Question: (Closed) what is the evolutionary importance of existance of cancer gene(s) in other animals than human
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gravatar for Farbod
2.2 years ago by
Farbod3.1k
Toronto
Farbod3.1k wrote:

Hi,

Why other animals same as zebrafish has for example the BRCA1 gene ( that in human is responsible for most case of breast cancer) in their genome?

what is its evolutionary importance ?

and by comparing the human BRCA1 and zebrafish BRCA1 with each other (for example by aligning these two sequence) what can we realize ?

Thanks

genome gene • 1.1k views
ADD COMMENTlink modified 2.2 years ago by genomax55k • written 2.2 years ago by Farbod3.1k
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Humans are not the only animals to get cancer. Dogs and the Tasmanian devil are some examples where naturally occurring cancer is observed. The reason why fish would have a brca1 gene is due to common ancestry. BRCA2 in human and brca2 in zebrafish are orthologues (check the Ensembl list of orthologues for that gene). Whether or not zebrafish will have breast cancer is another story :)

ADD REPLYlink written 2.2 years ago by Denise - Open Targets4.6k
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Dear Denise, thank you for your attention,

Is there any way to find something interesting by comparing the sequences of the BRCA1 gene in several animals and human ? for example in searching for SNPs or comparing the phylogeny trees?

It is some while that I am thinking that it must be some fundamental importance in comparing these kind of genes in an evolutionary perspective (fishes, amphibian, birds, human) but I could not find any related or similar article!

ADD REPLYlink written 2.2 years ago by Farbod3.1k
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This article is good one,

Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals

http://genome.cshlp.org/content/early/2014/01/15/gr.165035.113

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by EagleEye5.7k
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Yes you can investigate the BRCA1 gene (or any other gene) across several vertebrates perhaps even non-vertebrates providing the gene is found across non-vertebrates as well. Ensembl is a good place for that. You will be able to compare the nucleotide sequences of the genomes of 23 amniota vertebrates across the region where BRCA1 is located for example (scroll down on that page to see the actual A, C, G, Ts). You can also get the pairwise alignment between the region where the BRCA1 gene is in human and the counterpart in zebrafish. You can compare the trees for a given gene such as BRCA1. You can also search for a mutation that seems to be associated with cancer e.g. rs139052578 and compare its alignment against the same 23 vertebrates mentioned earlier. These are some papers that can give you a start point so that you can explore further (e.g. Rapid evolution of BRCA1 and BRCA2in humans and other primates, Comparative genomics at the vertebrate extremes, Homologous repair of DNA damage and tumorigenesis:the BRCA connection, Vertebrate pseudogenes. The genes can be investigated in other species than humans where experiments can be carried out. Check BRCA1 in the Target Validation Platform to explore some of the known animal models for the association of this gene with certain diseases and other types of data such as somatic mutations, etc.

ADD REPLYlink written 2.2 years ago by Denise - Open Targets4.6k
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Thanks for your scientific and helpful answer Denise, I know that you spent a lot of time for collecting these interesting links for me, merci beaucoup.

ADD REPLYlink written 2.2 years ago by Farbod3.1k
1

And I have done RNA-seq project on a primitive fish and then I have collect several animal and human BRCA1 sequences from NCBI Nucleotide section and then blastn them against my de novo transcriptome assembly, and then I have fount some hit for BRCA1 which it is not present in ENSEMBL orthologues section, can I add my data to it ?

ADD REPLYlink written 2.2 years ago by Farbod3.1k
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You will only find the orthologues there for the species Ensembl has the genome for (Find a species there). Is your species in that list?

ADD REPLYlink written 2.2 years ago by Denise - Open Targets4.6k
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Dear Dr. Denise,

No, I have worked on sturgeons that are one of the most primitive vertebrates on the planet (living fossils),

the only close related is Gar fish but I have some papers that shows "The common ancestor of sturgeon is the same as the common ancestor or zebrafish (and gar)", So they are equally distant.

Can I use the Ensemble in this case ?

(By the way your answers are really on of my favorites, but unfortunately this topic became a little painful for me)

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by Farbod3.1k
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If you have this sequence that you believe it's a BRCA1 homologue in sturgeon, you can do a BLAST/BLAT search. Blast the sequence against all the fish species (or other vertebrates) in there, e.g. zebrafish, spotted gar, etc and see if it matches any region in any Ensembl genome where a BRCA1 has been annotated. Check the help on how to run the Ensembl BLAST/BLAT tool.

ADD REPLYlink written 2.2 years ago by Denise - Open Targets4.6k
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ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by Farbod3.1k
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A close relative species is on that list. So likely @farbod will find something.

