Dory's Biology Questions Thread

[Dory]

#2 Question

Do all amphibians breath through their skin when they're underwater? Also, is there certain percentage of oxygen that we and other animals take in due to skin breathing?

That's an interesting question. I think a lot depends on the water quality, and temperature. Don't forget that many fish can't get enough oxygen from their gills in bad water, and have to come up and gulp air. So I doubt if many amphibians can survive without the odd gulp. They would have to live in very cold, oxygen rich water. But don't forget that a gulp of air goes a long way with cold blooded animals. I seem to remember that crocodiles can stay underwater for an hour, it might be more than that. So an amphibian could probably go a whole day, and only breath air two or three times, if it was getting some oxygen through the skin.
I know they do get some, but it varies from species to species.

I would think that we and other mammals get very little through the skin. Try holding your breath to see.
.

Hmm...interesting.

[GenesForLife]

#3 Question

Are Non-coding RNA evolution's junk?

This question can be split into two parts, Dory, and I'll come back with a detailed lit review for my answers if required, later.

1) Are ncRNAs produced by evolution?

Yes, gene duplication, genome duplication et cetera all basically produce nucleotides , which can be transcribed to produce mRNA
This mRNA, if it has a start codon, is capable of being translated into protein, if it doesn't have one, however, it becomes non-coding.
So that is one way evolution can produce ncRNA.

The other way involves selection acting on extant genes , genes not under selection are free to mutate without harming the evolutionary success of their carriers, this would include duplicate copies of functioning genes, for instance, because they already do have a normally functioning copy and the second copy becomes redundant.
Point mutations that then affect the start codon can convert coding mRNA into ncRNA.

2) Is it junk?

Not always, ncRNA can have loads of functions, ranging from transcriptional regulation to cell signalling to translational regulation, not least because they are capable of interacting with the elements of the genomic processing system.

Let me get started on the literature, please

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151131/

MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression post-transcriptionally. After the discovery of the first miRNA in the roundworm Caenorhabditis elegans, these short regulatory RNAs have been found to be an abundant class of RNAs in plants, animals, and DNA viruses. About 3% of human genes encode for miRNAs, and up to 30% of human protein coding genes may be regulated by miRNAs. MicroRNAs play a key role in diverse biological processes, including development, cell proliferation, differentiation, and apoptosis. Accordingly, altered miRNA expression is likely to contribute to human disease, including cancer. This review will summarize the emerging knowledge of the connections between human miRNA biology and different aspects of carcinogenesis. Various techniques available to investigate miRNAs will also be discussed.

If you are up for it, there are 1000 odd reviews listed on pubmed for ncRNAs , http://www.ncbi.nlm.nih.gov/pubmed

there are around 22000 listings in total and 9008 of those are freely accessible research papers, http://www.ncbi.nlm.nih.gov/pubmed

[Dory]

This mRNA, if it has a start codon, is capable of being translated into protein, if it doesn't have one, however, it becomes non-coding.
So that is one way evolution can produce ncRNA.

Not always, ncRNA can have loads of functions, ranging from transcriptional regulation to cell signalling to translational regulation, not least because they are capable of interacting with the elements of the genomic processing system

.



Interesting. I have a theory they can be very dangerous then. I mean, think about it-- ncRNA may experience mutations (i.e. the DNA that codes for them), but due to lack of start codon, they still cannot manifest. Once they do get a start codon, all the mutations that occurred in them are suddenly manifested! I presume that can be very deadly. What do you think? I mean, I certainly think this statement helps contribute to my theory

Accordingly, altered miRNA expression is likely to contribute to human disease, including cancer

--------------------

If you are up for it, there are 1000 odd reviews listed on pubmed for ncRNAs , http://www.ncbi.nlm.nih.gov/pubmed

there are around 22000 listings in total and 9008 of those are freely accessible research papers, http://www.ncbi.nlm.nih.gov/pubmed

Eep.

About 3% of human genes encode for miRNAs, and up to 30% of human protein coding genes may be regulated by miRNAs.

Woah! That's a significant portion. I'm surprised my textbook didn't mention them.

Thanks GFL, you're a bundle of knowledge as always. My very own e-professor...

[GenesForLife]

If they are indeed deadly, Dory, natural selection will filter them out pretty quickly...

[Dory]

This mRNA, if it has a start codon, is capable of being translated into protein, if it doesn't have one, however, it becomes non-coding.
So that is one way evolution can produce ncRNA.

Not always, ncRNA can have loads of functions, ranging from transcriptional regulation to cell signalling to translational regulation, not least because they are capable of interacting with the elements of the genomic processing system

.



