Talk:Melanocortin 1 receptor

Mc1r v. MC1R

Subject line says it all - this article uses Mc1r, but some of the references at least use MC1R - which is correct? Rachel Pearce (talk) 11:32, 26 February 2008 (UTC)

Genetics image

I have removed the image of the map of human skin colours over the globe as it is misleading and irrelevant to the topic (we're discussing the 1-4% of the population with a dysfunctional MC1R variation, not the evolution of skin colour in the general population).

There is however a more relevant image of the distribution of red hair in the United Kingdom at http://anthro.palomar.edu/vary/images/map_of_red_hair_in_England.gif (the HTML it's used in is http://anthro.palomar.edu/vary/vary_1.htm) that maybe should go in its place. The image is "reproduced with permission from Cambridge University Press. From E. Sunderland, "Hair-Colour in the United Kingdom," The Annals of Human Genetics, Vol. 20, p. 327, 1955-56", the original article can be found here: http://onlinelibrary.wiley.com/doi/10.1111/j.1469-1809.1955.tb01286.x/abstract but you have to pay to see the whole thing.

Can someone either get permission and upload it, or tell me how to go about it. Tobus2 (talk) 01:09, 26 January 2011 (UTC)

Dental pain in humans

I believe the prevalence of people with MC1R who have a GREAT deal of pain during dental procedures is relevant to this article (apparently it confers immunity to anesthetic).

http://jada.ada.org/content/140/7/896.abstract http://articles.cnn.com/2009-07-30/health/redhead.pain.dentist_1_red-hair-thermal-pain-redheads?_s=PM:HEALTH http://wiki.riteme.site/wiki/Outcomes_Research_Consortium#Red_Hair_and_Anesthesia — Preceding unsigned comment added by Dianaramadani (talk • contribs) 09:40, 20 January 2012 (UTC)

Red hair and freckles

The last part in the function section says "People with freckles and no red hair, have an 85 percent chance of carrying the defective MC1R gene that is connected to red hair, and the red hair gene. People with no freckles and no red hair have an 18 percent chance of carrying the MC1R gene linked to red hair." Granted, citations are needed for these statements, but what are the percentages of carrying the gene with both red hair and freckles? — Preceding unsigned comment added by 67.142.172.21 (talk) 18:48, 9 May 2012 (UTC)

While this is an old post, that is still the structure of the paragraph, and while I was checking out the source I wondered why we're trying to demonstrate prevalence using that data mentioned above, and not using this data from the abstract - that's not behind a pay wall.

We now report the presence of MC1R gene sequence variants in humans. These were found in over 80% of individuals with red hair and/or fair skin that tans poorly but in fewer than 20% of individuals with brown or black hair and in less than 4% of those who showed a good tanning response.

Even if those numbers about "freckles but no red hair" are accurate - as I can't read the full study I have no way of knowing - I feel like the information in the article now is trivial (as in non-encyclopedic factoids), and is showing outliers not prevalence.

Is there anyone who has access to the article, that provide more context for the details the article is currently using? Because that context might make these numbers more useful. But if not, I'm inclined to rewrite that section focused on the facts in the excerpt I put above. CleverTitania (talk) 01:46, 1 September 2018 (UTC)

It's on sci-hub — Preceding unsigned comment added by 124.171.167.171 (talk) 02:30, 1 September 2018 (UTC)

I removed the actual link to the article posted by 124.171.167.171 as we are not allowed to link to articles there. DMacks (talk) 07:10, 14 October 2018 (UTC)

Am I missing something or is the information in that paragraph not remotely in this study? There is one mention of freckles in passing, and none of the skin types they were studying - which is one of the key data points the entire study is built around - specifically include or exclude freckles. Yes, Type I mentions freckles on the Fitzpatrick_scale Wiki page, but it's not saying only Type I has freckles or is pale. And people with any of the skin types can still have freckles - unless Morgan Freeman is considered to have Type I skin. And even if the person who wrote the paragraph created it from extrapolating information on one of more of the skin types specifically, I can't find any math in the tables or figures given in that study to match the numbers of 85% or 18%. So anyone have any idea why this document is being used as a reference for the data that's currently in the article? CleverTitania (talk) 22:48, 1 September 2018 (UTC)

