The document discusses mutations as the primary source of genetic variation essential for evolution, explaining how mutations occur at the DNA level, including types like point mutations and frameshift mutations. It outlines mutation rates in different organisms, emphasizing that gene duplication is a significant source of new genes, leading to the emergence of the globin gene family. The document also highlights the consequences of mutations and gene duplication on protein function and expression during development.

1. Mutation and genetic variation
• Mutations are raw material of evolution.
• No variation means no evolution and mutations are the ultimate
source of variation.

2. Where do new alleles come from?
• DNA made up of sequence of nucleotides. Each nucleotide includes a
sugar, phosphate and one of four possible nitrogenous bases
(adenine and guanine [both purines], and thymine and cytosine [both
pyrimidines]).

3. 4.1a

4. 4
.
4.1b + 4.1d

5. Where do new alleles come from?
• The opposite strands of the DNA molecule are complementary
because the strands are held together by bonds between the
opposing bases and adenine bonds only with thymine and cytosine
only with guanine.
• Thus, knowing the sequence on one strand enables one to construct
the sequence on the other strand.

6. 4.2

7. Where do new alleles come from?
•Sequence of bases in DNA codes for protein structure
as each three base sequence codes for one amino acid
in the protein chain.

8. 4.3a

9. Where do new alleles come from?
•When DNA is synthesized, an enzyme called DNA
polymerase reads one strand of DNA molecule and
constructs a complementary strand.
•If DNA polymerase makes a mistake and it is not
repaired, a mutation has occurred.

10. 4.2

11. Types of mutations
•A mistake that changes one base on a DNA molecule
is called a point mutation.
•Two forms:
• Transition: one pyrimidine (T or C) substituted for the
other pyrimidine or one purine substituted for the other
purine (A or G).
• Transversion: purine substituted for pyrimidine or vice
versa

12. Fig 4.4

13. Types of mutations
•Transitions more common than transversions.
Perhaps because transitions cause less disruption
to the DNA molecule and so are less likely to be
noticed by DNA repair molecules.

14. Types of mutations
•Not all mutations cause a change in amino acid
coded for. These are called silent mutations.
•Mutations that do cause a change in amino acid
are called replacement mutations.

16. Types of mutations
•Another type of mutation occurs when bases are
inserted or deleted from the DNA molecule.
•This causes a change in how the whole DNA
strand is read (a frame shift mutation) and
produces a non-functional protein.

17. Mutation rates
•Most data on mutations comes from analysis of
loss-of-function mutations.
•Loss-of-function mutations cause gene to
produce a non-working protein.
•Examples of loss-of-function mutations include:
insertions and deletions, mutation to a stop codon
and insertion of jumping genes.

19. Mutation rates
•Some mutations cause readily identified
phenotypic changes.
•E.g. Achrondoplastic dwarfism is a dominant
disorder. An Achrondoplastic individual’s
condition must be the result of a mutation, if his
parents do not have the condition.

20. Mutation rates
•Human estimate is 1.6 mutations/genome/generation.
• In Drosophila rate is only 0.14 m/g/g, but when
corrected for number of cell divisions needed to
produce sperm (400 in humans 25 in Drosophila)
mutation rates per cell division are very similar.

21. Mutation rates
•These rates are underestimates as they are based
on loss-of-function mutations.
•Direct estimate of number of mutations of all
kinds made for roundworm Caenorhabditis
elegans by sequencing mitochondrial DNA.

22. Mutation rates
•Roundworms can self-fertilize so researchers tracked
74 family lines derived from one female and followed
each for 214 generations.
•At end sequenced 771,672 base pairs of mitochondrial
DNA. Found 26 mutations giving rate of 1.6X10-7
mutations per site per generation. Ten mutations were
insertion/deletions and 16 substitutions.

23. Mutation rates
•Applying mutation rates to entire genome gives
estimate of approximately 15
mutations/individual/generation.

24. Where do new genes come from?
•Mutation can produce new alleles, but new genes are
also produced and gene duplication appears to be most
important source of new genes.

25. Gene duplication
•Duplication results from unequal crossing over when
chromosomes align incorrectly during meiosis.
•Result is a chromosome with an extra section of DNA
that contains duplicated genes

26. 4.7

27. Gene duplication
•Extra sections of DNA are duplicates and can
accumulate mutations without being selected against
because the other copies of the gene produce normal
proteins.
•Gene may completely change over time so gene
duplication creates new possibilities for gene function.

28. Globin genes
•Human globin genes are examples of products of gene
duplication.
•Globin gene family contains two major gene clusters
(alpha and beta) that code for the protein subunits of
hemoglobin.

29. Globin genes
•Hemoglobin (the oxygen-carrying molecule in red
corpuscles) consists of an iron-binding heme group
and four surrounding protein chains (two coded for by
genes in the Alpha cluster and two in the Beta cluster).

30. Globin genes
•Ancestral globin gene duplicated and diverged into
alpha and beta ancestral genes about 450-500 mya.
•Later transposed to different chromosomes and
followed by further subsequent duplications and
mutations.

31. From Campbell and Reese Biology 7th
ed.

32. Globin genes
•Lengths and positions of exons and introns in the
globin genes are very similar. Very unlikely such
similarities could be due to chance.

33. 4.9
Exons (blue), introns (white), number in box is number of nucleotides.

34. Globin genes
•Different genes in alpha and beta families are
expressed at different times in development.
•For example, in very young human fetus, zeta (from
alpha cluster) and epsilon (from beta cluster) chains
are present initially then replaced. Similarly G-gamma
and A-gamma chains present in older fetuses are
replaced by beta chains after birth.