Welcome Guest [Log In] [Register]


Welcome to Rabbit Addict.

The forums are a place to discuss all things related to rabbits and cavy. From breeding to pet, emergency to genetics questions. Our members are a mix of genetics enthusiasts, breeders, and pet owners looking to share their animals.

Hop on in and join the fun!
We don't bite. I promise.



You're currently viewing our forum as a guest. This means you are limited to certain areas of the board and there are some features you can't use. If you join our community, you'll be able to access member-only sections, and use many member-only features such as joining the discussion, customizing your profile, sending personal messages, and voting in polls. Registration is simple, fast, and completely free.

If you're already a member please log in to your account to access all of our features:

Username:   Password:
Add Reply
agouti gene - learned something new!
Topic Started: Jan 18 2013, 12:07 PM (1,262 Views)
NeuBunny
Genetics Geek!
[ *  *  *  *  *  *  *  * ]
so, after ages of looking, I finally found some good sources on color genetics for goats. And learned something new about rabbit and cavy genetics in the process. Just thought I would share.

Think the A gene on rabbits is confusing with 3 alleles (agouti, tan and self) in a simple dominance series? I struggled with why they 'acted different' in guinea pigs (which have 4 alleles - agouti, solid, tan and self) - where tan is co-dominant with agouti and solid even though agouti is dominant over solid.

Goats have at least 14 A-gene alleles!! All are considered co-dominant, but the rule is actually very simple. If one gene of the pair says to make a part eumelanin (e.g., black) and the other gene says to make it phaeomelanin (e.g., tan) - phaeomelanin always wins! This rule actually works for all 3 species!!!

In rabbits, agouti has the tan color (phaeomelanin) in the midband, eye circles, triangle and tummy. That's the most of any of the three. In the tan rabbit, the tan color is just in the eye circles, triangle and tummy. The tan rabbit doesn't have tan anywhere that the agouti is black - so when you have both genes (Aat), all the tan of the agouti shows and none of the black gets messed up. It 'acts' like simple dominance. That's different than in the cavies. A tan cavy has tan color in some places (e.g., pea spots, eye circles, side ticking) that the agouti cavy doesn't. So Aat in the cavy 'messes up' and changes to tan some of the coat parts that should still have black ticking if A were really dominant -- most notably Aat look like agoutis, but have pea spots that lack ticking. The weirder one is the solid (Ar) - which should have black ticking on its tummy (same as the rest of its body). But Arat cavies look mostly like agoutis -- with the same all-tan belly band (and pea spots too). Makes sense by the 'goat rule' in that the tan cavies have solid tan tummies without ticking (all phaeomelanin) and 'phaeomelanin always wins'.

Now if I can just figure out the E-gene. All three species have E-genes which also mess with the phaeomelanin-eumelanin balance. But I think they must be very different alleles in each species. The only consistent pattern I can see is that they all 'override' the A-gene instructions (though torts and reds are clearly different, so A is still important in rabbits even when they are ee), and in general the more dominant genes (think steel in rabbits) push towards more eumelanin (more black) while the more recessive (tort and red in rabbits) toward more phaeomelanin.

Anyway, I thought it was really cool, but all my real world friends and family just look at me like I'm crazy -- so I thought I would share here!
Offline Profile Quote Post Goto Top
 
redbunny
Member Avatar
Hey, look at you! You chatterbox you. Now you can request a new title! PM the Admin to do so
[ *  *  *  *  *  *  *  * ]
Most interesting post I've seen for ages. Thank you.
Offline Profile Quote Post Goto Top
 
sidd-says-gimme
Member Avatar
sidd says stay gold
[ *  *  *  *  *  *  *  * ]
Very interesting - will have to read a few more times to fully get it though. :giggle:

Thanks for sharing.
Offline Profile Quote Post Goto Top
 
redbunny
Member Avatar
Hey, look at you! You chatterbox you. Now you can request a new title! PM the Admin to do so
[ *  *  *  *  *  *  *  * ]
This was the reason for joining the forum as I've kinda read everything easily found on line in Google searches. Love genetics and rabbit colours. I have some interesting colours in my ND including red, silver and the hotots which I'm dealing from scratch because unlike the States(which has the key incredible examples) the uk is very short on them.
Offline Profile Quote Post Goto Top
 
reh
Member Avatar
Get the Duct Tape, Stat!
[ *  *  *  *  * ]
This is very consistent with / exactly describes the function of the A and E genes.

The agouti gene temporarily produces ASP (Agouti signal protein), which signals the pigment cells to produce yellow/red pheomelanin. Without ASP the cells make black (or brown) pigment.
ASP may be expressed differently on belly / back. For proper ASP production one allele is sufficient.
Dominant mutations = more yellow/red, recessive ones = more black/brown

The extension gene produced a cell receptor (MC1R). If the ubiquitous MSH binds to it, the receptor becomes activated and the cell produces black/brown eumelanin.
If ASP binds to this receptor, it becomes inactivated, the cell makes ...
... right, pheomelanin.

