ACTN3

ACTN3: The Gene for Speed

(Photo 3)

(to the left: Photo 3. Depicts the location of ACTN3 on chromosome 11 and the possible genotypes. Genotype frequencies amongst elite athletes is also shown.)

● What chromosome is the gene on? What is the cytogenetic location?
Depicts the location of ACTN3 on chromosome 11 and the possible genotypes. Genotype frequencies amongst elite athletes is also shown.
The ACTN3 is located on the 11th chromosome and its cytogenetic location is 11q13.2.

● How was the gene discovered and located on the chromosome?
The ACTN3 was localized to its chromosome through somatic cell hybrids, a regularly used mapping process, in which viruses are used to fuse cells from two different species together causing the chromosomes to intermingle. However, the human pieces stand out in bands, and when the cells are grown in a line, an array of lines reveals the all the human chromosomes. To locate the gene's location on the chromosome, scientists used fluorescence in situ hybridization.

● What processing has to happen (exons, introns, etc.) in the expression of the gene?
During processing of ACTN3, the mRNA spliceosomes cleave the mRNA strand into 21 distinct introns and 23 distinct exons. The uneven amount is due to two extra exons being attached to the ends of the gene, causing two exons to sit next to each other.

(Photo 2)

● What do we know about about when/where the gene is expressed? (What cell type, body tissue, at what age, etc.)
ACTN3 is primarily located in human skeletal muscle. The next most common place is in the thyroid. This plays into how researchers are studying ACTN3 for its possible application and effect on athletic ability.

● What protein does the gene encode for? What does this protein do? How does it function?
ACTN3 codes for the protein Alpha-actinin-3. The expression of the protein is essentially limited to skeletal muscle, where it is localized to the Z-disc. The protein itself hypothesized to serve multiple roles in different cell types.

(Photo 4)

What form or shape does the protein take?
How does this effect the protein's function?
Actinin filaments are stabilized by the actin binding protein, which is encoded for by ACTN. There are three types of ACTN (types 1-3). Specifically, ACTN3 only encodes for fast twitch muscle.

to the left: Photo 4. Actinin alpha 3

And if you were going to run a PCR lab for ACTN3... what would it look like?

What are the primer logistics for ACTN3?
LEFT PRIMER start: 2976
Seq: c t g a t g a c t t c c g a g c t t g c

RIGHT PRIMER start: 3142
Seq: t t g c t c a g t c g t g t c a g t c t

Product size 167

○ How does the protein act within the cell? How does this affect the body?
Actinin is one of two filaments located in muscle fiber, also known as thin filaments. When muscle fibers contract, the two filaments rub together. ACTN encodes for the protein alpha actinin, which is an actin-binding protein with multiple roles. In skeletal, cardiac, and smooth muscle isoforms they help anchor the myofibrillar actin filaments. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions

● Does the gene affect other genes?
The ACTN3 gene is one of three genes that play a part in the bodies production of actinin. All three genes, though associated with different proteins, are hypothesized to effect each other. However, their exact roles have not been determined by scientists.

(Photo 1)

●       What is the gene’s evolutionary history? Are there related genes in other organisms? How does the gene function in other organisms?
Historically, genes with exercise phenotypes are directly or closely connected to the individual's survival. Since humans are still genetically part of the historic hunter-gatherer that struggle to survive. Homo sapiens adapted to be mobile for long periods of time as they pursued food and game. It was more evolutionarily advantageous to be able to pursue targets for long periods of time, rather than trying to out-sprint their prey. Although humans today do not differ by much from our historic counterparts, studies show that elite endurance athletes share more similarities to our hunter gatherer counterparts. An individual who had an ACTN3 genetic make up similar to those of elite endurance athletes would have a greater chance of survival in a

●       Why would it be beneficial to know about this gene? (Why is it interesting to study this particular gene in the first place?)
Scientists have long searched for the specific genes related to athletic ability. Knowing where exactly in our DNA does are body determine the level of athleticism could be immensely informative. It has become clear that there is not one single gene that codes for a persons entire athletic ability, at the same time research shows that it might not entirely be our genes by themselves. However, ACTN3, is a highly conserved member of the α-actinin family, which are actin binding proteins. Specifically, ACTN3 is a specialized skeletal muscle actin binding protein that is restricted to fast twitch myofibers. These traits are why the gene is now being studied for its potential application to athleticism. The fibers that it effects are responsible for rapid force generation. If researchers are correct, then soon a person could possibly test for what type of athlete they are. What studies say as of now is this: ACTN3 is most likely directly related to athletic ability, but there are also a whole host of other factors that work to effect it.

●       Are there any medical implications of the discovery of this gene? Can it be used to uncover and/or indicate a medical condition? Is there any gene therapy and/or medical treatment for any condition related to this gene?
As stated before, ACTN3 and testing for ACTN3 could possibly be an indicator as to athleticism, but there is not much as to medical implications. The tests that have been done so far are for the presence or lack of ACTN3 and if either of the two have a correlation to ability. Neither situation is detrimental to a person. The only downside or possible condition associated with ACTN3 is that populations with two disrupted copies of the gene displayed slightly lower muscle strength and sprinting ability.

(Photo 5)

Picture above: a graph indicating what proteins ACTN3 codes for and their transcription sites

Sources:

Photo 2: AndrewGNF. "ACTN3 Expression." Wikipedia. N.p., 19 Dec. 2007. Web. 15 May 2014. <http://en.wikipedia.org/wiki/File:PBB_GE_ACTN3_206891_at_tn.png>.

Photo 1: Cassidy, Kyle. "Running Man." Wikipedia. N.p., Jan. 2013. Web. 15 May 2014. <http://simple.wikipedia.org/wiki/File:Running_Man_Kyle_Cassidy.jpg>.

Photo 4: Emw. "Protein ACTN3." Wikipedia. N.p., 15 Dec. 2009. Web. 15 May 2014. <http://en.wikipedia.org/wiki/File:Protein_ACTN3_PDB_1tjt.png>.

Photo 3: Macur, Juliete. "Born to Run? Little Ones Get Test for Sports Gene." New York Times. nytimes, 19 Nov. 208. Web. 15 May 2014. <http://www.nytimes.com/2008/11/30/sports/30genetics.html?pagewanted=all&_r=1&>.

Photo 5: NCBI. National Center for Biotechnology Information, 13 May 2014. Web. 15 May 2014. <http://www.ncbi.nlm.nih.gov/gene/89>.

Banner photo: "People Man Runner Silhouette Person Cartoon." Pixabay. Pixabay, 13 Apr. 2012. Web. 15 May 2014. <http://pixabay.com/en/people-man-runner-silhouette-33482/>.

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http://kohlmanngen677s13.weebly.com/

http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=36a&c=Gene&l=ACTN3

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