Day 10 (1p31.1-1p22.3): CYR61, a protein secreted at wounds

https://upload.wikimedia.org/wikipedia/commons/c/c0/BandAid.jpg

Day 10 has 32 protein-coding genes. One is CYR61 (cysteine-rich angiogenic inducer 61), when encodes a protein that is secreted from cells into the extracellular matrix in response to wounds, tumors, and other sites of inflammation.

CYR61 is notable because the proteins we have seen so far have lived inside or on the surface of the cell. When a cell makes a protein like CYR61, how does it know to secrete it, while keeping others in the cell? The answer is in a sequence of amino acids at the beginning of the protein known as the signal peptide. Gunter Blöbel won the 1999 Nobel Prize for Physiology or Medicine for discovering signal peptides. The UniProt database highlights this sequence at the beginning of the CYR61 protein. Note that the amino acid sequence of the protein, unlike the 4-letter alphabet of DNA, is conveyed using a 20-letter alphabet.

CYR61 is found across bony vertebrates, meaning it originated over 420 million years ago.

Click here to see your CYR61 gene.

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Day 11 (1p22.3-1p21.3): BRDT: a male contraceptive target named for a god

"Brahma Musée Guimet 1197 1" by Vassil - Own work. Licensed under Public Domain via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:Brahma_Mus%C3%A9e_Guimet_1197_1.jpg#/media/File:Brahma_Mus%C3%A9e_Guimet_1197_1.jpg

“Brahma Musée Guimet 1197 1” by Vassil – Own work. Licensed under Public Domain via Wikimedia Commons – https://commons.wikimedia.org/wiki/File:Brahma_Mus%C3%A9e_Guimet_1197_1.jpg#/media/File:Brahma_Mus%C3%A9e_Guimet_1197_1.jpg

Day 11 has 54 protein-coding genes, including one named after a god: BRDT (bromodomain, testis-specific.) Bromodomain proteins are special because they can recognize a chemical modification of proteins (acetylation of lysines) that is often used in gene regulation. Enzymes with bromodomains can use them to turn genes on and off by taking acetyl groups on and off of the tails of the histone proteins that the genome is wrapped and packed around.

The bromodomain is not named after the element bromine, but rather after the brahma gene of the fly Drosophila melanogaster, where it was discovered as a gene regulator in 1988. Other regulators discovered in the same genetic screen were also named after deciders of fate, such as urdursallimus, and moira

Because BRDT is only expressed in sperm, it has been considered an attractive male contraceptive target.

The bromodomain is conserved in organisms as distant as yeast, meaning it is at least a billion years old.

Click here to see your BRDT gene, and here to see its bromodomain (highlighted.)

 

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Day 12 (1p21.3-1p21.1): Tissue factor, a protein that senses bleeding

Clotting of human blood plasma after addition of thromboplastin. A gel-like structure is formed that is strong enough to hold a steel ball. By Dietzel65, Steffen Dietzel (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

Day 12 has 32 protein-coding genes including F3, also known as coagulation factor III, thromboplastin, or tissue factor. F3 protein is expressed on the surface of cells that ordinarily should not be exposed to blood. When bleeding occurs and F3 is exposed to the blood, a series of clotting reactions is activated.

F3 is found throughout bony vertebrates, so it is at least 440 million years old.

Click here to see your F3 gene.

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Day 13 (1p21.1-1p13.2): two Shaker channel genes, the targets of scorpion venom

"Deathstalker ST 07" by by Ester Inbar, available from http://commons.wikimedia.org/wiki/User:ST.. Licensed under Attribution via Commons - https://commons.wikimedia.org/wiki/File:Deathstalker_ST_07.JPG#/media/File:Deathstalker_ST_07.JPG

“Deathstalker ST 07” by by Ester Inbar, available from http://commons.wikimedia.org/wiki/User:ST.. Licensed under Attribution via Commons – https://commons.wikimedia.org/wiki/File:Deathstalker_ST_07.JPG#/media/File:Deathstalker_ST_07.JPG

Day 13 has 76 protein-coding genes, including KCNA2 (Kv1.2) and KCNA10 (Kv1.8), encoding two Shaker-type potassium channels used by nerve cells. The name “shaker” comes from the fly Drosophila melanogaster, where the gene was first discovered. Mutations cause the flies’ legs to shake, even when anesthetized.

Shaker-type potassium channels are the target of agitotoxin, a component of the deathstalker scorpion‘s venom.

Go to Day 13 to see rs786205231, a mutation in KCNA2 that has been associated with early onset epilepsy. Note that KCNA2 is an unusual single-exon gene.

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Day 14 (1p13.2-1p12): PTPN22, tuning the immune response

https://commons.wikimedia.org/wiki/File%3AHealthy_Human_T_Cell.jpg

https://commons.wikimedia.org/wiki/File%3AHealthy_Human_T_Cell.jpg

Day 14 has 67 protein-coding genes, including PTPN22 (Protein tyrosine phosphatase, non-receptor type 22 lymphoid). The PTPN22 protein is expressed in cells of the immune system, and is one small part of the complicated signaling cascades that they use to coordinate their activity.

PTPN22 is a particularly interesting gene because variation in the gene is associated with many autoimmune disorders like rheumatoid arthritis, Crohn’s disease, lupus, and vitiligo. One variant, rs2476601 (R620W) is present in about 20% of people with European ancestry, and increases the risk of autoimmune diseases by about twofold. Why wouldn’t evolution rid the population of this mutation? It may confer some benefit by strengthening the immune response to infection, at the same time it increases the chance the immune system will attack the body.

