Tag Archives: ancient gene

Day 2 (1p36.23-1p36.13): mTOR, a gateway to cell growth


Day 2 has 125 protein-coding genes, including the gene encoding mTOR (the mechanistic target of rapamycin). mTOR commemorates two places in its name. Rapamycin, an antifungal drug that is also used to prevent transplant rejection, was named after Rapa Nui (Easter Island) where it was discovered. And according to Joseph Heitman, who worked to discover the TOR genes in yeast:

TOR also means door or gateway in German, and the TOR protein serves as a gateway to cell growth and proliferation. This name also commemorates the city in which TOR was discovered, as Basel is an older European city once ringed by a protective wall with large decorative gates, including one still standing, named the Spalentor.

"Basel - Spalentor" by Taxiarchos228 - Own work. Licensed under FAL via Commons - https://commons.wikimedia.org/wiki/File:Basel_-_Spalentor.jpg#/media/File:Basel_-_Spalentor.jpg

“Basel – Spalentor” by Taxiarchos228 – Own work. Licensed under FAL via Commons – https://commons.wikimedia.org/wiki/File:Basel_-_Spalentor.jpg#/media/File:Basel_-_Spalentor.jpg

mTOR is a kinase that regulates cell growth and is important in many diseases. Mutations that activate mTOR can lead to cancer. Therefore it is an attractive drug target.

The mTOR gene is truly ancient – it can be found in species as distant as rice. This suggests that it is as old as the common ancestor of eukaryotes (> 1.6 billion years).

Click here to jump to the location of a S2215F mutation in mTOR (flashing) which has been found in multiple skin cancers. Note that the mutation isn’t a SNP in the reference sequence – it’s listed as just the reference (A). That is because S2215F is found in tumors but not in normal genomes – it is a somatic mutation that happens in a subset of cells during cancer, but has never been observed as an inherited mutation.

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Day 5 (1p34.3-1p34.2): Argonaute

“Argonauta argo Merculiano” by Comingio Merculiano (1845–1915) in Jatta Giuseppe – I Cefalopodi viventi nel Golfo di Napoli (sistematica) : monografia. Licensed under Public Domain via Commons – https://commons.wikimedia.org/wiki/File:Argonauta_argo_Merculiano.jpg#/media/File:Argonauta_argo_Merculiano.jpg

Day 5 has 108 protein-coding genes, including AGO1 (argonaute 1 RISC catalytic component.) Argonaute is an critical part of the cell’s RNA interference (RNAi) machinery.

Fire and Mello won the 2006 Nobel Prize in Physiology or Medicine for their characterization of RNAi using the nematode C. elegans in 1998, but the gene Argonaute got its name from a group working in the plant A. thaliana. They named the gene family Argonaute because mutations in the plant’s version of the genes led to an appearance that reminded them of a small squid, and named it after the octopus Argonauta argo.

Argonaute proteins are ancient: even bacteria have a version of them, which they use to chew up foreign DNA as a defense against viruses.

Click here to see your human version of AGO1.

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Day 6 (1p34.2-1p32.3): MUTYH, a DNA repairer



Day 6 contains 99 protein-coding genes, including MUTYH (mutY homolog). Throughout life, your cells suffer DNA damage, which is constantly repaired by enzymes – one of which is made by the gene MUTYH.

When the DNA encoding a repairer like MUTYH is itself mutated, though, mutations can start to run amok in the genome, leading to cancer. Inherited MUTYH variants are associated with polyposis and colon cancer.

MUTYH is named after the mutY gene in E. coli bacteria. The similarity to a bacterial gene means that it is as ancient as the common ancestor of prokaryotes and eukaryotes (>1.7 billion years.)

Click here to see your MUTYH gene where you will see a cancer-associated variant flashing.

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Day 9 (1p31.2 – 1p31.1): ACADM, an enzyme that breaks down fatty acids

“Acyl CoA dehydrogenase active site” by Ecthompson2009 at English Wikipedia (original Author:Elizabeth Thompson and Megan Carmony) – http://en.wikipedia.org/wiki/File:Acyl_CoA_dehydrogenase_active_site.jpg. Licensed under CC BY-SA 3.0

Day 9 contains 27 protein-coding genes – a very gene-sparse region. So it is predictable that the most-cited gene in this region is more arcane than the stars of other regions. It is ACADM (acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain), encoding an enzyme that breaks down medium-chain fatty acids. Problems with this gene can cause a rare metabolic disease.

ACADM is billions of years old, because it is found in both bacteria and humans. Sequence analysis suggests that we didn’t inherit our ACADM directly from bacteria, but they were in the bacteria that eukaryotes engulfed that became mitochondria (endosymbiosis.) Even though the ACADM gene is now in the nuclear genome, the protein still does its work in the mitochondria!

Click here to see rs77931234, the most common mutation in ACADM causing MCAD deficiency. The frequency of this mutation is about 0.5% on European chromosomes.

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