Luxury genes and epigenetics

[icakeov]

Are luxury (smart) genes a direct result of epigenetics?

I don't really see these two terms used together in articles that I come across. I just wanted to confirm whether they are in fact, directly linked?

Since hemoglobin gene is expressed only in red blood cells, this would make this gene a luxury gene, and in the same token, it would be a regulated epigenetic expression, right?

Thanks for any feedback

 

[jedishrfu]

It seems the regulation of the genes is a result of having food or not having food. So in the case of hemoglobin isn't that something you need all the time for breathing.

This paper talks about deer and how feeding availability affects their antler growth so it would seem antlers are a luxury:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127705/

 

[icakeov]

Thanks for the feedback jedishrfu, I guess I am also trying to figure out the terminology too. Perhaps luxury gene is different from luxury phenotype?
This video uses hemoglobin as an example of luxury gene expression:

 

[BillTre]

By luxury genes you mean non-housekeeping (or regulated) genes.
Housekeeping genes might be defined as: on in (almost (mature human red blood cells would be an exception)) every cell, involved with basic processes of cell maintenance and structure.

Epigenetic = Heritable phenotype changes that do not involve alterations in the DNA sequence?
Perhaps like histone modifications that are propagated?

Are luxury (smart) genes a direct result of epigenetics?

Not all.
Gene expression in the body can be controlled without using non-sequence based inheritance systems.

There are lots of gene expression control systems based on binding of proteins or groups of proteins to specific DNA sequences that are dynamic molecular structures and not inherited in some on-or-off state. This would be the most common way this is done.

Could some gene regulation use a mechanism like DNA associated inheritance of a developmental state without sequence change?
Yes. Some developmental processes can be explained with such systems:
Examples: Polycomb affects Hox gene expression and is involved in X-chromosome inactivation.
It changes the chromatin structure (the way the DNA is packaged on molecularly, affecting access by proteins and thus gene regulatory influences) and is inherited by all of each cell's progeny.
In X-chromosome inactivation, early in development one of a mammalian female's two X-chromosomes are randomly inactivated.
This state is then inherited by all of each cell's progeny (a clone of cells founded by the cell in which the initial change occurred).
In Hox gene control (different molecular gene controllers expressed in different body locations), expression levels of several control genes, using similar molecular mechanisms, are similarly set (but in this case based upon body position) and then inherited by all of each cell's progeny.
Hox genes are set in a particular order from head to tail to correspond with location along the body axis.
Together, the Hox genes make a combinatorical code for body location.
This is set early in development and the body parts develop from cells according to their settings.

In some cases, these non-sequence modifications in gene expression can be inherited by the next generation.

 

[icakeov]

Many thanks BillTre,
That clarifies a lot, I thought that luxury genes directly implied epigenetics (or vice versa).

In X-chromosome inactivation, early in development one of a mammalian female's two X-chromosomes are randomly inactivated.

So in essence, a "random event" can create a regulation, rather than a specific environmental epigenetic influence.

In some cases, these non-sequence modifications in gene expression can be inherited by the next generation.

So a "random event" like the one above can plausibly end up getting inherited, which would then make it "epigenetic"?

 

[Ygggdrasil]

It's important in this discussion to clarify what is meant by the terms "epigenetic" and "epigenetics." Many people define the term differently, to the point that the term is almost meaningless. See, for example, these various discussions of the issue:

Over the past few years we have seen an odd change, or extension, in the use of the word ‘epigenetic’ when describing matters of gene regulation in eukaryotes. Although it may generally be that it is not worth arguing over definitions, this is true only insofar as the participants in the discussion know what each other means. I believe the altered use of the term carries baggage from the standard definition that can have misleading implications.

https://www.sciencedirect.com/science/article/pii/S096098220701007X

Interest in the field of epigenetics has increased rapidly over the last decade, with the term becoming more identifiable in biomedical research, scientific fields outside of the molecular sciences, such as ecology and physiology, and even mainstream culture. It has become increasingly clear, however, that different investigators ascribe different definitions to the term. Some employ epigenetics to explain changes in gene expression, others use it to refer to transgenerational effects and/or inherited expression states. This disagreement on a clear definition has made communication difficult, synthesis of epigenetic research across fields nearly impossible, and has in many ways biased methodologies and interpretations.

http://www.genetics.org/content/199/4/887

The term epigenetics in its contemporary usage emerged in the 1990s, but for some years has been used in somewhat variable meanings.[8] A consensus definition of the concept of epigenetic trait as "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence" was formulated at a Cold Spring Harbor meeting in 2008,[4] although alternate definitions that include non-heritable traits are still being used.[9]

https://en.wikipedia.org/wiki/Epigenetics#Definitions

 

[icakeov]

That is so helpful Ygggdrasil! I had no idea it had two meanings but not surprised. These days it seems with the advantage of the amount of information, everything has more than one knowledge. My adjectives vocabulary is really getting exercised.

