Mut a tions

 Cells do rarely make mistakes copying their own DNA resulting in a change in the DNA.  Mutation – a change in genetic material (DNA).  There are many types of mutations – we will look at some of them.

Mutations Mutations can be spontaneous or can be caused by chemical or physical factors (mutagens). Examples: cigarette smoke, X-rays, benzene, bromines.

Mutations  Genetic changes (mutations) can occur in either somatic (body) cells or in germ cells (cells that will give rise to gametes).  Somatic cell mutations only affect the cells that are produced by mitosis from the mutant cell. This can be important (e.g. cancer) but does not get passed on to the individual’s offspring.

Mutations  Germ cell mutations are incorporated into gametes (sperm or eggs).  All of the cells of the new organism resulting from the joining together of the mutant gamete with another gamete will have the new genetic composition (mutation).  Germ cell mutations are inherited (passed down to offspring).

Mutations - types  Gene mutations – mutations that produce changes in a single gene.  Point mutations – gene mutations that involve changes in only one (or a few nucleotides).  Substitutions – a different nucleotide  Insertions – an extra nucleotide  Deletions – a missing nucleotide

Effects of * Point Mutations *  Substitutions – usually affect only a single amino acid.  Recall that there is actually some redundancy in the genetic code.  Most amino acids have more than one codon that codes for them.  ex. Proline is coded for by CCU, CCC, CCA and CCG.

Effects of Point Mutations  If the change is in the third base of the codon, there is frequently no change in the amino acid sequence.  This means that if there is no change in the amino acid sequence, there is NO EFFECT on the protein coded for by that gene and NO EFFECT on the organism.

Effects of Point Mutations  If the single change causes a different amino acid to be coded for, ex. CAC (histidine) changed to CAG (glutamine), then this one small change may significantly change the shape or bonding characteristics of the protein.  The protein may no longer work effectively.

One point mutation is all that is takes to cause the sickle cell allele (abnormal hemoglobin protein).

Results of mutations  Can be very harmful (death or disease)  Can be neutral (neither harmful nor good) or not too much different from normal.  Rarely, mutations may prove to be useful to the organism and be passed on to offspring.  All the different alleles present in gene pools are there because of mutations.  This is the raw material on which natural selection acts.

Effects of Point Mutations  Substitutions – usually affect only a single amino acid.  Insertions and deletions are often more dramatic—changing the groupings of the bases. This is called a frameshift mutation.  AGC CA GTC CCG GTT deletion

* Frameshift * mutation example  Thecatatetherat  If read like a ribosome reads it (1 codon, 3 “letters” at a time)  The ‍ cat ate the rat  If the 3rd letter is deleted…  Thecatatetherat  Thcatatetherat  Now the line is read…  Thc ata tet her at ??????  Everything downstream from the mistake is affected.

**Chromosomal Mutations**  Changes in the number or structure of chromosomes.  Larger-scale change than point mutations.

Chromosomal Mutations  Duplication – part of a chromosome is copied and added to the chromosome.

Chromosomal Mutations  Deletion – part of the chromosome (some of its genes) are lost from the chromosome.

Chromosomal Mutations  Inversion – a piece of the chromosome is snipped out and then reattached – only in the reverse direction.

Chromosomal Mutations  Translocation – a piece of one chromosome is attached to a another chromosome.  Often, two non-homologous chromosomes trade pieces with each other.

Chromosomal Mutations  The largest change in the DNA of an organism is a change in the number of chromosomes it has.  One can observe these changes in a karyotype.  A karyotype is a visual representation of the chromosomes of an organism.

Mouse Karyotype

Dog Karyotype

HeLa Karyotype

Meiosis – Begin with one diploid germ cell and produces, after two rounds of division, four haploid gametes.

Errors in meiosis Occasionally, there are errors in meiosis resulting in the wrong number of chromosomes in the gametes. Aneuploid – having an abnormal number of some chromosome.

Errors in meiosis Monosomic – Only one of some homologous pair (too few) Trisomic – Three of some homologue (too many)

Errors in meiosis The primary cause of these irregular chromosome numbers is nondisjunction – the failure of chromosomes to separate correctly in Anaphase I or Anaphase II of meiosis.

The gametes should all have one chromosome for this example (2n = 2, n =1).

* Nondisjunction * in humans The most common observable condition in humans related to nondisjunction is Down Syndrome. This is caused by Trisomy 21(three copies of chromosome 21). With only a couple of other rare exceptions, trisomies of autosomes in humans are not viable. Fertilizations involving monosomic gametes (one too few) do not survive.

Down Syndrome Down syndrome affects approximately one out of every 700 children born in the U.S. All body cells have 47 chromosomes (3 chromosome 21's) Down syndrome causes characteristic facial features, short stature, and developmental delays. Increased incidence of leukemia, Alzheimer's Decreased rates of high blood pressure, hardening of the arteries, many types of solid tumors.

Trisomy 21 (Down Syndrome) - female

Trisomy 21 (Down Syndrome) - male

Chromosomal mutations Plants have a much simpler developmental plan than do animals. Plants are more immune to the genetic disruption caused by many types of mutations.

Chromosomal mutations One common type of chromosomal mutation in plants is polyploidy. Polyploidy is the multiplication of entire sets of chromosomes (four, six, eight sets of chromosomes instead of the usual two (diploid) Polyploids are often larger and more vigorous than their diploid relatives (ancestors).

Allopolyploid

Effects of Point Mutations  Insertions and deletions are often more dramatic—changing the groups the bases are read in. This is called a frameshift mutation.  AGC TCA GTC CCG GTT

Effects of Point Mutations  frameshift mutation.  AGC CA GTC CCG GTT  Now the codons are read: AGC CAG TCC CGG TT? etc.  Every codon past the frameshift mutation is affected (changed). The protein will probably be altered so much that it no longer functions. deletion

Chromosomal Mutations Deletion Duplication Inversion