1. Where do Blue Eyes Come From?
In humans, blue eyes are caused by a recessive allele found most frequently in northern European populations. But where did the first blue-eyed person come from?

2. All humans originated in Africa and had dark brown eyes (an adaptation to the strong equatorial sunlight).

3. Occasionally, a person in African is born with naturally blue eyes.
These individuals did NOT inherit the allele for blue eyes; their eyes are blue due to the random mutation of DNA in their eye cells. However, since this mutation is not adaptive in Africa (allows too much light to enter the eye), it is rare.

4. Around 150,000 years ago, some humans left Africa and migrated north to Europe.
As they migrated, the blue-eye mutation continued to occur with the same frequency as before.

5. In their new environment, the blue eye mutation was highly adaptive; it allowed the ancient Europeans to absorb light more efficiently. Over time, the allele became more common in that population. Like allele new alleles, however, blue eyes originated as a genetic mutation.

6. There are three main causes of DNA mutation
There are three main causes of DNA mutation. Mutations can occur during DNA replication, if DNA polymerase fails to catch mistakes when the new DNA strand is assembled.

7. Mutations can also occur if a DNA molecule is exposed to mutagenic chemicals or radiation, which have enough energy to break the covalent bonds in DNA and change the order of nucleotides in the molecule.

8. Finally, mutations can occur during cell division, if chromosomes fail to separate correctly (nondisjunction error).

9. C A A T A T G G A T G U U A U A C C U A
Most mutations are neutral (have no effect on the final protein). This is because several different codons can call for the same amino acid. C A A T A T G G A T
DNA: G U U A U A C C U A
mRNA:
Valine
Tyrosine
Valine
Leucine

10. Mutations that affect more than one nucleotide generally have a more extreme effect on the protein being expressed.

11. There are two types of mutations: gene mutations and chromosomal mutations. Since chromosomes contain many genes, chromosomal mutations tend to be more severe.
Gene mutation
Chromosomal mutation

12. Frameshift gene mutation
There are two types of gene mutations: point and frameshift.
Point Gene Mutation
Frameshift gene mutation

13. G T A T A C G T A T C G A A G G A C C A T A C T G C A T A G C T T C C
A point mutation occurs when DNA polymerase adds the wrong base to a new DNA strand, then fails to catch the error during proofreading. Point mutations are usually neutral (no effect), or one amino acid may be changed. G T A T A C G T A T C G A A G G A C
DNA: C A T A C T G C A T A G C T T C C T G
mRNA: G U A U G A C G U A U C G A A G G A C
Valine
Cysteine
Tyrosine
Valine
Serine
Lysine
Aspartic
Acid

14. Example of a point mutation: Sickle-Cell Anemia
Mutation of the hemoglobin gene. GAG codon changes to GTG; calls for the amino acid valine rather than glutamic acid. The hemoglobin does not get made correctly; oxygen is not carried by blood as well as it should be. Not severe.

15. Frameshift Gene Mutation
Frameshift mutations are more severe; every amino acid following the mutation is affected.
DNA: C A T T G C A T A G C T T C C T G
mRNA: G U A A C G U A U C G A A G G A C
Valine
Tyrosine
Threon.
Tyrosine
Valine
Arginine
Serine
Arginine
Lysine ?
Aspartic
Acid
Frameshift Gene Mutation

16. Example of a frameshift mutation: Cystic Fibrosis
Mutation of the CFTR gene. 3 nucleotides deleted, resulting in the loss of the amino acid phenylalanine from the protein. Ion channel in lung cells doesn’t work properly; fluid not transported out. Thick mucus; severe breathing problems.

17. Chromosomal mutations do not affect individual nucleotides
Chromosomal mutations do not affect individual nucleotides. Rather, they affect the number or structure of chromosomes.
Down Syndrome
Turner Syndrome

18. Normally, humans have 46 chromosomes (23 pairs).
Female (XX)

19. Normally, humans have 46 chromosomes (23 pairs).
Male (XY)

20. Example of a chromosomal mutation: Down syndrome
In Down syndrome, the number of chromosomes is affected (trisomy 21).

21. Instructions for making protein are correct, but there are 3 copies instead of 2. Proteins are over-expressed (esp. in the brain, where excess protein causes neurons get “tangled.”)

22. Example of a chromosomal mutation: Turner syndrome
In Turner syndrome, the structure of chromosomes is affected (a piece of chromosome 23 breaks off).

23. Females with Turner syndrome may not get their period/grow breasts, depending on the size of the missing piece of their sex chromosome.

24. Another Chromosomal Disorder: Trisomy 23 (XXY)

25. Trisomy 23 (XXY) AKA Kleinfelter’s syndrome

26. The majority of mutations are neutral
The majority of mutations are neutral. Sometimes (in the case of genetic diseases) mutations are harmful. However, mutations can also be beneficial.

27. Example of a beneficial mutation: HIV resistance
Caused by a mutation on the CCR5 gene. CCR5 is a membrane protein located on the surface of cells. Without it, the HIV virus cannot attach to cells or inject its DNA.

28. People with this mutation cannot get AIDS, even if the virus enters their body via sexual intercourse. Interestingly, the CCR5 gene mutation was first identified among a group of female prostitutes in Kenya (all related to each other).

29. Example of a beneficial mutation: super strength
Caused by a mutation on the myostatin (MSTN) gene. Myostatin is a messenger protein that inhibits muscle growth. Without it, muscles grow up to twice as large as normal.

30. The MSTN gene mutation can occur in humans as well as other animals
The MSTN gene mutation can occur in humans as well as other animals. The boy below, Liam Hoekstra, is known as “the world’s strongest child.” He is 8 years old.

31. Example of a beneficial mutation that YOU probably have: lactose tolerance
Caused by a mutation on the lactase gene. Lactase is an enzyme that breaks down lactose, allowing us to digest milk and other dairy products.
The lactase gene is regulated by a promoter. The promoter is supposed to disappear after infancy, but in people with this mutation, the promoter remains for life.

32. People with this mutation have the ability to digest milk long past infancy, allowing them to eat a wider range of foods. Not everyone has this mutation; it occurred in Europe around 30,000 years ago. People without it are lactose intolerant.

33. Example of a beneficial mutation: antibiotic resistance
Certain strains of bacteria (termed “MRSA”) have developed a gene mutation which makes them resistant to penicillin.

34. From the point of view of humanity, this mutation is harmful
From the point of view of humanity, this mutation is harmful. But from the point of view of the bacteria, it is beneficial!

35. Mutation is the source of all genetic variation on Earth
Mutation is the source of all genetic variation on Earth. Without mutation, individuals would be genetically identical to each other (clones).

36. The phenotype of a species is the result of beneficial mutations which occurred in the past. Beneficial mutations are called “adaptations.”