Steven Crane Compiled Section Handouts. Human Behavioral Biology 2012

Phenylketonuria (PKU)

And two examples related to testosterone?

1. If your T receptors are mutated and don't function, you are genetically XY male but have female appearance because your body doesn't respond to the presence of T. This is testicular feminization syndrome.

2. Enzyme that makes T is mutated in early life, but doesn't hold back T production at puberty in populations in New Guinea and Dominican republic. Guevedoces: what are thought to be "girls" (but are actually XY) develop male secondary sexual characteristics around puberty when T kicks in.

And an example related to anxiety?

1. The benzodiazepine receptors come in different versions based on subtle mutations.

2. The better the receptor binds BDZs, the less anxious the individual will be. If they're very poor BDZ binders, the individual will have an anxiety disorder.

How can micro mutations tell you about evolutionary ancestry trees?

1. 
   We share "the gene" for many proteins with distantly related species (a significant percentage of our genes are shared with bananas, for example).
   
2. 
   But as species evolve and diverge, differences accumulate in our genes so that the proteins of very distantly related species have many differences between them while the same proteins in very closely-related species have very few differences between them.
   

How do you know if a protein has undergone positive selection or negative selection?

1. 
   Take a protein product that is shared between species, like a serotonin receptor shared between dogs and humans.
   
2. 
   Look at the DNA sequence that codes for that protein. Just by random chance we expect, say, 1/3 of the mutations (differences) between those two DNA stretches to actually code for a different AA (amino acids), resulting in a slightly different protein.
   
3. 
   However, if 3/4 of the mutations coded for different AAs, this gene has undergone positive selection and the differences that have accumulated were the result of selective forces over time selecting for a new and better version of that gene.
   
4. 
   If say 1/8 of the mutations coded for different AAs (that is, more of the mutations were neutral than you'd expect by chance), then that gene has undergone negative selection/stabilizing selection, meaning that it is very conserved among species because slight changes have been selected against.
   

• 
  If that's still confusing, here's another explanation from last year:
  
  • 
    You start off with a gene in an organism at time T₁.
    
  • 
    After a long evolutionary time period during which the gene has undergone numerous mutations, you come back and re-examine the gene, which is no longer identical to its original form.
    
  • 
    You're comparing the newer version of the gene at time T₂ to the original gene at time T₁ and looking at the mutations that have happened.
    
  • 
    Based on the type of mutations (silent/neutral or consequential) that you see, you can know whether this gene has faced selective pressures or not, and if so, what type of selective pressure.
    
    • 
      If nothing interesting has happened and those genes have not undergone any particular selection pressures, you'd expect 1/3 of the mutations to be consequential (due to the mathematics of the DNA-amino acid link).
      
    • 
      But if significantly more than 1/3 (like 90%) of the mutations are consequential, the gene has undergone positive selection because having so many more consequential mutations (ones that actually make a difference in the protein formed) than would be expected by chance means that, in order for this gene to have evolved this way and exist in its present form, that large number of consequential mutations must have been selected for.
      
    • 
      And if significantly fewer than 1/3 (like 5%) of the mutations are consequential, the gene has undergone stabilizing/negative selection (pressures to keep the gene exactly how it functioned originally). This is because when consequential mutations happened along the line from T₁ to T₂, those changes were selected against and the original genetic sequence is highly conserved.
      

What is the 95% of DNA that doesn't code for proteins?

• 
  Promoters, repressors, and "junk DNA" which we don't know much about
  
• 
  The longer the genome in a species, the greater percentage of genes tat code for TFs
  

How do you know when to express certain genes?

1.