ADD REPLYlink written 2.2 years ago by genomax55k

By the way, I have heard that the only animals that are cancer-free are sharks,

ADD REPLYlink written 2.2 years ago by Farbod3.1k
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Sharks get cancer. The myth that they don't is perpetuated by cigarette manufacturers looking to get into that lucrative shark-market. Probably.

ADD REPLYlink written 2.2 years ago by John12k
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Sharks get cancer but Elephants don't...haha

http://www.nature.com/news/how-elephants-avoid-cancer-1.18534

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by EagleEye5.7k
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If we're covering cancer-free animals, naked mole-rat deserves to go on the list: https://www.sciencedaily.com/releases/2013/07/130731093255.htm

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by Daniel3.6k
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Dear Daniel, Hi and thank you for this interesting link,

and I think Naked mole rats must have a close genetic structure to mouse,

is it true ?

ADD REPLYlink written 2.2 years ago by Farbod3.1k
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You can check out their 'evolutionary distance' here: http://www.timetree.org/search/pairwise/naked%20mole%20rat/mouse

But they're closer to moles than rats I think.

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by Daniel3.6k
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it was very nice, I really appreciate that,

may be some hope for human cancer investigations !

ADD REPLYlink written 2.2 years ago by Farbod3.1k
4
gravatar for Emily_Ensembl
2.2 years ago by
Emily_Ensembl15k
EMBL-EBI
Emily_Ensembl15k wrote:

Genes are not "for causing cancer". Genes are all evolved to have some particular role, which can cause cancer when they go awry. Some "cancer genes" are growth factors, which cause cancer when their activity is increased. Some "cancer genes" are growth restricting, which cause cancer when they become non-functional or under-expressed. They all perform a vital function when behaving normally.

If we look at the GO terms associated with BRCA1 we can see that it is involved in DNA replication and repair – vital functions. But it's also clear how damage to these processes would lead to cancer, as faulty DNA-repair mechanisms would increase the mutation rate.

BRAF is mutated in 80% of melanomas. Indeed, the simultaneous mutation of BRAF and TP53 can trigger melanoma with no other mutation, and this has been modelled in zebrafish, so this is not just a human mechanism. But BRAF isn't just a "cancer gene", it's necessary for signal transduction and development. TP53 is, arguably, a "cancer gene" because its role is to keep a check on cell division, causing apoptosis in cancerous cells.

The only reason humans get more cancer than other animals is that technology has led to better nutrition and medicine, meaning we live longer and don't tend to die of other things, like starvation and infection. You live long enough, you get cancer.

ADD COMMENTlink modified 2.2 years ago • written 2.2 years ago by Emily_Ensembl15k
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Dear Dr Emily, I wish you a happy long but cancer-free life!

But could you please offer me some guidance about the value of comparing these genes in different animals or introducing me with a similar paper, too?

ADD REPLYlink written 2.2 years ago by Farbod3.1k
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No idea. Just making sure that you understand that no gene has the function of "causing cancer", and therefore should be present in other species.

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by Emily_Ensembl15k
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Be sure that I knew that, dear.

I was searching for some interesting idea about the "comparison" that I have been mentioned several times in this topic. For example I have researched about epigenetic effects on cancers and it seems that for example hypermethylation of CpG island shores of BRCA1 has some role in its cancer-producing status, but usually there is no such epigenetic manner in for example zebrafish, and when I compare these two sequences, of course there are some strong homology, but it is not 100% and I guess that those differences may be is a factor for managing cancer! just an idea and I have asked it here to hear some guidance from expert persons like you.

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by Farbod3.1k
3

Please do not call people "dear" Farbod. I don't know if English is your first language or not, but these days that sounds quite rude. I'm sure you didn't mean it to be rude, but regardless it sounds very.... uncomfortable -- particularly after Emily put a lot of time into writing you such a great answer :)

Reading the rest of your post, I think you missed Emily's point that genes like BRCA1 don't cause cancer, as in that is their primary purpose in life. Often they either are genes that cause cells to proliferate - a very useful function that if over-used can cause cancer - or, like BRCA, they are checkpoint proteins that actively prevent cancer, so only when these genes are mutated you get cancer. The first class of genes are "oncogenes", the second "tumor suppressor genes", and both come under "cancer related genes". It's important to remember that many genes are named for the phenotype exhibited when you lose the gene, not what the gene does in the normal state. For example, the gene 'white' causes red eyes in drosophila. It was named 'white' because that's what you see when you knock it out (this is the sort of thing I was referring to in the other post about biggest challenges for bioinformatics in the future being managing complexity. Biologists don't make it easy eh).

The question about looking for variations between homologs in different species is a tough one to answer. It really depends on the two species you're looking at, because the more distant the two species are the more likely the gene has totally different functions in the two species. Humans, for example, have a 'white' gene homolog called ABCG1, but it doesn't give us red compound eyes like drosophila! Instead, its used for fatty acid/cholesterol transport.