Interesting. I have a theory they can be very dangerous then. I mean, think about it-- ncRNA may experience mutations (i.e. the DNA that codes for them), but due to lack of start codon, they still cannot manifest. Once they do get a start codon, all the mutations that occurred in them are suddenly manifested! I presume that can be very deadly. What do you think? I mean, I certainly think this statement helps contribute to my theory

Accordingly, altered miRNA expression is likely to contribute to human disease, including cancer

--------------------

If you are up for it, there are 1000 odd reviews listed on pubmed for ncRNAs , http://www.ncbi.nlm.nih.gov/pubmed

there are around 22000 listings in total and 9008 of those are freely accessible research papers, http://www.ncbi.nlm.nih.gov/pubmed

Eep.

About 3% of human genes encode for miRNAs, and up to 30% of human protein coding genes may be regulated by miRNAs.

Woah! That's a significant portion. I'm surprised my textbook didn't mention them.

Thanks GFL, you're a bundle of knowledge as always. My very own e-professor...

If they are indeed deadly, Dory, natural selection will filter it out pretty quickly.

But natural selection hadn't filtered out viruses!

[GenesForLife]

Dory, the beneficiality of mutations depends on the carrier of the mutation and the situations present therein, viruses with defective protein coats, for instance, will be outcompeted and outevolved by those which have more infectivity, so, natural selection will eliminate mutations undesirable to the virus and lead to an increasing frequency of beneficial ones, because they can infect better and spread more.

So, all in all, natural selection doesn't act on mutations depending on whether it is deleterious to another organism. , it's every gene for itself.

I should have made that more clear, actually, viruses et cetera are parasites and the selective mechanism itself may be host-dependent, where both the host and the parasite continue to engage in an evolutionary arms race, because mutations in the virus that eliminate hosts too quickly without spread will be removed by selection, and mutations that render viruses unable to infect hosts will be eliminated too, on the other hand, mutations that impair the host's ability to withstand infection will be removed, and those that allow it to resist infections will be selected for.

An example of such a thing happening is the CCR5 delta 32 mutation which confers a very high degree of resistance to HIV.

[Dory]

So, all in all, natural selection doesn't act on mutations depending on whether it is deleterious to another organism. , it's every gene for itself.

Ah, that makes more sense.

because mutations in the virus that eliminate hosts too quickly without spread will be removed by selection,

I do know that viruses best survive by not killing their hosts. That applies to all parasites. *nods*

An example of such a thing happening is the CCR5 delta 32 mutation which confers a very high degree of resistance to HIV.

I lost you at CCR5, but nevermind

[GenesForLife]

So, all in all, natural selection doesn't act on mutations depending on whether it is deleterious to another organism. , it's every gene for itself.

Ah, that makes more sense.

because mutations in the virus that eliminate hosts too quickly without spread will be removed by selection,

I do know that viruses best survive by not killing their hosts. That applies to all parasites. *nods*

An example of such a thing happening is the CCR5 delta 32 mutation which confers a very high degree of resistance to HIV.

I lost you at CCR5, but nevermind

Right, CCR5 is a cell receptor protein that functions in immune system signalling, HIV-1 (one of the two types of HIV and the major variant thereof) uses the CCR5 receptor as a co-receptor, along with CD4 (the antigen characteristic of helper T-cells) to enter cells by endocytosis. Delta 32 is a heritable mutation wherein the transcript of the said protein is 32 base pairs shorter, this prevents the protein being expressed on the cell surface, thus denying HIV an entry, of course, some strains, especially those usually found in advanced stages of the disease, are capable of using another protein called CXCR4 to get in, but those homozygous for the delta 32 variant of CCR5 are also immune against that one because the mutant protein also results in downregulation of the CXCR4 protein and other co-receptors that may be used by HIV.

The following excerpt is from my paper which is currently pending editorial pre-review approval...

The case for reproducing the CCR5 delta 32 phenotype.

HIV/AIDS is a major cause of death in the world [1] , and is particularly problematic due to the absence of a viable cure, throughout history several approaches have been attempted to treat the disease so as to prolong life by reducing viral loads, including Rt inhibitors and Protease inhibitors, often followed by the evolution of viral resistance to the drugs involved, of which a substantial number of responsible genotypic variations exist [2].

It has been demonstrated that individuals who are homozygous for a unique mutant allele involving a 32 base pair deletion in the CCR5 cell receptor allele are resistant to HIV, through a mechanism that prevents the entry of M-tropic HIV strains into CD4+ cells [3].

In a landmark experiment, Hutter et al provided a working proof of concept for the potential of inducing the CCR5 delta 32 phenotype in HIV +ve patients as a method of achieving viral clearance through bone marrow transplantation from a donor homozygous for the relevant mutation [4], however, this approach is medically unfeasible for large scale therapy because of problems with donor compatibility, scarcity of donors possessing the required characteristics and the inherently risks associated with the procedure itself, which involves high failure rates when allogeneic non-identical HLA donors are used [5].