The "main" definition would then be something along the lines:
A creation of a phenotype that is (or can be) heritable (and not random), and the change is thus genetically influenced, even if not directly by the gene sequence (but some emergent construct of the genes), and it doesn't involve any mutation.

Furthermore, luxury genes don't have to be created through this epigenetic "regulatory mechanism", they can actually be non-heritably created as well.

I hope I got it all more or less right. Thanks again for all your input!

 

[icakeov]

I have another question that ties into this topic:

Seems like the concept of epigenetics can exist in both unicellular and multicellular organisms (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973776/)

Can the same be said about luxury genes, or is the concept of a luxury gene only sensical in the context of a multicellular organism (or perhaps even a colony of bacteria, or some "pluri-cellular" environment)?

I did find that luxury genes can be "plasmids of bacteria and genes coding for heat-shock proteins", so it seems it quite exists in unicellular organisms too.
https://www.biology-online.org/dictionary/Luxury_gene

 

[BillTre]

Can the same be said about luxury genes, or is the concept of a luxury gene only sensical in the context of a multicellular organism (or perhaps even a colony of bacteria, or some "pluri-cellular" environment)?

I am not familiar with the term luxury genes, but it seems it means non-housekeeping genes.

• Housekeeping genes would be "on" in most (there's always some weird exception) cells in the animal.
  
• So non-housekeeping (luxury genes) are all the others that are turned on and/or off at different times.

For development to happen correctly, the luxury genes would have to be turned on and off in some orchestrated manner.
Many genes are known to be turned on and off at different stages (or times) in development.
Developmental applications of transcriptomics look at differences in total gene expression of many different cells (ideally, all the transcripts in different types of cells can be collected) to follow cells through development.

What about Housekeeping-ish genes that have: multiple copies of almost the same gene but with slight differences, and are expressed in different tissues?

Some single cell organisms can have in essence multiple cell types as they progress through the different stages (or optional states) of their life cycle.
For example, among different species of Choanoflagellates (thought to be our closest relative outside of the multicellular metazoans) have the following traits:

• some have asexual or sexual reproduction
• some can be colonial or not
  
• some can be free swimming or adherent to a substrate
• some can form spore stages

These are functionally adopting different cells types that express different sets of genes for their different purposes.
The sets of expressed genes generate the cellular structures and behaviors appropriate to their situation at that time.
These regulated genes determine what the cells do in many ways, including what alternative gene expression sets they or their progeny could express.

This is thought to be a possible reason developmental regulatory genes are found in single celled choanoflagellates.
The adaptive explanation for why those genes are in choanoflagellates would be that the developmental regulatory genes are involved in regulating gene expression patterns to generate different cell structures and functions appropriate to their current situation.
Some of the choanoflagellate's regulatory genes would be available for metazoan evolution to reuse in various different situations.

Choanaflagellate gene regulation could be pretty complex. Other non-metazoan organisms could similarly complex.
Certainly, it is in multi-cellular animals (metazoans).
Bacteria (much simpler cells) express different genes at different times, such as producing an enzyme when some substrate molecule is around.
Bacteria, either as a colony of bacteria with cells in the interior or on the surface, or floating around, or forming a spore might well have groups of different genes on in different situations. They want to be (have been selected to be) efficient.

 

[Ygggdrasil]

I have another question that ties into this topic:

Seems like the concept of epigenetics can exist in both unicellular and multicellular organisms (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973776/)

Can the same be said about luxury genes, or is the concept of a luxury gene only sensical in the context of a multicellular organism (or perhaps even a colony of bacteria, or some "pluri-cellular" environment)?

I did find that luxury genes can be "plasmids of bacteria and genes coding for heat-shock proteins", so it seems it quite exists in unicellular organisms too.
https://www.biology-online.org/dictionary/Luxury_gene

In bacteria and other unicellular organisms, the "luxury genes" that are expressed only in some conditions but not others would be better known as inducible genes. The classic example in bacteria would be the lac operon, which encodes a set of genes involved in the metabolism of the sugar lactose. Under normal conditions, when glucose is present, bacteria will prefer to eat glucose. However, when glucose levels are low and lactose is present, the bacteria will switch on the lac operon to allow the bacteria to begin eating the lactose. Most molecular biology textbooks will have a good discussion of the lac operon and other inducible operons in bacteria (e.g. the trp operon).

Interestingly, at intermediate concentrations of lactose, the transcriptonal state of the lac operon (whether it is turned on or off) can be inherited epigenetically (i.e. two genetically identical bacteria in the same environment can show different phenotypes based on the different histories of the bacteria), and there are good mathematical models explaining this phenomena (e.g. https://www.sciencedirect.com/science/article/pii/S0006349507711839).