Mutations leading to a permanently active / over active receptor are dominant (dominant black, steel).
Mutations leading to a partly or entirely broken receptor by hindering/inhibiting signaling are recessive.

In rabbits ee isnt a broken receptor, but a partly nonfunctioning one, so ASP can act something.
Japanese is a dominant receptor (black parts) which is not produced in yellow parts (therefore on homocygout eJeJ rabbits there is no black pigment in its yellow hairs, no matter if the rabbit is A or a.

Dominant mutations = more black/brown, recessive ones = more yellow/red
Dominant yellow (f.e. in mice) = always available ASP, recessive yellow = broken MC1R receptor.
Dominant black = overactive MC1R, recessive black = nonexisting ASP.

further explanation here: http://s4.zetaboards.com/Rabbit_Addict/single/?p=9052444&t=9867798
www.rabbitcolors.info - Images and Gene Codes
www.satinangora.de
Offline Profile Quote Post Goto Top
 
NeuBunny
Genetics Geek!
[ *  *  *  *  *  *  *  * ]
reh -- I feel like other people probably do reading my posts -- like I know all the words, but still can't quite see the picture. It's been a while, but I was a chem minor (and took a lot of biochem in grad school), so I also feel like I should :bonk: be able to understand.

Let me know if I have this right putting it in my own words...

At any point in time, the cell makes only eumelanin OR phaeomelanin, never both at once. (that is, it's not a case where both pigments are present but we only see one).

The A-genes produce a protein (ASP) which sends the instruction 'make phaeomelanin' (instead of, not in addition to, eumelanin). Depending on WHICH A-allele it sends the instructions to 'make phaeomelanin' to particular cells (producing pattern) at particular times in hair growth (banding).

The dominant agouti allele (A) sends the instructions to make ASP (= make phaeomelanin) in the belly, eye circles and midband. When and where ASP isn't turned on, the 'pigment factory' sill makes eumelanin.
The intermediate tan allele (at) sends the instructions to make ASP (= make phaeomelanin) in the belly and eye circles.
The recessive self allele (a) does NOT send instructions to make ASP (= no phaeomelanin made) = still all eumelanin.

[with more options for patterns in cavies and goats, but the same chemistry]

If one allele of the gene pair is NOT making ASP (e.g., a) while the other allele IS making ASP - there is still enough ASP to switch all the eumelanin production to phaeomelanin (you still don't get both proteins, just the phaeomelanin).

Is eumelanin actually a 'precursor' to phaeomelanin -- that is, is the cell making eumelanin and then the ASP converting it to phaeomelanin in a two-step process? Or is it more like one set of 'machinery' that can only make one pigment or the other? I had been thinking the former, but your description makes it sound more like the latter.


I'm picturing this in my head as a little pigment-making factory with a keyhole (MC1R). ASP is only one of two protein keys that can fit into the keyhole. The other is MSH. Normally, the factory is set to make phaeomelanin. But there is LOTS of MSH in the cell, so usually, the MSH floats in and acts as the key to switch the factory over to make eumelanin. When ASP is present, it binds to the keyhole so the MSH won't fit -- then the switch stays in the phaeomelanin position. The Agouti form (A) of ASP must breakdown periodically in some cells, resulting in periods where MSH can sneak in and turn the key to eumelanin creating bands.

Normal extension (E) then codes for the correct keyhole AND the initial position of that switch at phaeomelanin.

The 'dominant black' ED alleles (dominant black of angora goats, for example which gives an all black coat) then are a 'broken keyhole' that ASP won't fit into but MSH does. MSH can still 'turn the switch' to make eumelanin, but ASP can't block it. So long as you have even one of these dominant black alleles (e.g., EDE genotype) you have a factory with a 'working switch' and have eumelanin produced.

Question -- in this case (EDE genotype), is the cell actually making both proteins (but you only see the darker eumelanin) or is the cell making only eumelanin?

The 'recessive red' E alleles (e of cavies and Er of goats, both of which produce an all red coat) then is a modification to the MC1R keyhole which makes it so that MSH doesn't fit. The switch can never be turned to eumelanin and only phaeomelanin is produced. It makes sense that this would be a true recessive - so long as the other gene of the pair is making the 'correct' keyhole, MSH can still get in and turn the switch to make eumelanin.

I can see steel as 'overactive' where maybe something is off and the MSH 'sticks' in the receptor once it gets there. ASP still 'gets in' to make the first band, but after the first shift to eumelanin the ASP can't get back in. Do steel rabbits still have tan bellies? But it isn't just a timeline phenomenon because following a molt the new hairs each get a phaeomelanin tip again.

