miller, Cell biologist

DNA is at the heart of biological evolution.

 

Tinkering with Evolution: Using Velcro to Simulate “Jumping Genes”

Tinkering with DNA: Using Velcro to Simulate “Jumping Genes”

For many people, one of the greatest challenges to understanding how the vast variety of life on Earth evolved is to understand how changes in DNA could create such complexity. If these changes were all due to random point mutations, then the probability of complex life forms would, for most people, seem intuitively to be vanishingly small. And intuition is right. Complex life forms do not arise from the accumulation of random point mutation. Instead, the kinds of changes that accelerate evolution are duplications and rearrangements of long stretches of DNA.

Hands on Activity by Catherine Russell, Ph.D.

Summary: Students will create a model of a DNA genome using Velcro.  Students will use this model to demonstrate mobile DNA and the role of mobility and duplication in evolution.  Students will move sections of "DNA" around the genome to simulate “jumping genes.”  This mobile DNA is what François Jacob in 1977 called “evolution by molecular tinkering.”  Jumping genes are an important source of genetic variation.  In creating genetic variation, mobile DNA is as important as point mutations, the more familiar concept of how DNA changes over time.

Grade level: 7-16

Time:  50 minutes

Prerequisite

Before doing this activity, students should have a general understanding that DNA stores genetic information in base pairs of nucleotides. Long sequences of these base pairs form genes, which in turn provide the information to encode RNA and subsequently proteins.

Student Learning Outcomes

  • Students will demonstrate how mobile DNA is an important source of evolutionary innovation. They will be able to contrast mobile DNA with point mutations as a source of genetic variation.
  • Students will be able to demonstrate that whole sections of DNA can be deleted, duplicated, inserted, and moved to other parts of the chromosome and even to other organisms via horizontal gene transfer.
  • Students will understand how changes in DNA affects evolution.
  • With a working understanding of the modular nature of DNA, students will have the intellectual tools to test “irreducible complexity,” the major idea from the Intelligent Design community used to discredit evolution by natural selection.

Introduction

DNA is at the heart of biological evolution.  Understanding how DNA changes over time is key to understanding how organisms change over time.  Up until recently, most people have understood that change in DNA has been attributed to single point mutations. Point mutations are changes in a single base pair of DNA.  However, point mutations account for only a fraction of variation in DNA.

The other important source of variation in DNA is movement of large sections of DNA.  These can be deletions, insertions, rearrangements and duplications.

This movement of DNA is sometimes called “evolutionary tinkering.” Evolutionary “tinkering” is the mixing and matching of different segments of DNA building blocks.  Evidence shows that this tinkering and movement of mobile genetic elements, a.k.a., “jumping genes,” is the source for much genetic novelty. These simple changes in DNA structure can cause big changes in an organism and hence in evolution.

For some people, the term “tinkering” is problematic because it implies a tinkerer, that is, some intelligence that “decides” which DNA gets mixed and matched.  However, the only “tinkerer” in evolution is the random movement of genes jumping around and between genomes.

“Evolution does not produce novelties from scratch: it works on what already exists. “
~ Ken Miller, cell biologist 

In addition to explaining the genetic basis of evolution, mobile DNA also explains another mystery, namely why the human genome contains so many noncoding regions of DNA. 

Note to the Instructor:

Because this activity is so easy to set up, it allows lots of time for rich discussion of the mechanism of jumping genes and their importance in evolution.

National Standards Addressed (NRC):

•        9-12: This activity directly addresses two of the major six content standards for life sciences education in grades 9-12: Molecular basis of heredity and Biological evolution.  Following is pertinent text from the National Science Education Standards of the National Research Council:

THE MOLECULAR BASIS OF HEREDITY

  • In all organisms, the instructions for specifying the characteristics of the organism are carried in DNA, a large polymer formed from subunits of four kinds (A, G, C, and T). The chemical and structural properties of DNA explain how the genetic information that underlies heredity is both encoded in genes (as a string of molecular "letters") and replicated (by a templating mechanism). Each DNA molecule in a cell forms a single chromosome. [See Content Standard B (grades 9-12)]
  • Changes in DNA (mutations) occur spontaneously at low rates. Some of these changes make no difference to the organism, whereas others can change cells and organisms. Only mutations in germ cells can create the variation that changes an organism's offspring.

