Mutation and genetic variation

4.2
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

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]).
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.
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.

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.

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 nonfunctional protein.

Mutation can produce new alleles, but new genes are also produced and gene duplication appears to be most important source of new genes.
Gene duplication
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.

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.
Mutation and genetic variation

Mutations are raw material of evolution. No variation means no evolution and mutations are the ultimate source of variation.
4.2
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. [To refresh yourself on basic DNA structure and protein synthesis see any Introductory Biology textbook]

Mutation rates

Applying mutation rates to entire genome gives estimate of approximately 15 mutations/individual/generation.
Where do new genes come from?

4.7
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.
4.3a
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.

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.
4.1a
4 + 4.1d 4.1b .
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.
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.