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How dominance works at the DNA/RNA/protein

Genetics as it applies to evolution, molecular biology, and medical aspects.

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How dominance works at the DNA/RNA/protein

Postby mhwombat » Wed Oct 03, 2012 5:57 pm

I'm having difficulty figuring out how dominance happens at the DNA/RNA/protein level. Here is what I think I know, and the questions that I have. If someone can correct my mistakes and fill in the gaps, or direct me to a good resource, I'd be grateful. All I need is a high-level mental model of how it works. Suppose we are interested in a particular gene, one that is not sex-linked, and we're ignoring complications like epigenetics.

Each chromosome has two strands of DNA, one from the father and one from the mother. Somewhere on one of the chromosomes is a DNA segment that codes for our gene. A segment on one strand codes for one allele, and the corresponding segment on the other strand codes for the other allele. The two alleles may or may not be identical.

The first step of gene expression is transcription, which operates on a single strand of DNA to produce a single strand of RNA. So are both strands of the chromosome transcribed, yielding two strands of RNA? Is our gene now represented as corresponding segments of the two RNA strands, so we still have the two alleles, each of which is represented as a sequence of codons? Or does the dominance relationship "take effect" at this point?

The next step is translation, which operates on a single strand of RNA to produce proteins. So are both strands of RNA translated, yielding two sequences of proteins? Is our gene now represented as two corresponding segments of the two protein sequences? Or does the dominance relationship "take effect" at this point, so that in theory we could examine the proteins and somehow "read" which allele was expressed?
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Re: How dominance works at the DNA/RNA/protein

Postby JackBean » Thu Oct 04, 2012 11:58 am

mhwombat wrote:Each chromosome has two strands of DNA, one from the father and one from the mother.

No

mhwombat wrote:A segment on one strand codes for one allele, and the corresponding segment on the other strand codes for the other allele.

No

The dominance can be of effect at any stage. Because of faulty promotor, the gene may not be transcribed. There may be something wrong with the mRNA (missing splicing points, wrong iniciation/polyA signal, whatever) leading to significantly reduced half-life of the mRNA. There may be STOP codon in middle of the gene yielding truncated protein. The protein may have mutated residue loosing all activity.
http://www.biolib.cz/en/main/

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Postby mhwombat » Thu Oct 04, 2012 6:35 pm

Thank you! I was getting confused between pairs of chromosomes and pairs of chromatids. I think I have a clearer mental model now:

Suppose we have a gene G which comes in two forms, G (dominant) and g (recessive), and we have an individual who is Gg (heterozygous in that gene).

Each chromosome has two strands of DNA (chromatids), both of which are *identical*. An individual chromosome contains genetic material from *one* parent.

We have two sets of chromosomes, one from each parent. The chromosomes can be matched up in pairs. The two chromosomes in a pair are said to be homologous. One of those pairs codes for our gene. That is, if we examine one of the pairs, we would find a segment on one of the chromosomes that codes for G, and in the corresponding segment on the other chromosome, we would find the code for g.

The first step of gene expression is transcription, which operates on a single strand of DNA to produce a single strand of RNA. RNA strands don't pair up. So we might look into the cell and see lots of strands of RNA. Some of those strands came from the chromosome pair that we're interested in, and may code for G or g. However, there might be transcription errors that cause g to be omitted, or that cause the strands containing g to have a short half-life, in which case we will mostly only see the G allele. These are two mechanisms that could cause G to be dominant and g recessive.

The next step is translation, which operates on a single strand of RNA to produce proteins. If we examine the proteins in the cells, we might see proteins that will cause the dominant G trait to be expressed, and some that cause the recessive g trait to be expressed. However, the g trait might not get translated, in which case we will only see proteins that lead to the G trait. Also, the g proteins may be inactive. These are two more mechanisms that could cause G to be dominant and g recessive.

Going further back in time, the sperm that carried the g trait may turn out to be slow swimmers, or otherwise faulty. This is another way that G would dominate.

Is this roughly correct?
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Postby mhwombat » Thu Oct 04, 2012 6:40 pm

Also, ova that carry the g allele might be faulty, and might not be released by the ovary, which is another way that the G allele would dominate.
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Postby Cat » Fri Oct 05, 2012 1:15 am

mhwombat wrote:Thank you! I was getting confused between pairs of chromosomes and pairs of chromatids. I think I have a clearer mental model now:

Suppose we have a gene G which comes in two forms, G (dominant) and g (recessive), and we have an individual who is Gg (heterozygous in that gene).