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by John12k
4

John, English is not my maternal language but I have used "Dear" as possibly all we have learned it in primary school or letter writing classes expressing this meaning " http://dictionary.cambridge.org/dictionary/english/dear" and it is for the first time that I am hearing that "using dear" = "being rude" ! by the way, I have shows my appreciation in each reply as "Dear Denise, thank you for your attention" or "Dear Dr Emily, I wish you a happy long but cancer-free life!" and sorry if there is not any other way in this website to pay for the "lots of time" that people are spending voluntary to help others.

ADD REPLYlink written 2.2 years ago by Farbod3.1k
3

OK, quick English lesson. "Dear name" as a greeting to start a letter is correct, although it is probably a bit formal for BioStars.

Using "dear" as a generic way to refer to someone mid-sentence is a term of endearment, and words such as "love", "sweetheart", "honey", "duck" and many more can also be used in the same way, depending on what part of the English-speaking world you come from. Generally, these are used by someone close to you, such as a family member, and are generally affectionate. They can also be a bit of a verbal tic, that some people use to talk to anyone they don't know – without going into hideous historical detail about the English class system and different regional accents, suffice to say such verbal tics are usually associated with lower status individuals. As such, when someone uses a term of endearment to refer to a seemingly high status individual, it is often seen as trying to demonstrate one's higher status over that individual. This is particularly true when the term is written down, as most people do not have verbal tics when writing, only when speaking, or when spoken in an accent that does not match the region where the term is generally used.

To compare with other languages, using "dear" other than to start a letter is equivalent to calling someone "tu" (informal you) in French. You would use it for close friends and family, but if you use it for someone you don't know you are implying a higher social status than that person.

The nuance of language, of course, not obvious to a non-native speaker, and someone can be forgiven for not knowing this. I think that English lessons abroad can teach things that are incorrect or misleading. As a woman, I find letters/emails to "Dear Sir" (should be "Dear Sir/Madam") or documents that refer to an unknown third person as "he" (should be "they") pretty offensive, however I am aware that in many countries people are taught that this is "correct", so I try not to let it bother me.

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by Emily_Ensembl15k
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Thanks John. I think it is rude, both to say "I knew that dear", but also to respond to an answer to one of a person's questions with "OK, but I also asked this question and do you personally know the answer to that?". I answered the question I knew the answer to, I'll leave it to someone else to help with the other questions. Answering part of someone's question does not oblige you to then become their personal helper with all their questions.

I think the nature of bioinformatics is such that people often come in from a biological perspective and need to learn the computer stuff, or come in from a computing perspective and need to learn the biology, which can lead to some very naive questions on both sides. I read this as a naive biological question, likely affected by misleading news reporting like "Angelina Jolie has the BRCA1 gene, so is at risk from breast and ovarian cancer" (she does have the BRCA1 gene, two of them in fact, and so do I, but mine are normal (probably, no breast cancer in my family) and won't give me cancer), and answered it accordingly. Perhaps I was wrong in my reading of the question, but that doesn't excuse rudeness.

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by Emily_Ensembl15k
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Hi, I am very very sorry that you feel something "not-good" from my replies, I really do not mean that as I look at the life and the world as a short period of being in physically format and I do not intend to say anything rude to anyone specially the one that is helping me in this short period, may be my try to just make it as short as possible to reply made it worst. and would you please tell me that from where did you assume this :" to respond to an answer to one of a person's questions with "OK, but I also asked this question and do you personally know the answer to that?" I never ever mean that !

ADD REPLYlink written 2.2 years ago by Farbod3.1k

"But could you please offer me some guidance about the value of comparing these genes in different animals or introducing me with a similar paper, too?" addressed specifically to me.

"Is there any way to find something interesting by comparing the sequences of the BRCA1 gene in several animals and human ? for example in searching for SNPs or comparing the phylogeny trees?" addressed specifically to Denise.

ADD REPLYlink written 2.2 years ago by Emily_Ensembl15k
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Emily_Ensembl, it was addressing to you because clearly it was you that was trying to help me at that moment and I was (and am) really appreciate that. I do not get the point that which part of it was impolite to you as I imagine you and other biostar members as my dear teachers and friends ! you have told me about this concept that BRCA1 is not a cancer gene, and you have told me that the long life time of the modern human being make it more possible to get cancer, I accept that and I have begin my reply with the pray for your everlasting health and happiness (maybe that make you feel angry?sorry but it was with full honest) and then I beg you to help me about this matter that how we can make some comparison of sequence and if they are a logical approaches beginning with , "But, (could you or would you please kindly help me and as you have guide me from the first part of question, help me for the second part too please) .

imagine that for example I have asked you that where is the post office and where is the police station and you told me that the post office is there, and I asked again (politely I guess) But would you please help me about the police station address, Too, please?