BIOLOGICAL EVOLUTION

  • Species evolve over time. Evolution is the consequence of the interactions of (1) the potential for a species to increase its numbers, (2) the genetic variability of offspring due to mutation and recombination of genes, (3) a finite supply of the resources required for life, and (4) the ensuing selection by the environment of those offspring better able to survive and leave offspring. [See Unifying Concepts and Processes]
  • The great diversity of organisms is the result of more than 3.5 billion years of evolution that has filled every available niche with life forms.
  • Natural selection and its evolutionary consequences provide a scientific explanation for the fossil record of ancient life forms, as well as for the striking molecular similarities observed among the diverse species of living organisms.
  • The millions of different species of plants, animals, and microorganisms that live on earth today are related by descent from common ancestors.
  • Biological classifications are based on how organisms are related. Organisms are classified into a hierarchy of groups and subgroups based on similarities which reflect their evolutionary relationships. Species is the most fundamental unit of classification.

Materials:

  • Double-sided Velcro strips in variety of colors – "Velcro One Wrap" packs with multiple colors are available from carft and office supply stores (about $4 a pack) (available on the web at: http://bevfabriccrafts.stores.yahoo.net/velcro15.html). Cut off the ends.

  • Roll of double-sided Black Velcro strips and white Velcro strips

Procedure: 

Cut off the ends of One-Wrap Velcro to create uniform widths of Velcro. In this activity, Velcro strips represent long stretches of DNA.  Each different color represents a different gene or DNA sequence.

         As an advanced option, black Velcro may be used to represent non-coding regions and the white Velcro used to represent regulatory elements.  

1)  Assemble the “chromosome”

Stick together the ends of various colors of Velcro to represent the various genes on a chromosome of DNA. The colorful bits of Velcro represent coding areas.

Optional: You may use white strips of Velcro to represent the control regions of DNA. (In mammals, control regions account for up to 5% of the genome). You may also include large lengths of black Velcro to represent the 95% of the non-coding areas of the human chromosome. (note: bacterial genomes have little non-coding DNA)

2) Simulate a Deletion

Remove a blue Velcro strip from the genome.  This is an example of deletion.  If this gene was important for survival, the cell in which this mutation occurred will not survive. If this mutation was deleterious and in a sperm or an egg cell, the resulting offspring will not survive.

3) Simulate an Insertion

         a) Take the blue Velcro strip you removed and insert it in a new place on the genome. 

         b) Note that sometimes insertions occur in the middle of another gene, which inactivates that gene. One real life example of this is an insertion of a sequence called Alu in the NF-1 gene, thereby causes neurofibromatosis.

4) Simulate a Duplication

Take a red piece of Velcro and imagine that it is copied by bringing in an additional piece of red Velcro.  Move this red DNA to another place on the genome. Some DNA copies itself and inserts a new copy elsewhere on the chromosome. This often happens via transposable elements.

         One important transposable element is the Alu sequence (mentioned above).  Found only in primates, this 300 base pair sequence is repeated about one million times and makes up about 10% of the human genome, accounting for a significant part of the non-coding “dark matter” of the genome.

         Sometimes the copied DNA is recruited to perform a new function.  The DNA may be modified through subsequent point mutations to provide another function in the organism.  An example of this is the lysozyme gene (encoding an enzyme that breaks down cell walls of invanding bacteria) being recruited to serve as the clear crystalin protein in the lens of eye.

5) Simulate Gene Transfer

DNA often moves from one organism to another.  This can happen when we are infected with viruses. Sometimes the virus leaves behind a bit of itself in the host genome.

6) Simulate Interspecies Gene Transfer

Sometimes, DNA move from one species to another.  This is an important source of raw material for evolution.  This has practical implications.  For example, Bird Flu DNA hops from one species of bird to another and eventually into humans. This novel DNA poses a threat to our immune systems.

          In early evolutionary history and for bacterial evolution today, interspecies gene transfer is an important process for creating novelty. (see references to Woese, 2002 and Margulis 2003 below)

  • Viruses
  • Transposable Elements
  • Symbiosis as a source of inherited variation

7) Simulate Recombination

During meiosis, entire stretches of DNA from one chromosome recombine with DNA from another chromosome.