According to page history I'm the one who added that ref, to fix a cn for an edit made 2 years earlier by an IP. No idea what I was thinking at the time, but probably mistook the wording on the article and matched it to the "over 80%... fewer then 20%" in the abstract. What we currently have in the article seems pretty silly - reporting the prevalence of the "red hair" gene in people who *don't* have red hair (except perhaps to show it is recessive?). I'm happy for you to rewrite using the info in the ref's abstract. Tobus (talk) 02:27, 2 September 2018 (UTC)

removal of negative wording

I removed reference to the gene expression being negative 'defective' as it is probably not.

Mesolithic

The claim that there is "no evidence is known for positive selection of MC1R alleles in Europe... and no evidence of an association between MC1R and the evolution of light skin in European populations" is patently false. It appears to be based on old studies, from well before most European populations were examined for MC1R alleles. Many analyses have since been conducted, and it is now established that European populations indeed have among the highest frequencies of the MC1R gene's derived rs8045560 allele, which is associated with light skin pigmentation. It has also been found that the Khoisan have high frequencies of this variant; this in turn may largely explain their oftentimes pale complexion and fair hair color. In fact, scientists have now observed MC1R alleles like rs1805008 (which is associated with red hair & fair skin) in various prehistoric European groups, such as among Mesolithic Motala specimens dating from around 8,000 years ago (e.g. Lazaridis et al. 2013 [1]). Also, the Portuguese study that was linked to doesn't contain the allele frequencies. It just points out that MC1R alleles are associated with variations in pigmentation, a bland fact [2]. The actual frequencies are contained on the Allele Frequency Database (ALFRED) managed by Kenneth Kidd's Yale University lab, with the individual samples in the links there [3]. Soupforone (talk) 13:41, 24 June 2016 (UTC)

The following primary peer viewed sources: PMID 11305330, 1288200, 17182896 were replaced by

• PMID 25230663 and
• Rodenbusch, Rodrigo A. (2014). Análise de SNPs em Genes Dde Pigmentação Humana em Indivíduos com alto ou Baixo Conteúdo de Melanina [SNP Analysis in Human Pigmentation Genes in People with High or Low Melanin Content] (Ph.D.) (in Portuguese). Catholic University of Rio Grande do Sul.

The first source is also primary peer reviewed article and more recent, hence it is an acceptable source. The second source however is a Ph.D. thesis which has not undergone independent peer review, hence its use is questionable. The rest of your reasoning does appear to be sound, however also appears to be original research. What is needed are recent secondary sources (review articles). Boghog (talk) 15:07, 24 June 2016 (UTC)

Here are two reviews, PMID 15979202, 19297406, but they are not as recent as one would like. Boghog (talk) 15:25, 24 June 2016 (UTC)

The claim that "no evidence is known for positive selection of MC1R alleles in Europe" was from a 16 year old paper by Harding et al. [4]. The claim that there is "no evidence of an association between MC1R and the evolution of light skin in European populations" is from the more recent Norton et al. [5]. However, both are clearly inaccurate for the reasons explained above - various MC1R alleles have been found in both recent and ancient/Mesolithic European specimens. The Portuguese paper does not pertain to these assertions; it just points out that MC1R alleles are associated with variations in pigmentation, like the NIH link above. With regard to the actual allele frequencies, they are linked via ALFRED. For example, for Tuscans, the allele frequency is from Rosenberg et al. (2002) sample [6]. Soupforone (talk) 16:04, 24 June 2016 (UTC)

I agree with Boghog, the changes are OR in that they lead to a conclusion that isn't stated in any source (and one that seems wrong to me).

- The age of the studies is irrelevant if they haven't been refuted - if there is a published peer-reviewed source that says MC1R a) has been positively selected for, or b) is associated with the evolution of the modern European phenotype, then all you need to do is link to it.

- I looked, but didn't find any research that links rs8045560 to skin colour, perhaps can you provide some sources? Typically MC1R is associated with minor variation within "white" European populations (ie pale/non-tanning skin, freckling), rather than differences between African and European populations.