I'm not sure I follow at all why the recessive e of rabbits works so differently in combination with the various A-alleles. I do see how a receptor could be partially functioning, but it seems to be imposing its own pattern which doesn't seem particularly related to the underlying A-pattern at all. In combination with the aa alleles (no ASP) it LOOKS like a temperature sensitive gene, such that in the warmest parts of the body MSH no longer fits the switch and eumelanin production fails to turn on and the switch stays in the phaeomelanin position. In combination with an agouti A allele (ASP) it looks like ASP still blocks the keyhole so all the parts of the coat that are normally phaeomelanin stay phaeomelanin. MSH no longer fits the switch anywhere (not temperature sensitive), but instead of the normally-eumelanin portions of the coat staying as phaeomelanin, pigment production in those parts fails altogether leaving eye circles, belly, and undercoat white.

Harlequin (ej) is even more interesting because it acts differently in the rabbits and cavies (though perhaps it isn't really the same allele).

In cavies, you can still see the A-genes in the 'eumelanin' patches (which can have the phaeomelanin agouti banding). The patching indicates that the gene turns on/off (but not randomly) at some stage during embryogenesis (I'm thinking to get the ideal pattern it should be making that 'decision' at about the 8-32 cell stage). In cavies the ej allele is basically is a 'recessive red' gene that fails to activate in some patches.

In rabbits, it seems patches are either eumelanin or phaeomelanin, regardless of the A gene (though some people have told me that the bellies of agouti-based harlequins are solid phaeomelanin, while in self-based the patching extends over the belly - I can't find this documented). Thus for rabbits it seems like the switch gets permanently stuck at either eumelanin or phaeomelanin (even with agouti alleles to produce ASP, there is no phaeomelanin in the eumelanin patches). You suggest that in the patches where it is 'turned on' it acts as a dominant black - ASP doesn't fit the receptor and so eumelanin is produced. But in the portions of the coat where it is 'off' it doesn't show the normal pattern either -- in the 'red patches' it acts as a recessive red where MSH can't turn on eumelanin. Very strange little gene.



Offline Profile Quote Post Goto Top
 
reh
Member Avatar
Get the Duct Tape, Stat!
[ *  *  *  *  * ]
Pigment factory is good, its the title of my german writing about this whole thing :-)

The receptor sits in the cell membran, the "keys" are outside of the cell (so cells can react to external substances unable to enter the cell).

The first part of melanin synthesis is the same for both colors, then it splits in different ways. The pheomelanin needs sulfur containing elements like cystein. Even black melanosomes contains pheomelanin. It is produced first as long as cystein is available. After its run out, eumelanin is produced, so eumelanosomes have a core of pheomelanin, overlaid with eumelanin.

Pigment type switching causes a bunch of genes switched of, f.e. the brown gene and the pink eyed dilution gene (probably lutino) dont work in yellow producing cells.
The origin of ASIP is the hair papilla.

I explained the subject on a info poster on the Europe show:
Quote:
 
To create the alternating colored bands on Agouti hairs, the pigment cells need to switch between the production of black and yellow pigments during the growth of the hair. This change is called pigment type switching. It is also responsible for the creation of areas with just light or just dark colored hairs.
The process is similar to that of a key lock, for example the ignition lock in a car. The receptor MC1R being the lock, the melanocyte-stimulating hormon MSH and the agouti signal protein ASIP being keys. MSH is always present, whilst ASIP only becomes available during the growth of the yellow portion of the hair.
MSH causes the switch to signal. The signal induces the pigment-creating cells to produce black pigment. The key ASIP admittedly fits into the switch, but doesn't switch on the signal and therefore prevents the use of the MSH-key.
A cell with working switch therefore produces black pigment in the presence of MSH. If ASIP becomes available temporarily, it replaces the MSH and turns off the signal. Thus the cells produces yellow pigment.
The Extension series holds the construction plan for the key switch, the Agouti series the
construction plan for the ASIP. MSH-Mutations can create switches which are either constantly active / overactive (steel) or are defect (yellow). For ASIP a fault in the construction plan may interrupt the key production leading to nonfunctioning keys.
A special case is the Japanese factor. It resembles the gene for steel/dominant black, yet it only acts in the dark areas of the coat. It is not active in the light parts, so there are no switches at all.
Therefore the Japanese factor is actually recessive towards the nonextension gene in the light areas, whilst it is dominant towards the normal extension in the dark areas.

Agouti hairs (even steel) have always dark tips and a single middle band. The yellow is on the most thick part of the hair (called granne in german).
Steel hairs have a narrow band on the guard hairs ("first" band), but no or nearly no band on wool hairs ("second" band).

Not the keyhole is broken but the switch itself dont react properly.