8) Test “irreducible complexity”

In the Intelligent Design movement, “Irreducible Complexity” is a dominant argument why evolution by natural selection can’t explain the diversity of life. According to Michael Behe, author of Darwin’s Black Box, an “irreducibly complex” system is a single system composed of several well-matched, interacting parts that contribute to the base function, where in the removal of any one of the parts causes the system to effectively cease functioning.  His examples of irreducible complexity include the eye, the flagellum, the Krebs Cycle, and other complex cell systems.        

In this exercise, students can take several stretches of DNA from different sources and put them together to create a “complex system”. This simulates how mobile DNA, gene recruitment and natural selection can create complex systems that are not “irreducibly complex.” (see background for more information.)

9) Simulate Fossil Genes

Approximately five percent of the human genome contains genes or regulatory sequences. The remaining 95% of DNA is noncoding. Much of this "Dark" DNA contains "fossil" DNA, that is DNA that was once a useful gene, but because of a mutation, no longer is. Examples of DNA fossils in humans are genes for smell. We share genes with apes that encode smell receptors, but human genes have acquired mutations that render these genes useless.

Additional noncolding DNA includes SINEs (~10% of genome) and LINEs (~20% of genome).

Background Information

How do we account for the genetic variation that underlies the incredible diversity of life? 

Is it possible that random point mutations in DNA produced the diversity and complexity of life?  That is, can the random mutations in single nucleotides account for the vast diversity of form and function we see in life? Most people intuitively feel that the answer is no. Mathematicians confirm this intuition by showing that the probability of this happening is very remote. Indeed, point mutations account for only a part of the genetic diversity that we see today.

The other type of mutation that is so important in evolution is from DNA duplication from mobile DNA.

Variation in DNA is of two types: point mutations and “tinkering,” that is the creation of novel genes by random combinations of preexisting genes.

In evolutionary tinkering, different segments of DNA are like building blocks that get mixed and matched to form all kinds of genetic novelty. Simple changes at the level of DNA can account for big changes in phenotype.

“For instance, despite the 80–100 million years that have elapsed since the human and mouse lineages diverged, the genomes of these two species share 99% homologous genes.  The differences we see in mice and men is not due to creation of new genes, but rather to slight modifications of existing genes.” King Jordan, PNAS

Existing genes provide the raw material for innovation.  Most difference in form is due to a modification of existing genes.  New genes evolve via the duplication, rearrangement and modification of existing genes, rarely through de novo evolution of entire coding sequences.

“It was almost 30 years ago when François Jacob declared that evolutionary innovation (the emergence of novel form and function over time) occurred primarily via a process of "tinkering". By tinkering, Jacob essentially meant the creation of novelty through random combinations of preexisting forms.” ~ King Jordan, PNAS

The probability that billions of nucleotides arose via individual, random point mutations to form a fully functioning suite of proteins is vanishingly small.  The raw material of genetic variation is produced in two ways: by point mutations and by modular mutations, what François Jacob calls molecular tinkering.  This tinkering is analogous to the creation of computer programs.  Once a code for a subroutine has been created, it can be used in millions of different programs to create many different applications.

Mobile Genetic Elements, aka “Jumping Genes”

How do these DNA building blocks move around the genome? Many of them are on mobile DNA.  There are various types of mobile DNA including transposable elements, retrotrasposable elements, plasmids, and the mobile DNA found in viruses.

“Mutations produced by transposons are a source of variation to drive the process of evolution.”

~ Barbara McClintock, discoverer of transposons

Many DNA building blocks are flanked with “transposable elements,” sequences of DNA that allow the duplication and reinsertion of DNA sequences into other parts of the genome.

Transposons, both functional and defunct, make up about 45% of the human genome.

         “One of the largely unanticipated results of mammalian genome sequencing efforts was the revelation of the extent to which these genomes are made up of sequences derived from transposable element insertions. The human genome sequence was found to consist of 45% TE-derived sequences, and this figure is certainly a vast underestimate because many TE derived human sequences have diverged beyond recognition. In addition to being ubiquitous genomic elements, TEs are also autonomous in the sense that they carry the regulatory and protein coding sequences necessary to catalyze their transposition. The ubiquity of TEs, along with the functional machinery that they encode, makes them ideal genetic building blocks that evolution can tinker with to create novel forms.

