Why do you have blue eyes?

By Razib Khan | September 22, 2007 4:30 pm

Well, you may not have blue eyes, but many people do. The post below suggests that there is still a lot of confusion on how eye color is inherited, but now in 2007 we are coming close to clearing up many issues. A paper which came out early this year, A Three-Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation (Open Access), suggests that about 3/4 of the eye color variation in Europeans (from pale blue to dark brown) can be explained by polymorphism around the OCA2 gene. In other words, eye color comes close to being a monogenic Mendelian trait when it comes to inheritance, but not quite.

The diagram below is probably close to what you learned in high school:

Standard Model Brown heterozygote parent
Blue Brown
Brown heterozygote parent Blue Blue Blue
(Blue phenotype)
Blue Brown
(Brown phenotype)
Brown Blue Brown
(Brown phenotype)
Brown Brown
(Brown phenotype)

In this model the expression of blue eyes is recessive, you need two copies. Heterozygotes, those who carry one copy of each allele, express brown eyes but can have blue eyed offspring. Blue eyed people can only have blue eyed offspring because they have to be homozygotes, carry two copies. A physiological explanation also offers itself up in this case, the blue eye allele is simply a copy which has lost function and results in the lack of production of melanin in the iris. The brown eye allele on the other hand functions normally. Even if only one copy is functioning to produce melanin, that is enough in terms of dosage to produce a brown coloration. Only with two copies which are non-functioning is there a total loss of melanin in the iris.

Reality is more complex. The diagram below is adapted from the paper referenced above. I’ve limited the data to those where the number of individuals in their sample was greater than 10, and those combinations where a proportion of individuals expressed blue eyes. For ease of inspection I’ve continued to color code the genetic variation. Instead of a single clearly defined gene with two alleles, that is, two genetic variants on a well defined physical location, the diagram below illustrates the combinations of two haplotypes, termed diplotypes. This is important because there is possibly no one blue eye gene responsible for all the variation, rather, a host of tightly linked loci may operate as a sort of genetic network. In any case, I have colored the haplotypes so as to show their preponderant average effect.

Adapted from Table 5 of A Three-Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation
Diplotype N Blue/Gray Green/Hazel Brown
Blue 1 / Blue 1 1,772 62.5% 28.0% 9.5%
Blue 1 / Brown 4 138 47.1% 20.3% 32.6%
Blue 1 / Brown 3 154 27.9% 22.1% 50.0%
Blue 1 / Brown 3 154 27.9% 22.1% 50.0%
Brown 3 / Brown 4 12 25.0% 8.3% 66.7%
Brown 2 / Brown 3 29 20.7% 31.0% 48.3%
Blue 1 / Brown 2 364 17.6% 38.5% 44.0%
Blue 1 / Brown 8 253 7.9% 23.3% 68.8%
Brown 2 / Brown 4 18 5.6% 11.1% 83.%
Brown 8 / Brown 8 22 4.5% 0% 95.5%

As you can see there is a strong statistical trend, but the relationship between genetic variation and phenotypic variation is not deterministic. The authors of the paper state, “These data are consistent with the…haplotype 1 [Blue 1] acting as a highly penetrant recessive blue-eye-color allele.” Highly penetrant basically means “a lot of the time, but not always.” As the lower rows illustrate even alleles which are predominantly predictive of brown eyes can together result in offspring with blue eyes! Conversely, a minority of homozygotes for the most powerful predictor of blue eyes still express brown eyes. What’s going on here?

Please note that I said that 3/4 of the eye color variation could be explained by variation around OCA2, that still leaves room for genes of smaller effect to round out the balance. The sample space of the genome is enormous, and one could easily imagine a large number of low frequency alleles at other loci besides OCA2 contributing to loss of function, or gain of function. Reading the paper closely the molecular-physiological nature of OCA2‘s modulation of the expression of this trait doesn’t seem fully elucidated. There are many ways to alter regulatory pathways, so it should not surprise that other genes could account for the remaining 1/4 of the variation. Some scientists would assert that the whole concept of penetrance is a band-aid which exists to mask the reality that a fully understanding of the polygenic nature of a trait has not been achieved.

Note: What I have labeled Blue 1 is extant at around a frequency of 80% in northwest Europe. It seems to have been subject to powerful selection within the last 10,000 years, and is associated with the third longest haplotype within the European HapMap sample.

CATEGORIZED UNDER: Genetics
  • http://interrogatingnature.blogspot.com Chris Harrison

    Why do you have blue eyes?
    Coz i’m part of the chosen race, of course.

  • http://scienceblogs.com/gnxp razib

    dude, you’re a ginger….

  • http://endogenousretrovirus.blogspot.com/ ERV

    … They really did a paper on this?
    How do they operationally define “blue”? Or differentiate “blue” vs “green” vs “blue-green” vs “blue-grey” vs “blue-green-grey”?
    ??