- The MC1R alleles reported for Motala in the Laz. "3 pops" paper are the same ones reported for Loschbour and Stuttgart (Table S8.1) so I'm not sure why you are singling that sample out.

- The frequencies in Alfred aren't indicative of positive selection - compare frequencies with SLC24A5, SLC45A2 and LCT which *were* positively selected for.

- The 2015 Haak et. al. paper "8000 years of natural selection in Europe" [7] features a GWAS for alleles under selection in European pops from the Mesolithic to today... MCR1 was not detected. (see Fig. 2)

Tobus (talk) 16:33, 24 June 2016 (UTC)

The two assertions in a) & b) above are from separate analyses. They are also inaccurate - please see for example Savage et al. 2008 [8] ("This study further quantifies the degree of population-specific genetic variation and suggests that positive selection may be present in European populations in MC1R" -- "Numerous studies have demonstrated associations between specific MC1R variants and red hair, light skin, poor tanning ability and heavy freckling"). With regard to the Motala Mesolithic tombs, the point was to give an example of one such prehistoric population, but Loschbour and Stuttgart are okay too. Also, I did not write that this was necessarily evidence of positive selection. What I actually indicated was that "a different MC1R variant -- the derived rs8045560 allele, which is associated with light skin pigmentation -- has been observed at significant frequencies among Europeans; particularly in the south and adjacent areas," and that "unexpectedly, however, this allele is also found at high frequencies among the San population in Namibia". This too can be seen in the ALFRED [9]. Soupforone (talk) 17:01, 24 June 2016 (UTC)

WP:SCIRS applies to this article and its sourcing. You cannot insert your own theories (WP:OR) or a novel analysis of theories (WP:SYNTH) here. You need to cite to peer-reviewed materials, and something like a PhD thesis would only be acceptable if it were also approved for peer-reviewed publication (some are) or, occasionally, if it somehow became notorious or newsworthy, not as a "proven fact," but as something of public interest that required us to "teach the controversy" by addressing it. Neither appears to be the case. To overturn an established scientific view requires, essentially, better evidence than this. Montanabw^(talk) 18:35, 24 June 2016 (UTC)

Here is the actual passage, with the associated links:

A different MC1R variant -- the derived rs8045560 allele, which is associated with light skin pigmentation [10] -- has been observed at significant frequencies among Europeans; particularly in the south and adjacent areas. Unexpectedly, however, this allele is also found at high frequencies among the San population in Namibia (58%).[11] Likewise, MC1R alleles have been found in various prehistoric European populations, such as in Motala culture burials dating from the Mesolithic (~8,000 year ago).[12]

None of the above are personal theories. The Portuguese analysis is by Rodrigo Rodenbusch, who is the director of the FEPPS laboratory. The ancient tomb analysis is by Lazaridis. The allele frequencies are also as indicated in the ALFRED. For instance, the San really do have around 58% of the derived rs8045560 allele. The Human Genome Diversity Project indicates as much too [13]. Anyway, it is what it is. At least now it's clear what are the actual frequencies for this allele. Soupforone (talk) 22:16, 24 June 2016 (UTC)

Yes, but you are putting them together in a way that makes it sound like the current scientific consensus is different to what it really is.

- The Portugese PhD actually says "the ancestral allele C of rs8045560 (C>T SNP) is associated with darker skin populations". There is no study (AFAIK) that associates the derived T allele with lighter-skin populations as your suggested text states.

- The ALFRED allele frequencies have no meaning by themselves - there are lots of alleles that peak in European populations that have nothing to do with skin colour. Taken with the misquote of the PhD it implies there is an association where none has been proven. In light of that the mention of San frequencies is meaningless.

- The mention of prehistoric populations is misleading because the rs8045560 allele isn't one of the ones reported in the cited paper. Your phrasing (eg "likewise") makes it sound like it's somehow connected to the first two sentences when it isn't.

The current theory of the wide MC1R variance in Europe is that it was under functional constraint in the tropics, where melanin production is (or was) essential to survival. As people moved north this restriction was removed and mutations which affected melanin were allowed to arise and propagate randomly. MC1R's distribution in modern populations is consistent with random inheritance and perhaps sexual selection in some areas, unlike the SLC's which show very clear signs of positive selection. I think the current wording is a better reflection of this than the changes you propose.