Regulation of inducible genes in yeast (which are eukaryotes and much more closely related to animals than bacteria), may provide a better model for thinking about gene regulation in humans, as some of the same mechanisms involving histone mobilization and modification are involved. Various sets of inducible genes have been extensively studied in yeast (e.g. genes that turn on in response to osmotic shock, changes in carbon source or phosphate starvation). Many of these systems are discussed in cell biology or molecular biology textbooks.

 

[icakeov]

Incredibly helpful! Thank you for all this feedback!

 

[icakeov]

If I may do another follow up question:
Do housekeeping genes ever get epigenetic tags marking them?
Would it be that they do and that they are always turned on? Or more that the gene is not unexpressed because there are not epigenetic tags to interfere?

 

[Ygggdrasil]

If I may do another follow up question:
Do housekeeping genes ever get epigenetic tags marking them?
Would it be that they do and that they are always turned on? Or more that the gene is not unexpressed because there are not epigenetic tags to interfere?

Various histone modifications are associated with actively transcribed genes, such as tri-methylation of H3K4 at promoters and tri-methylation of H3K36 over gene bodies. There is debate about the whether these histone modifications are the cause of active transcription or whether they are merely an effect of active transcription (which is generally a question about the roles of most histone modifications).

Other histone modifications, (such as tri-methylation of H3K27 or tri-methylation of H3K9) are associated with gene repression, so depending on the type, histone modifications can be associated either with gene activation or gene silencing.

DNA methylation at promoters is generally associated with gene silencing, though DNA methylation over gene bodies is associated with highly expressed genes (like housekeeping genes), so the connections between DNA methylation and gene expression are context dependent.

 

[icakeov]

Another question came to mind:

Are there examples at all, of organisms that don't actually have some type of tagging processes such as epigenetic tagging?
In other words, can an organism even exist without some "on"/"off" tags that for example, would help design cell components in unicellular organisms, "telling" genes where to even locally be expressed and where not? Or is there a different process that "regulates" the building of cell components?

Again, any thoughts appreciated!

 

[Ygggdrasil]

Another question came to mind:

Are there examples at all, of organisms that don't actually have some type of tagging processes such as epigenetic tagging?
In other words, can an organism even exist without some "on"/"off" tags that for example, would help design cell components in unicellular organisms, "telling" genes where to even locally be expressed and where not? Or is there a different process that "regulates" the building of cell components?

Again, any thoughts appreciated!

As far as I know most organisms have some form of DNA or histone modification, but these tagging systems don't always play roles in epigenetic regulation (i.e. regulating gene expression programs across cell divisions). This is why it is problematic to keep referring to DNA and histone modifications as "epigenetic tags."

A good example here is bacteria. Bacteria, being prokaryotes, lack histone proteins, so they do not have the same histone modification machinery that eukaryotic cells use to regulate gene expression. Bacteria do have DNA methylation machinery to methylate adenine residues to N⁶-methyladenine (6mA). However, in bacteria, 6mA does not play major roles in regulating gene expression; rather, it's most important roles are in DNA repair (enabling the cell to distinguish between the methylated parental strand and the unmethylated newly synthesized strand when correcting mutations that arise during DNA replication) and in antiviral defense (enabling the cell to distinguish between its own methylated DNA versus unmethylated, foreign DNA).

Bacteria are still able to stably turn genes on and off and switch between various cellular states (as discussed above in post #10). Thus, epigenetic regulation of gene expression does not need to involve DNA or histone modifications (another reason why it is problematic to refer to these modifications as "epigenetic tags").

 

[icakeov]

Thank you Ygggdrasil. That really clarified it!

 

[icakeov]

So "epigenetics" is a word that is primarily used to "gene expression regulation" that is inheritable? This would make the "epigenome" all the compounds that constitute the inherited "gene expression" modifications, but that leaves out the "gene regulation" compounds that "regulate" but are not necessarily part of the "epigenome"?

Is there a word such as "epigenome" that would refer to all the compounds that are involved in "gene expression regulation"? "Regulatory genome"?

I hope I am not missing the mark on this one.
(This might indicate that the title of this thread would have been less confusing if I had used the word "gene regulation" rather than "epigenetics"?)

 

[Ygggdrasil]

IMHO, there are so many definitions of the word epigenetic that it is essentially a useless buzzword that confuses the general public (and many scientists!). See the articles linked in post #6 for a few articles discussing the various ways people use the word "epigenetic." Whenever people throw around the word "epigenetic" it is worth seeing exactly what definition they are referring to, and whether they are confusing the two definitions (e.g. just because histone modifications are called "epigenetic" modifications, they assume that these modifications are necessarily mediating the inheritance of gene expression programs across cell division [a more traditional definition of the word "epigenetic"]).

The terms "epigenome" and "epigenomics" typically refer to mapping DNA methylation and histone modifications across the genome. While these modifications are associated with transcriptional regulation, the causative link (and direction of the causation) between the two is still somewhat unclear.