Genes linked to hair loss and hairiness

Studying mammals that have lost hair over evolutionary time reveals the genes linked to how hair works...
01 March 2023

Interview with 

Nathan Clark, University of Utah




To a subject that goes over most people’s heads, but literally, rather than in an intellectual way: I’m talking about hair, and why we have it, or not; where we have it, and what sort of hair we have across different parts of the body. It’s so consistent that it must be genetically determined. But, hitherto, only a relatively small number of genes have been linked to hairiness. Now, the University of Utah’s Nathan Clark has hit on a method that’s found many more. As he explains to Chris Smith, his team reasoned that many different mammalian species have independently evolved to lose their hair. So if you look for genes that are consistently linked to this happening, it’s highly likely they’ve got a role to play in how hair works…

Nathan - We were looking at all of mammals and one of the most special traits that mammals shares that we have hair, right? But if you look at the diversity of mammals, you quickly realise there are many species that have actually lost most of that hair and they are more closely related to other species that continue to have hair. So we were interested in understanding which genes are responsible for mammals losing hair. And so we asked ourselves, did those species lose their hair through the same type of genetic mechanism? Did we all lose our hair because of changes in the same genes?

Chris - I suppose the subtlety here that one must appreciate is that when you look across the animal kingdom and you find these animals that don't have hair, they have hairier ancestors. So it's not like they're all related from one hair free ancestor, they've all independently lost hair across evolutionary time.

Nathan - Yeah. And, and what allows us to study those species altogether is the fact that us mammals, we share a large proportion of our genes. And so when we produce hair, it's through action of the same genes. So similarly, when species lose their hair, it could also be through the changes to those specific genes as well.

Chris - So if we can find what genes have been mutated to make non-hirsute humans <laugh>, we can solve baldness?

Nathan - Well, perhaps. That that could help us find gene regions to pay attention to if we want to try to start restimulating hair growth. But I have to say that was not our goal in this paper.

Chris - Indeed. But how did you do it?

Nathan - For that I must give a lot of credit to someone. I work with Dr. Amanda Kowalczyk, who came up with this method to study the genomes of these species that have hair and that don't, and she found a way to understand which gene regions are changing more rapidly or they're mutating more rapidly in the hairless species compared to the ones who maintain a full coat of body hair. And when she did that, independently across these different hairless species like the elephants and the rhinoceros and the dolphins what quickly rose to the top were a set of genes called keratins, which we already know are important for the formation of hair. Something that was exciting to come out of that is that Dr. Kowalczyk found there were other genes that we don't know very much about at all, that were also very high on that list. So that immediately suggest to us that those genes are also responsible for the creation of hair.

Chris - When you say "genes that are changing very rapidly," what does that mean?

Nathan - So normally when a gene is important to an organism, over long periods of time, the gene will resist change. So over time those genes appear to change not at all, or at least very slowly because they're so important. However, when a species no longer needs a particular function like hair, those genes will be allowed to deteriorate. There will no longer be kind of mechanisms to remove those mutations.

Chris - How did you do this then? Did you consider many, many species in parallel and look at those same genes and ask which ones are changing a lot and then realise that they are the hairy ones or rather the non hairy ones?

Nathan - Exactly. We group the species together into the hairy ones and the reduced hair or hairless species. And we have ways of kind of measuring the rate of change, you know, the numbers of changes that occur in a particular gene, say per million years. And we were able to do just a simple statistical test to ask whether any particular gene was evolving more rapidly in the hairless species compared to the hairy ones. And that produced this list that we studied.

Chris - And how many genes have you now got that are linked in some way to being hairy or not?

Nathan - Well, it depends on where you draw the threshold for confidence, but I would say, you know, around 100 genes.

Chris - When you look at those genes and you look at what we already knew or suspected was involved in hairiness or being hairless, how many of them are new hits?

Nathan - I think new hits we would have around 20 to 30. But those we need to still follow up and validate or kind of prove that they really are contributing to hairlessness.

Chris - So at the moment you can link them but you don't know what they do. Is that a reasonable summary?

Nathan - That's a perfect summary. For right now, this is the first step in a process of discovery where we can exploit this interesting difference, but evolutionarily between hairless and hairy species. And so the remaining steps are to experimentally go and determine and validate that.

Chris - What do they look like they might do? You must have looked at them and got some kind of initial instinctive reaction to what they look like they might be doing. You mentioned the keratins, obviously they're the hairy proteins, so it's, it's obvious that some of those may change, but what about the others?

Nathan - There's a particular group that scored very highly. We found about four micro RNA genes, which are genes that don't encode instructions to make a protein, but instead they kind of bind to and interact with messages within the nucleus in the cell to turn genes down to kind of change how much protein is being made by other genes. So you can think of them as kind of master dials or regulators and switches. Some of these nothing was known about them whatsoever. So it seems like they're kind of, some of these new genes are master controllers that act in skin and hair development.

Chris - It sort of strikes me that what you now have is almost a shopping list of places to go and look at that have some kind of intriguing, but as yet undetermined link to how hairy a body part is. So this is quite exciting. You've now got plenty of work and plenty of avenues to pursue.

Nathan - For sure. We've definitely been already contacting a couple of groups that study kind of hair follicle and hair formation within models like mice. And more and more people keep suggesting we go talk to companies that are interested in hair stimulation and hair growth and you know, perhaps that's an avenue like a partnership we could find later.

Chris - But flipping that round, there are some agents - some drugs - which, as a side effect, do promote hirsutism. So perhaps what you could do is to say, "well, we'll look at those things and see if they do have some kind of impact on some of these genes."

Nathan - That's a great idea. Yeah. Looking for any kinds of perturbations we can make and experimentally find changes.


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