  • http://scienceblogs.com/gnxp razib

    How do they operationally define “blue”? Or differentiate “blue” vs “green” vs “blue-green” vs “blue-grey” vs “blue-green-grey”?
    ??

    well, it’s open access (i assume you could access it institutionally anyway). you can, you know, read it.

  • wrpd

    I am confused. Both my parents had blue eyes. All four of my siblings have blue eyes. But each of them has a different shade of blue. My eyes are sort of bluish-grayish-green. My wife had brown eyes. Our two sons both have blue eyes. My only conclusion is my wife is not the real mother of my sons.

  • http://scienceblogs.com/gnxp razib

    wrpd, reading is good for you. for example, i stated above: As you can see there is a strong statistical trend, but the relationship between genetic variation and phenotypic variation is not deterministic. so why are you confused?

  • Caledonian

    My wife had brown eyes. Our two sons both have blue eyes. My only conclusion is my wife is not the real mother of my sons.

    Why would you reach that conclusion? Even within the old, inaccurate Mendelian model of eye color inheritance, your wife could easily have one dominant brown and one recessive blue gene. The chances of both your sons having blue eyes would then be 1/4.

  • http://endogenousretrovirus.blogspot.com/ ERV

    well, it’s open access (i assume you could access it institutionally anyway). you can, you know, read it.

    Pffff. Cheater. :P

  • VJB

    My wife (blue-eyed) is a bit of fiend about this, believing in the wonderful-ness of blue eyes. I am brown-eyed (my mother had blue) so true to Mendel just one of our two sons has the sapphire orbs. It’s good to see that there is a bit more complication, and also it may be notes that the optical industry can do plausible color contacts. For those to whom it matters a whit.

  • http://akinokure.blogspot.com agnostic

    Finally we historically marginalized hazel-green folks get mentioned! You wouldn’t believe how traumatic it has been growing up in a society where all the “standard textbooks” of what “scientists know” only privilege the narrative of blue and brown eyes.

  • http://www.mythusmageopines.com/wp Alan Kellogg

    WRPD,
    You’ve got two Loki Points so far. Think you’ll pick up more?

  • wrpd

    Sorry, what’s a Loki point?

  • wrpd

    Oooooops. I just found Loki Points using the Googles.
    I was present at the births of both my sons and I am still wondering how the switch was done.

  • Obdulantist

    Finally we historically marginalized hazel-green folks get mentioned! You wouldn’t believe how traumatic it has been growing up in a society where all the “standard textbooks” of what “scientists know” only privilege the narrative of blue and brown eyes.
    Add me to the list of oppressed true hazel-greens. Mine are split colours, green on the outside and brown on the inside. Two of my three siblings are the same. One parent is pale blue, one brown.

  • http://akinokure.blogspot.com agnostic

    My coloring is the same way! Now that I don’t feel like a besieged minority, I can at last develop the confidence necessary to succeed in society.
    What’s your take on our oppression, btw? Are the blues and browns simply envious of those with exotic combinations that change depending on the lighting? Or is it just another instance of the hegemony of binariality in our intellectual culture?

  • pconroy

    Obdulantist, agnostic,
    Ditto here. I have some brown on the inside, then mostly green, with a rim of blue – so I generally call them hazel.
    My Dad has very blue eyes, as had 6 of his 7 siblings, with 1 dark brown eyed.
    My Mom has light brown eyes, with 1 dark brown eyed and 3 blue eyes siblings.
    I have 2 siblings with light brown eyes, 2 blue eyed and 1 dark brown eyed.

  • Sandgroper

    Another oppressed hazel here. Yay us!
    My mother has dark brown eyes and my father had very pale blue eyes.
    My wife’s eyes are medium brown. Our daughter’s eyes are very dark brown but are so dark that in most lighting they look black – how interesting is that?

  • Obdulantist

    Are the blues and browns simply envious of those with exotic combinations that change depending on the lighting?
    Yup. We’re much prettier to look at. He he.

  • Marc

    Don’t start with this oppression of the green-eyed nonsense. My mom and sister both had green eyes. They used to harp on me endlessly when I was a child, favorably comparing their “forest green” eyes to my “dogshit brown” ones. I’m not kidding. I was about eight.
    You people are vicious.

  • Sandgroper

    In such situations a suitable reciprocal epithet would be “duckshit”.

  • Sandgroper

    But to return (?) to the subject of the paper, the only person in my family to be diagnosed with skin cancer was my red haired, blue eyed father. He never got melanoma, though. I worked with a young guy (early 20s) in Oz who got it, also a blue eyed redhead, and he was dead within 3 weeks of diagnosis. The melanoma devil works fast.

  • Carlos Chavez

    can a mother with brown eyes and a father with blue eyes have a child with green eyes?

  • http://www.scienceblogs.com/gnxp razib

    yes.

  • curious gramma

    can two brown eyed parents have a bue eyed child?

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Gene Expression

This blog is about evolution, genetics, genomics and their interstices. Please beware that comments are aggressively moderated. Uncivil or churlish comments will likely get you banned immediately, so make any contribution count!

About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at http://www.razib.com

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