Angelina Jolie, Evolution and Pleiotropy

Angelina_jolie_by_philipp_von_ostau

Angelina Jolie (2010)
Credit: Philipp von Ostau

Angelina Jolie recently revealed she underwent a double mastectomy; a prophylactic measure to combat the risk of breast cancer associated with BRCA1 gene she carries. Like many other ‘disease’ genes BRCA1 and BRCA2 show evidence of positive selection, suggesting a fitness advantage. To understand how BRCA provides an evolutionary advantage we have to look at the other side of the BRCA coin and introduce the concepts of evolutionary tradeoffs and antagonistic pleiotropy.

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Credit: Wikipedia

An evolutionary tradeoff is just what it sounds like; the gain or enhancement of one trait which causes the loss or suppression of another trait.  At the gross level the concept is easy to grasp; a specialized sprinter must forsake stamina for speed. Perhaps the classic example is sickle-cell which provides resistance and lowers infant mortality from malaria in its heterozygous state but in the homozygous state produces disease and increases mortality. These tradeoffs are observed in all species, even in viruses; a ‘generalist’ virus experiences reduced replication in favor of wide host range while a ‘specialist’ replicates better but with a narrow range of hosts (Nikolin 2012).[N.B. the word “trade” should not be read in any way that suggests purpose or intention]

Pleiotropy occurs when a locus affects more than one phenotype; antagonistic pleiotropy refers to a gene with both, positive and harmful effects. Pleiotropy is also one good reason – there are many – why Myriad’s patent on human genes should be rejected. (Rosenfeld 2013).

BRCA is typically referred to as a cancer gene, but it’s more than that, it is also a ‘fertility’ gene (Smith 2012). In this case, BRCA is associated with increased reproductive potential. The tradeoff is that it comes with the price of increased post-reproductive mortality. Using historical data from the Utah Population Database, Smith et al found that BRCA1/2 carriers had more children, shorter interbirth interval and end child-bearing at a later age.

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Women with BRCA1/2 mutation have more children than control groupK. R. Smith et al

BRCA1/2 positive women have last child at a later age

BRCA1/2 positive women have last child at a later age.
K. R. Smith et al

It’s evolutionary economics; an improvement in fitness during reproductive years is valuable and more than compensates (evolutionarily speaking) for the cost of increased mortality during post-reproductive period. That’s why BRCA1/2 shows signs of positive selection. But of course BRCA is not unique; many other disease genes are maintained in the population due to the effects of antagonistic pleiotropy and this pattern of early-benefit/ post-reproductive mortality.

Genetic diseases with antagonistic pleiotropic effects. Nikolin VM

Genetic diseases with antagonistic pleiotropic effects.
Nikolin VM

Genetic diseases with putative antagonistic pleiotropic effects. Nikolin VM

Genetic diseases with putative antagonistic pleiotropic effects.
Nikolin VM

Just like us, dogs carry the genetic legacy of life history tradeoffs and are subject to many of the same diseases, in fact, Smith suggests antagonistic pleiotropy may be far more widespread than we realize. Dogs carry two other burdens not (typically) observed in human populations; inbreeding and strong artificial selection. Too often, these choices result in exaggerated disease risk. A few examples:

  • Scottish Terriers 20X higher incidence of bladder cancer
  • Fox Terrier 22X for tetralogy of Fallot
  • Boxer 25X for atrial defect
  • Bulldog 13 fold for pulmonic stenosis

In the case of purebred dogs, breed-type (or behavior) can be considered a fitness advantage because, just like under natural conditions, individuals with the desirable trait get to reproduce. We know that most genes have multiple functions, this means very few traits travel alone. In the process of selecting for a particular trait, breeders unwittingly select for genetic diseases. Pleiotropy is not something that is widely talked or written about among breeders. It should be.

“evolutionary insights can enhance our ability to understand,diagnose and heal.” –           SC Stearns, Evolutionary medicine: its scope, interest and potential

Related Links

REFERENCES

Nikolin VM, Osterrieder K, von Messling V, Hofer H, Anderson D, Dubovi E, Brunner E, & East ML (2012). Antagonistic pleiotropy and fitness trade-offs reveal specialist and generalist traits in strains of canine distemper virus. PloS one, 7 (12) PMID: 23239996

Rosenfeld J & Mason CE (2013). Pervasive sequence patents cover the entire human genome., Genome medicine, PMID: 

Smith K., Hanson H., Mineau G., & Buys S. (2011). Effects of BRCA1 and BRCA2 mutations on female fertility Proceedings of the Royal Society B: Biological Sciences, 279 (1732), 1389-1395 DOI: 10.1098/rspb.2011.1697

 

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7 thoughts on “Angelina Jolie, Evolution and Pleiotropy

    • Once an organism is no longer reproducing it is irrelevant to evolution so there is very pressure against the disease.

      Men experience a similar tradeoff with androgen receptor that results in prostate enlargement as they get older.

  1. I work in the breast cancer field (social work, not medical), and have never once heard of the “other” effects of BRCA1. Makes all the sense in the world that there would be a reason it is sticking around. Thank you!

  2. Reblogged this on and commented:
    This post also fits nicely with the previously posted link about health testing. Read it.

  3. “a specialized sprinter must forsake speed for endurance.”

    Shouldn’t it be the other way round?

Comments are closed.