Other approaches such as the use of small molecule blockers of CCR5 have been tried but resistance has been identified as a problem with that particular approach too [6], which supports the case for alternate, genetic methods that seek to reproduce the phenotype.

A simplistic approach could be to silence the resident normal alleles of the CCR5 gene in the CD4+ cells of HIV +ve people , for which a wide variety of antisense oligomers can be designed , but this would only be specific to M-tropic strains which depend on CCR5 as a critical receptor in establishing infection, Hutter et al however, upon induction of the phenotype through transplantation, were able to observe the absence of not only R5 strains but R4 strains as well, which makes the case for not only the resident normal allele to be silenced, but for the delta 32 variant protein to be expressed as well [4].

Agrawal et al have documented the molecular basis by which such a broad spectrum resistance to HIV-1 strains that use receptors other than CCR5 may be seen in carriers of the delta 32 allele, they note that the presence of the defective CCR5 protein also downregulates the expression of other co-receptors [7] .

If you want to do some further reading, here is the list of references for that section of my paper.

References

1. UNAIDS, WHO (2007) , 2007 AIDS Epidemic Update.

2. Johnson VA, Brun-Vezinet F, Clotet B, Gunthard HF, Kuritzkes DR et al (2008) , Top HIV Med. 2008 Dec;16(5):138-45.

3. Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C et al. (1996) Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene, Nature 382, 722−725

4. Hutter G, Novak D, Mossner M, Ganepola S , Allers K et al (2009) Long Term Control of HIV by CCR5 Delta32/Delta32 Stem Cell Transplantation, N Engl J Med, 2009;360:692-8.

5. R Szydlo, JM Goldman, JP Klein, RP Gale, RC Ash et al (1997) Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings , Journal of Clinical Oncology, Vol 15, 1767-1777

6. J P Moore and D R Kuritzkes , (2009) , A piece de resistance: how HIV-1 escapes small molecule CCR5 inhibitors, NIH Public Access Author Manuscript, final edited form published in Curr Opin HIV AIDS. 2009 March ; 4(2): 118–124. doi:10.1097/COH.0b013e3283223d46

7. Lokesh Agrawal, Xihua Lu,1 Jin Qingwen, Zainab VanHorn-Ali, Ioan Vlad Nicolescu et al (2004) Role for CCR5_32 Protein in Resistance to R5, R5X4, and X4 Human Immunodeficiency Virus Type 1 in Primary CD4_ Cells, JOURNAL OF VIROLOGY, Mar. 2004, p. 2277–2287

[Dory]

Woah, so one can develop a better immunity or total immunity against HIV if one contains this mutation?

[GenesForLife]

Woah, so one can develop a better immunity or total immunity against HIV if one contains this mutation?

Nigh on total, the case I talked about in the excerpt (Hutter et al is the paper) involved transplanting bone marrow from a dodor carrying the mutation to a HIV positive recipient , and he stopped taking anti HIV drugs afterwards, but even after a long time (21 months, IIRC, need to dig up that paper again) no virus was detectable in his blood samples or tissue samples, even when high resolution methods were used.

The work that I have presented in the paper involves gene silencing approaches to silence the normal proteins while allowing the expression of the delta 32 proteins, thus replicating the mutation while avoiding the need for bone marrow transplantation et cetera, I cannot reveal the rest of the work until the paper is accepted or rejected, though, but I'm going to tell you it involved a lot of very simple and basic bioinformatics.

[Dory]

Woah, so one can develop a better immunity or total immunity against HIV if one contains this mutation?

Nigh on total, the case I talked about in the excerpt (Hutter et al is the paper) involved transplanting bone marrow from a dodor carrying the mutation to a HIV positive recipient , and he stopped taking anti HIV drugs afterwards, but even after a long time (21 months, IIRC, need to dig up that paper again) no virus was detectable in his blood samples or tissue samples, even when high resolution methods were used.

The work that I have presented in the paper involves gene silencing approaches to silence the normal proteins while allowing the expression of the delta 32 proteins, thus replicating the mutation while avoiding the need for bone marrow transplantation et cetera, I cannot reveal the rest of the work until the paper is accepted or rejected, though, but I'm going to tell you it involved a lot of very simple and basic bioinformatics.

Will you marry me?

[GenesForLife]

Is that a biology question?

[Dory]

Heh.

[GenesForLife]

Heh.

aww , on a serious note I'll help you with career advice and information as long as you need it.

[Dory]

Heh.

aww , on a serious note I'll help you with career advice and information as long as you need it.

You're a sweetheart, I'm definitely taking you up on this as it is.