Yes, tort rabbits look like they are temperature sensitive and actually they ARE!
Posted Image Posted Image
A scientist working with this things commented about the type of mutation occuring in e of rabbits, it very good could be that this causes a structual instability which may be stabilized by cold. But nobody ever investigated how this works, there are only the experiments of Schultz, who found the cold sensibility of himis.

If you have a scientific library near you look for this:
Lamoreux, M, Véronique Delmas, und Dorothy Bennett. 2010. The Colors of Mice: A Model Genetic Network. Wiley-Blackwell. http://onlinelibrary.wiley.com/book/10.1002/9781444319651 (Part 1 is readable online, contains a graphic about melanogenese)

For more general function of g protein coupled receptors one of the thick "Biology" books bay be sufficient)

This is free to read:
Slominski, Andrzej, Desmond J. Tobin, Shigeki Shibahara, und Jacobo Wortsman. 2004. „Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation“. Physiol. Rev. 84 (4) (Oktober): 1155–1228. http://physrev.physiology.org/cgi/content/abstract/84/4/1155

Edited by reh, Jan 28 2014, 06:03 AM.
www.rabbitcolors.info - Images and Gene Codes
www.satinangora.de
Offline Profile Quote Post Goto Top
 
NeuBunny
Genetics Geek!
[ *  *  *  *  *  *  *  * ]
thanks!
Offline Profile Quote Post Goto Top
 
NeuBunny
Genetics Geek!
[ *  *  *  *  *  *  *  * ]
In case anyone is interested, I got my goat genetics pages posted...

http://minifluffsrabbitry.weebly.com/moms-genetics-pages.html
Offline Profile Quote Post Goto Top
 
redbunny
Member Avatar
Hey, look at you! You chatterbox you. Now you can request a new title! PM the Admin to do so
[ *  *  *  *  *  *  *  * ]
Dear REH! I've enjoyed the degree of sophistication in your posts. I'm a cell biologist with a huge interest in genetics and have found your comments intriguing and enlightening. Thank you.
Offline Profile Quote Post Goto Top
 
reh
Member Avatar
Get the Duct Tape, Stat!
[ *  *  *  *  * ]
Thanks :-)
Have we had email contact before?
I like to know more about how it all works on a cellular level, but it seems nobody knows :-(
www.rabbitcolors.info - Images and Gene Codes
www.satinangora.de
Offline Profile Quote Post Goto Top
 
redbunny
Member Avatar
Hey, look at you! You chatterbox you. Now you can request a new title! PM the Admin to do so
[ *  *  *  *  *  *  *  * ]
No email contact but that can change! I was wondering where all the academics publish their research. I know when I was at college there was mountains of work done on rabbit coat colour genetics.
Offline Profile Quote Post Goto Top
 
redbunny
Member Avatar
Hey, look at you! You chatterbox you. Now you can request a new title! PM the Admin to do so
[ *  *  *  *  *  *  *  * ]
Oh my goodness...... Reh I have just seen your website.....is that coat colour site really yours? Und...... Deutschland! How wonderful. I'm just outside London but my parents are from Duisburg.
Offline Profile Quote Post Goto Top
 
reh
Member Avatar
Get the Duct Tape, Stat!
[ *  *  *  *  * ]
yes ;-)
There could be more rabbits, but very few people really contribute entries :-(
So, if someone have an interesting colored rabbit or one where only few entries exist for, please add your rabbits (i can help with the gene code).

Quote:
 
I was wondering where all the academics publish their research. I know when I was at college there was mountains of work done on rabbit coat colour genetics.
Try "Fontanesi rabbit". There are not much current investigations about rabbit colors beside this. It helps to look for general information about melanocytes, pigmentation, ... on other animals (mice!).
You can search for scientific publications on Scirus, Pubmed, google scholar, ...

There are lots of old papers, much of them scanned and online available, from Castle, Sawin, ..., the old school geneticists.

Maybe i should think about a way to put my collected citations/references online.

Do you speak german?


Edited by reh, Feb 3 2013, 06:23 PM.
www.rabbitcolors.info - Images and Gene Codes
www.satinangora.de
Offline Profile Quote Post Goto Top
 
redbunny
Member Avatar
Hey, look at you! You chatterbox you. Now you can request a new title! PM the Admin to do so
[ *  *  *  *  *  *  *  * ]
Dear reh despite my siblings being fluent German speakers I never managed it......but I found science very easy and that's the path I took. Combining that with the rabbits brought me here!

I am delighted with all of your incredible suggestions re genetics etc. Ich danke ihnen sehr.
Offline Profile Quote Post Goto Top
 
1 user reading this topic (1 Guest and 0 Anonymous)
ZetaBoards - Free Forum Hosting
Create a free forum in seconds.
Go to Next Page
« Previous Topic · Genetics and Colors · Next Topic »
Add Reply