then you have told "Just making sure . . . " Then I have used "Be sure that I knew that, dear." By that I mean that Dear (sorry to use this rude or " to refer to a seemingly high status individual" word) Emily, Be sure that I have learned scientific concepts that you have teach me about BRCA1 is not a "cancer gene" but a gene that can become . . . . - - - > I used a past verb "knew" for this aim and then ",dear" (that it means you are a dear person or dear teacher or dear helper to me) was for closing my sentence. I do not know which part of it was "bad words"

and I do not know that what that means by "addressed specifically to Denise" ? is she angry, too? sorry Denise.

sorry for all my questions and answers and bad English and bad biology and thank you for elementary English lessons and calling me "double rude". . . . it is enough for me, and I will leave this question.

I have seen many many questions in the Biostar and SeqAnswer that begins with no hello and no thanks and no dear and no appreciation and no Sincerely, may be it is a best strategy! but I dont like it !

ADD REPLYlink modified 2.2 years ago • written 2.2 years ago by Farbod3.1k
1

and I do not know that what that means by "addressed specifically to Denise" ? is she angry, too? sorry Denise.

No, I'm not angry Farbod.

ADD REPLYlink written 2.2 years ago by Denise - Open Targets4.6k
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OK Farbod, I think it's clear that you didn't mean to insult anyone and you were genuinely trying to be nice. Since your question has been answered I think it's for the best if we close this thread for now and you open a new one if you have any other questions in the future.

If you wish to discuss topics rather than get a specific answer to a specific question, make sure to tag your post as "Forum" and not "Question". Forum posts generally are a bit longer and people do ask follow-up questions like you asked Emily, but for Question/Answers threads it is expected that people will write as much as they can in their answer the first time, and follow-up questions are rather unusual.

Final point, Biostars isn't a resource for learning written English etiquette but http://english.stackexchange.com/ is. You might want to ask people there what you could have done differently here. Good luck! :)

ADD REPLYlink written 2.2 years ago by John12k
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It might be that you were looking for an idea about comparison, but that didn't seem to be the focus of your question. By comparing the BRCA1 sequences of zebrafish and human you can find... differences. Interpretation will be harder. You could try to look for functional domains which are different, but any conclusions about cancer in zebrafish/human will be pure speculation.

Why other animals same as zebrafish has for example the BRCA1 gene ( that in human is responsible for most case of breast cancer) in their genome? what is its evolutionary importance ?

Questions like these make me doubt your biological background/knowledge. Maybe you should get that fixed before starting with more difficult questions. "Be sure that I knew that, dear." -> That wasn't obvious from your question, and the explanation given by Emily was excellent. Your RNA-seq will not tell you anything about epigenetics, hypermethylation, CpG islands shores,... because it's RNA-seq.

ADD REPLYlink written 2.2 years ago by WouterDeCoster32k
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(I really doubt how to began my reply, not being rude - I usually begin with something like: Dear WouterDeCoster) - Thank you and the RNA-seq was used to find some homology between primitive vertebrates transcripts and some human cancer genes, not of course for epimutation researches. My biology is as my English, sorry :)

ADD REPLYlink written 2.2 years ago by Farbod3.1k
2

I'm not a native English-speaker myself, don't worry. Bioinformatics is at the strange intersection of informatics and biology (and some other fields), so it's hard to have a deep understanding of both. But at the same it's vital for performing your research.

ADD REPLYlink written 2.2 years ago by WouterDeCoster32k

Your first question was to ask why zebrafish would have cancer genes.

ADD REPLYlink written 2.2 years ago by Emily_Ensembl15k
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Hi, and thank you a thousand time, I know that you are a really busy scientist and I really appreciate from the deepest part of my heart for the time that you are spending answering me . by the way, I did not ask about "why zebrafish would have cancer genes" but "why zebrafish would have BRCA1 genes" and what is its evolutionary purposes that there is some change in its characteristics in human! Thank you again for your full answer

ADD REPLYlink written 2.2 years ago by Farbod3.1k

I, er - maybe we just do the 1 British-English etiquette lesson a day? He won't take it to heart if every effort to make amends winds us up even more :P This is working on the assumption that it is purely a language issue.

ADD REPLYlink written 2.2 years ago by John12k
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I believe how to properly communicate is at least as important as how to do your scientific research. Assuming that this is just the consequence of being uncomfortable in English, we maybe should try to get back to the biological question :-)

@Farod: I see you haven't added your location to your biostars profile. Perhaps that might help, to let people know that English is not your first language.

ADD REPLYlink written 2.2 years ago by WouterDeCoster32k
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How about those like me who are not native English speakers but live/work in an English speaking country? ;)

ADD REPLYlink written 2.2 years ago by Denise - Open Targets4.6k
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