Tobus (talk) 02:15, 25 June 2016 (UTC)

I understand, but if an individual carries the derived T variant of rs8045560, this means that he/she lacks the ancestral C variant of rs8045560 that is associated with darker skin. Ergo, the derived allele is linked with a lighter pigmentation. Please see the HGDP map - the derived allele is highest among European populations [14]. With that said, the Motala bit indicates that "MC1R alleles have been found in various prehistoric European populations, such as in Motala culture burials dating from the Mesolithic (~8,000 year ago)"; it doesn't mention the rs8045560 allele specifically. Perhaps "also" would have been a more preferable sentence connector. Anyway, the claim that "no evidence is known for positive selection of MC1R alleles in Europe" is absolutist. Savage analysed this and found that "Tajima's D statistic suggested the presence of positive selection in individuals from Europe" [15]. Given this, I think at least the phrasing here should be softened to something like "it is uncertain whether there has been positive selection of MC1R alleles among individuals from Europe". Soupforone (talk) 14:42, 25 June 2016 (UTC)

It would be nice if it worked that simply, but biology is far more complicated - I mean, 50% of Danes don't have dark skin do they? I suspect the reason there's no association of rs8045560 with light-skinned populations is that the genes that *do* cause light skin effectively bypasss the effects of MC1R - it doesn't matter if your toaster is set to light, medium or dark if it's not plugged in and the switch is off, nor if you have no bread. That's why we see random-looking frequencies in Europe but consistent near-fixation in Africa - the allele has no effect on already depigmented skin and so just propagates randomly.

Savage's study doesn't show Tajima's D results for each allele but only for the set, and as I said before, gives mixed and borderline significant results - if MC1R was positively selected for in Europeans it wasn't across the board and wasn't very strong. The fact that the populations showing signs of selection are in the Meditteranean makes we wonder if it's not tanning response or olive skin alleles that are being detected, not the depigmentation ones.

Note that the purpose of the sentence you are contesting is to contrast with the previous sentence on East Asia, where MC1R *has* been associated with population-wide depigmentation. Such evidence has not been found in European populations and any changes made to the text would need to reflect this - MC1R isn't the reason that Europeans are "white".

Tobus (talk) 01:19, 26 June 2016 (UTC)

I think you misunderstood me there. Just so it's clear, I'm not claiming that MC1R is the only or even the chief reason why Europeans are fair-skinned. The latter would probably instead be the derived SLC24A5 allele. What I'm saying is that MC1R is one of several pigmentation genes that are intrinsic in the phenotype. Please see for example Sturm and Duffy 2012 (in Europeans MC1R variant alleles are associated with pheomelanic red hair, fair skin and freckling, as well as skin cancer risk [16]). Anyway, point taken about the Tajima analysis. Soupforone (talk) 03:00, 26 June 2016 (UTC)

I come at this from the effects of MC1R in equine coat color genetics, but I think that application is enlightening. Horses that are recessive for this allele are, at base coat level Chestnut (coat) ("red"), akin to blonde or redheaded people (yes, I'm oversimplifying). Horses that have the allele are, at base, Black (horse. Then, to complicate matters, the actions of the Agouti gene on horses suppress the black color to red, other than for point coloration, making such horses bay (horse). Hence, some horses with a bit of red coloring can have this allele, but it is overlaid by another one that make them look "red", though not completely. (Perhaps this is akin to light-skinned people who can tan, I don't know) But, the dominant allele of MC1R in horses has zero to do with the existence of a red coat, if a red horse has MC1R, it is because of additional genes suppressing the black color. I hope this clarifies the point here-- MC1R doesn't "cause" fair skin, though the allele may be present in European populatios. Montanabw^(talk) 21:06, 26 June 2016 (UTC)

As long as other species are being mentioned, in dogs, MC1R has no effect on skin, but prevents deposition of pigment in hair, so a yellow lab or golden retriever are MC1R- but still have black or chocolate skin. (The same applies to the white coyotes of Newfoundland, who are thought to have gotten their MC1R from a golden retriever introgression). 50.37.113.35 (talk) 19:01, 8 July 2016 (UTC)

Citation Needed - Editorial Consensus

Right now there is Citation Needed tag in the lead of this article that has questionable function. Here is the section of policy that defines this issue...