The PTPN22 gene is shared across four-legged vertebrates, meaning it is at least 360 million years old.

Click here to see the rs2476601 mutation in PTPN22 (flashing).

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Day 15 (1p12-1q12): The centromere of Chromosome 1

https://commons.wikimedia.org/wiki/File:Condensed_Eukaryotic_Chromosome.png

https://commons.wikimedia.org/wiki/File:Condensed_Eukaryotic_Chromosome.png

On Day 15 there are only 7 protein-coding genes, and then we hit the centromere of Chromosome 1 – the place where the two sister chromatids meet, the middle of the classic “X” shape of microscope pictures of metaphase chromosomes. The centromere is where sister chromatids are grabbed by the cell during cell division.

You’ll notice that the sequence at the centromere is mostly displayed lowercase – made up of long noncoding sequences called satellite DNA, repeated over and over. This sequence at the centromeres may not actually be used by the cell to locate the centromere. It has been proposed that the location of the centromere is remembered epigenetically when the cell divides, and across generations.

The centromere is also where we switch over from the short (p) arm to the long (q) arm.

Click here to see the centromere of Chromosome 1.

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Day 16 (1q12): No man’s land

 

Day 16 is entirely “N” – no sequence is available. This is one of the vastest expanses of constitutive heterochromatin in the genome – a region that is always turned off and tightly packed. Like the centromere, the sequence is likely many copies of satellite DNA.

If you’d like to see the letter N repeated 8,584,704 times, click here for Day 16.

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Day 17 (1q12-1q21.1): RBM8A – the cell’s memory of the splicing process

 

https://commons.wikimedia.org/wiki/File:X-ray_of_arm_showing_absent_radius_and_radially_deviated_hand,_caused_by_Thrombocytopenia_and_Absent_Radius_syndrome.jpg

https://commons.wikimedia.org/wiki/File:X-ray_of_arm_showing_absent_radius_and_radially_deviated_hand,_caused_by_Thrombocytopenia_and_Absent_Radius_syndrome.jpg

Day 17 starts with the constitutive heterochromatin of Day 16, then continues with 23 protein-coding genes, including RBM8A (RNA-binding protein 8A). RBM8A encodes an RNA-binding protein. RNA-binding proteins can regulate the expression of genes by influencing the rate that messenger RNAs made from genes are degraded and translated into proteins.

RBM8A protein plays a role in the fascinating process of nonsense-mediated decay: cells detect mRNAs with premature stop codons (due to mutatations or mistakes in splicing) and destroy the transcript because making a partial protein could be more toxic than no protein at all.

The cell detects premature stop codons by seeing if there was an intron after the stop codon. In order to know this, it has to have a memory of splicing events while the ribosome is translating the mRNA. That memory is provided by the exon junction complex, which is stuck to the mRNA like a Post-It Note where splicing happened. RBM8A is part of that complex.

Deletion of the RBM8A causes TAR syndrome which leads to the absence of the radius bone in the forearm.

The nonsense-mediated decay system is ancient – conserved across all domains of life, so it is billions of years old.

Click here to see Day 17, jumping to RBM8A.

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Day 18 (1q21.1-1q21.3): The epidermal differentiation cluster: a bunch of genes that build your skin

https://commons.wikimedia.org/wiki/File:Normal_Epidermis_and_Dermis_with_Intradermal_Nevus_10x.JPG

Day 18 has 192 protein-coding genes. Over 50 of them encode proteins that build the epidermis, or the outer layer of the skin. This cluster of genes is called the epidermal differentiation cluster. Your skin is constantly being replaced by new cells that migrate from lower layers of the skin into the epidermis. Over the course of four to six weeks, they turn on these differentiation genes to secrete waterproof and flexible proteins into the epidermis, and undergo a kind of programmed death called cornification.

This cluster of genes is conserved in the same order (synteny) across mammals and reptiles. Their evolution was an important step in adapting to life out of the oceans.

Click here to see the LOR (loricrin) gene and Day 18. Note that almost half of the amino acids are glycine (colored gray), which is important to forming waterproof bonds between proteins.

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Day 19 (1q21.3-1q23.3): The Duffy receptor, rapidly evolving against malaria

https://commons.wikimedia.org/wiki/File:%22Don%27t_Strip-tease_for_Anopheles%22_-_NARA_-_514166.jpg

Day 19 has 209 protein-coding genes, more than any other day of Chromosome 1. On this very gene-dense day is the gene ACKR1 (atypical chemokine receptor 1) which encodes the famous Duffy chemokine receptor.

Like A/B/O blood types and the Rhesus antigen, the Duffy receptor is the basis of a blood type, where different people have different versions of the protein on blood cells. The Duffy receptor is the entry point for malaria into blood cells.

ACKR1 is one of the few places in the genome where there are strong differences between ethnic groups. An inactivating mutation is found in almost all people of West African descent and almost no people of European descent. Strong geographic differences like these are almost always due to natural selection, and the ACKR1 inactivation is thought to confer protection against malaria where it is endemic.

Click here to see the Fyb- mutation, which will be flashing. Note that it is before the protein-coding part of the gene. It disrupts the binding site for a transcription factor needed to turn the gene on in blood cells.

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