Each chromosome has two strands of DNA (chromatids), both of which are *identical*. An individual chromosome contains genetic material from *one* parent.
...


No. Chromatids are present ONLY during cell division when each chromosome is duplicated and 2 sister chromatids are joined at the centromere. They would be identical to each other IF there was no recombination...

The rest of your reasoning is faulty at best. I’ll try to explain with another example…
Suppose you have two pea plants, one gives green peas and one yellow. They are true breeding because they self-pollinate (“mother” and “father” are one plant). Now you decided to see what happens if they breed together, so you do cross-pollination. Your new generation receives one copy of each chromosome from yellow pea plant and one copy of each chromosome from green pea plant. You discover that ALL of the peas of those plants are Green. So, green is dominant. At that point it’s called a trait locus.

Than you do a lot of research and discover that this locus corresponds to a stretch of DNA on, let’s say, chromosome 6 and it codes for a key enzyme required for production of chlorophyll (green pigment) in the coat of a pea seed (now it’s a gene. Note that trait loci can comprise of more than one gene!)

You also discover that when that yellow pea color gene produces the same enzyme, but a 1000 fold less of it (say due to a point mutation in the promoter). So, when a plant has at least one copy of the “green” allele it produces 1000 times more of the enzyme (more mRNA and more protein) and, thus, a lot more pigment. In the meantime, homozygous plant for the “yellow” allele would lack the green pigment and show the color of the next most abundant pigment – yellow (say carotenoid).

Keep in mind that this is only one example. There is no universal mechanism for this. The key point is that alleles of the gene can differ in a subtle way or drastically on the DNA level – the main difference is in expression. That can be due to different transcription efficiencies (mRNA), mRNA half-life (depends on the length of the 3’UTR. Longer UTR = more protein per mRNA copy), change in coding region (different protein product = different phenotype), etc.
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Postby mhwombat » Fri Oct 05, 2012 3:01 am

Thank you, Cat!
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Postby JackBean » Fri Oct 05, 2012 7:54 pm

Cat: that's basically what we wrote. Except you consider only transcription efficiency and not other possible mechanisms :roll:
http://www.biolib.cz/en/main/

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Re:

Postby Cat » Sat Oct 06, 2012 12:49 am

JackBean wrote:Cat: that's basically what we wrote. Except you consider only transcription efficiency and not other possible mechanisms :roll:


Thant's what you (single) said. Mhwombat wrote the whole story in the next post calling products of two alleles G and g, thus, assuming that gene products are actually different. That is why I wrote up an example where gene product is the same and only transcription level is affected.

Also, mhwombat, your example of sperm etc. describes additional unrelated phenotype...
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Postby JackBean » Sat Oct 06, 2012 8:44 am

IMHO gene includes promotor, thus calling two alleles G and g if they differ in promotor would be IMHO fine
http://www.biolib.cz/en/main/

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Postby mhwombat » Sat Oct 06, 2012 3:58 pm

In my ignorance, I was using the word gene in a very loose sense, meaning a trait of an organism that can take different forms depending on the DNA. It probably would have been better if I had explained from the beginning what I am up to. I do research with artificial life. The way genetics is implemented in artificial life (ALife) is only a very crude approximation of what happens in biology. I'm trying to understand biology a bit better so that I can experiment with making small changes to make the genetics of my ALife critters slightly more realistic. I don't have a background in biology or chemistry, so trying to understand this stuff is definitely a challenge for me.
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Re:

Postby Cat » Sun Oct 07, 2012 3:51 pm

mhwombat wrote:In my ignorance, I was using the word gene in a very loose sense, meaning a trait of an organism that can take different forms depending on the DNA. It probably would have been better if I had explained from the beginning what I am up to. I do research with artificial life. The way genetics is implemented in artificial life (ALife) is only a very crude approximation of what happens in biology. I'm trying to understand biology a bit better so that I can experiment with making small changes to make the genetics of my ALife critters slightly more realistic. I don't have a background in biology or chemistry, so trying to understand this stuff is definitely a challenge for me.


If this project is to create a simulation of evolution, I would be interested in collaboration. Please, let me know by private message.
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