Wikipedia:Manual_of_Style/Lead_section#Citations

Because the lead will usually repeat information that is in the body, editors should balance the desire to avoid redundant citations in the lead with the desire to aid readers in locating sources for challengeable material. Leads are usually written at a greater level of generality than the body, and information in the lead section of non-controversial subjects is less likely to be challenged and less likely to require a source; there is not, however, an exception to citation requirements specific to leads. The necessity for citations in a lead should be determined on a case-by-case basis by editorial consensus. Complex, current, or controversial subjects may require many citations; others, few or none. The presence of citations in the introduction is neither required in every article nor prohibited in any article.

Here is the sentence that is requesting a citation.

MC1R has also been reported to be involved in cancer (independent of skin coloration), developmental processes, and susceptibility to infections and pain.[citation needed]

I completely grasp that this sentence falls under the purview of "challengeable material." However, the last four subsections of the Functions section - which is directly below the lead - contain more details on all these reported effects of variations of the MC1R gene, and there are ample citations on each of those subsections. It seems to be that adding multiple citations to that one sentence in the lead would be highly redundant and 'out of balance'.

For this reason I think the tag should be removed. But because it's something that should have editorial consensus, I felt it was important to open it up to discussion. CleverTitania (talk) 21:34, 2 September 2018 (UTC)

Minor Restructuring Suggestion

If you haven't been following this conversation previously, the section above called Red hair and freckles will give you the backstory details. However because I am now suggesting a restructuring of the page, I am moving this discussion into its own section.

I went to make the changes agreed to above, and realized that the entire last paragraph in the Coloration in Mammals subsection needs to go, for two reasons.

1. As we've determined, the facts in the latter part of that paragraph have no source at all. And the information I was going to replace them with, from the abstract of the study cited, is already in the Pigmentation genetics section of this article.
2. The source in the first part of the paragraph, claiming that 25% of the population has the mutated MC1R gene, is a website that sells at-home MC1R gene testing kits. And the numbers quoted from that website have no further reference on their website I can find - so they could've been invented for marketing purposes. In fact of the three links that are on the webpage in the citation, two are links to this Wikipedia article, and the third is broken. So that is not remotely a reliable source.

I understand why the Coloration of Mammals subsection is under the Functions section, and why someone tried to include information about human coloration in that subsection. But it's basically giving us two separate Pigmentation genetics areas on the page, both of which cover other animals and humans. I feel like the only wise solution is to merge all of that information into one place. But if you move everything in the Pigmentation genetics section into the Coloration of Mammals subsection that will be pretty long for a subsection. So I was trying to think of simple ways to fix this problem, that didn't require a major restructuring of the article.

My solution: We create a section just below the lead, titled something like, "Pigmentation and Coloration Functions." All the information about pigmentation and coloration would go there. Then below that would be a section titled "Additional Receptor Functions," which contains the other subsections currently found in the Functions section. That seems to be the smoothest and most organized way to fix this. But I am of course open to other suggestions.CleverTitania (talk) 22:26, 2 September 2018 (UTC)

@CleverTitania: I think that's a very sensible solution. I've seen something heading structures in other gene/protein pages. T.Shafee(Evo&Evo)^talk 11:21, 14 October 2018 (UTC)

Mutation merge in

Melanocortin 1 receptor Asp294His should probably be merged into this page rather than sitting separately. T.Shafee(Evo&Evo)^talk 11:10, 14 October 2018 (UTC)

--Akrasia25 (talk) 15:45, 27 October 2019 (UTC)

Out of Africa "debunked"

The section entitled "Pigmentation genetics" characterizes the Out of Africa hypothesis for human origination and migration as debunked, whereas neither the Wikipedia article on this topic nor the citation give adequate evidence to this effect, much to contrary, conceding that OOA represents the current scientific consensus, and has remained so despite the ongoing revisions to the details.

Suggestions should be eliminated that the recent African origin of modern humans is not scientific. Epl (talk) 19:31, 24 January 2021 (UTC)