Examples of Gene Recruitment

         Gene recruitment is the duplication and modification of an existing gene to perform an new function.  Some examples of this include:

  • In the flagellum, the whip-like motor that moves a bacterial cell, many of the proteins involved in this complex are homologous to proteins involved in the Type III Secretory System (TTSS).
  • Lens protein of eye is homologous to lysozyme
  • Leghemoglobin in plants like hemoglobin in animals.

Is irreducible complexity a useful idea?

As we have seen, the probability that billions of nucleotides arose via individual, random, point mutations to form a suite of fully functioning proteins is vanishingly small.  Yet it is this argument that is used to explain “Irreducible Complexity”. Irreducible complexity is the weakly supported idea that complex cellular systems could not have evolved via natural selection and instead require the intervention of an “Intelligent Designer,” some supernatural agent.

In the Intelligent Design movement, Irreducible Complexity is a dominant argument why evolution by natural selection can’t explain the diversity of life. According to Michael Behe, author of Darwin’s Black Box, an irreducibly complex system is a single system composed of several well-matched, interacting parts that contribute to the base function, where in the removal of any one of the parts causes the system to effectively cease functioning.  Some examples of irreducibly complex systems include the eye, the flagellum, the Krebs Cycle, or any number of complex cell systems. The idea of Irreducible Complexity completely ignores evidence of mobile DNA, gene recruitment, jumping genes and DNA tinkering.  The claim of “irreducible complexity” is that individual parts, or genes, of the complex system must be non-functional.  This has repeatedly been shown to not be the case.

Hopefully, this exercise has shown students how tinkering and natural selection can create complex systems that are not “irreducibly complex.”

According to Kenneth Miller, a cell biologist at Brown University, much of what passes as “Irreducible Complexity” could more easily be explained by the argument from “Personal Incredulity.”  This means that if a person cannot conceive of something being true, then it cannot be true. 

A growing number of examples refute the Irreducible Complexity idea.  As more DNA is sequenced and compared, more evidence is found for mobile DNA and gene recruitment in the evolution of complex systems. These and even more examples will refute this weak idea of irreducible complexity.  Because Irreducible Complexity explains nothing in cell evolution, it’s not a useful scientific idea to understand how cells evolved.

References

On the evolution of cells by Carl R.Woese, Proc Natl Acad Sci U S A. 2002 June 25; 99(13): 8742–8747. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12077305

Evolutionary tinkering with transposable elements Jordan, King, PNAS, May 23, 2006, vol. 103, no. 21  pp. 7941–7942 http://www.pnas.org/cgi/content/extract/103/21/7941?etoc

Endless Forms Most Beautiful: The New Science of Evo Devo by Sean B. Carroll. 2005. W.W. Norton, NY.

Acquiring Genomes: A theory of the Origin of Species by Lynn Margulis and Dorian Sagan. 2002. Basic Books. NY.

The Flagellum Unspun: The Collapse of "Irreducible Complexity" by Kenneth Miller

http://www.millerandlevine.com/km/evol/design2/article.html

Mobile Elements: Drivers of Genome Evolution by Haig H. Kazazian, Jr. Science 12 March 2004: Vol. 303. no. 5664, pp. 1626 - 1632

Personal Note and Request for Feedback

In graduate school, my big “ah ha” moment came when I learned about mobile DNA.  The instructor used the term DNA “cassettes” to explain the chunks of DNA that were duplicated and moved around. Suddenly, this one concept of mobile DNA explained so many mysteries of evolution.  Up until then, I only knew about point mutations as the source of variation in DNA.  The huge number of coincident random mutations needed to account for useful changes seemed unbelievably remote. But learning that whole pieces of DNA could be mixed and matched to create new functions made sense.  I eventually did my thesis on gene transfer and gene recruitment in the evolution of novel metabolic pathways.   Mobile DNA explains so much.  I hope that this activity helps provide you and your students with a crucial link in your understanding of how biological evolution works. I am curious to hear how this activity works in your classroom. Please let me know by emailing me at cathus@comcast.net.

 

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