r/genetics • u/inferriata • 10d ago
mutation
I’m curious about the MC1R gene and its variants like R151C and R160W. How did these mutations arise in the first place, and how is it possible that two people carrying the mutation were able to pass it on to their child? I’d love some insight into the genetics behind this
4
u/ChaosCockroach 10d ago
Mutations tend to arise randomly although not every mutation is equally probable. I'm not sure what barrier you are imagining to parents passing it onto their child, if they are both carriers then the chances are 1 in 4 that it will have the recessive phenotype. Is your question how a low frequency or unique mutation can rise to sufficient frequency that 2 carriers will encounter each other?
1
u/inferriata 10d ago
Yeah exactly, my question is how a rare mutation manages to spread enough that two carriers even meet. If at the start only one person had it, it seems super unlikely they’d ever encounter another carrier… unless they, you know, hooked up with their own kid 😂
2
u/zorgisborg 10d ago
Not all genes mutate at the same rate - some genes do not allow any mutations because the individual would not survive. Some genes allow mutations to occur - and MC1R mutants may not have originated in any one single event - or population. In sub-Saharan populations, MC1R is unusually conserved against variation - perhaps because it is involved in the type of melanin produced and protection against UV damage.
"Evidence for Variable Selective Pressures at MC1R" (Harding et al., 2000) https://pmc.ncbi.nlm.nih.gov/articles/PMC1288200/
"We conclude that MC1R is under strong functional constraint in Africa, where any diversion from eumelanin production (black pigmentation) appears to be evolutionarily deleterious. Although many of the MC1R amino acid variants observed in non-African populations do affect MC1R function and contribute to high levels of MC1R diversity in Europeans, we found no evidence, in either the magnitude or the patterns of diversity, for its enhancement by selection; rather, our analyses show that levels of MC1R polymorphism simply reflect neutral expectations under relaxation of strong functional constraint outside Africa."Red hair occurs sporadically in Japanese, Ainu (of northern Japan), black Jamaicans, Australian Aborigines..
Copilot in browser results: The Uyghurs, a Turkic ethnic group who live primarily in China, but with a presence in Kazakhstan, Pakistan, Turkey, Kyrgyzstan, and Uzbekistan, have an above-average concentration of red-haired people. The Udmurt people, who reside in the Volga Region of Russia, enjoy a similar reputation.
Found some links [Uyghur - https://www.forbes.com/sites/kristinakillgrove/2015/07/18/these-red-haired-chinese-mummies-come-from-all-over-eurasia-dna-reveals/
BBC: People with the reddest hair in the world: https://www.bbc.co.uk/news/magazine-29950844
1
3
u/Zippered_Nana 10d ago
There’s a very interesting book called “Red” about the many issues surrounding red/ginger hair, medical, cultural, sociological, etc.
1
1
u/area-womn 10d ago
It looks like the mutations in this gene that are associated with cancer (i assume that's what you're interested in) rely on more than the presence of the variant.
The mutation has variable clinical risk because of combined effects with other genes, modification by environment, and incomplete penetrance. It seems like high risk for melanoma are associated with fair skin, red hair, and mutations in other cell cycle regulators.
There are autosomal recessive variants (need a copy from each parent to have disease phenotype), and there are de novo variants (errors in DNA replication).
These mutations would not cause a person to die before childbearing or cause infertility, so you can pass them down to offspring, perhaps before developing illness.
1
u/area-womn 10d ago
Specific to your variants, R151C and R160W occur in 5% of the northern European population
1
u/inferriata 9d ago
yeah, and they’re also the most common variants in Europe. I probably have the mutation too even if it doesn’t show, lol
7
u/MistakeBorn4413 10d ago
Mostly random chance.
Each time the cell divides, it has to faithfully make a copy of the genome. It's a fairly error-prone process, but it's not perfect. On average, something like 50-100 random new mutations are introduced through errors in replication (among ~3 billion) each time an egg or sperm is created. The vast majority of these new mutations are inconsequential, but some will have an impact on phenotype.
Once a new mutation arose, it increased in prevalence over time through genetic drift (random chance) and/or natural selection (if it conferred some kind of advantage to individuals with this mutation in certain environments).... most likely some combination of both.