GOOD? BAD? NO EFFECT? MUTATIONS

When you think of mutations… Does this come to mind? Or this? How about this? Chances are you said…YES! Genetic mutations are not always what we think…

What are Genetic Mutations? Any permanent change to DNA, and sometimes RNA Beneficial mutations can increase variation and lead to adaptation Harmful mutations can cause disorders, deformities, or even death Can occur spontaneously, usually during DNA replication Can occur due to exposure to external factors Chemical mutagens: THC, cigarette smoke, toxins Radiation: UV, X-ray

Most Mutations have NO effect! This because MOST of an organism’s DNA is not active protein encoding DNA, so chances are when and if mutation occurs, it will be in this DNA Also, if you remember many amino acids have codons with a ‘wobble’ base…so if mutation occurs here it doesn’t change the protein or its function.

Body Cell vs Germ Cell Mutation Body Cell mutations are called somatic mutations They affect only that cell’s ability to function They affect any daughter cells resulting from mitosis They cannot be passed to offspring Example: cancers caused by behaviors like smoking, exposure to toxins in herbicides and pesticides Germ Cell mutations are those found in the gametes They are passed on to offspring Are present in every cell’s DNA They affect every cell of the offspring Examples: Genetic disorders, genetic cancers, structural /functional protein errors

Types of Mutations Mutation can be as small as a change to a single base, or as large as loss of an entire chromosome!

Gene or Point Mutations Changes to bases-that result in changes to the protein Examples: Missense SUBSTITUTIONS: 1 base: codes wrong AA Nonsense SUBSTITUTIONS: 1 base: codes STOP

Gene or Point Mutations FRAMESHIFT deletions: lose a base FRAMESHIFT insertions: add a base Both result in a misreading of codons and wrong protein or no protein Frameshifts can occur with the insertion or deletion of two bases as well

Duplications/Tandem Repeats DUPLICATIONS: codons are repeated, so amino acids are duplicated TANDEM REPEATS: repeat of several of the same codon

CHROMOSOMAL MUTATIONS Include loss/moving of sections, or even the entire chromosome Like gene mutations, chromosome mutations include substitutions, deletions, and duplications Unlike genes, these mutations, involve large amounts of DNA and many genes Result in greater, mostly negative phenotypes, most are lethal mutations Other types of chromosome mutations include inversions, translocations and non-disjunctions….let’s take a look at those.

Types of Chromosomal Mutations Deletions: loss of sections of chromosome, may include many genes A B C D E Duplications: sections are duplicated C D B A E E C D B A

Types of Chromosome Mutations Inversions: sections are ‘flipped’, results in the wrong side of the DNA being transcribed=no protein B A C D E Translocation: end of one chromosome is attached to the end of a non homologous chromosome During which event of meiosis are these types of mutations more likely to occur? B A C D E W X Z Y CROSSING-OVER

Non-disjunction Mutations Disjunction refers to the separation of sister chromatids during anaphase of meiosis I and II NON-disjunction refers to the failure of chromatids to separate, as a result…gametes can form with the incorrect number of chromosomes

Non-disjunction Mutations The severity of non-disjunction mutations depends upon whether they occur during meiosis I or meiosis II ALL GAMETES ARE AFFECTED HALF OF THE GAMETES ARE AFFECTED

POINT: MISSENSE SUBSTITUTION AWV SOMATIC: AFFECT ONLY CELLS OF THE ORGANISM GERM CELL: AFFECT OFFSPRING POINT: CHANGES TO BASE OF GENE CHROMOSOME: LOSS OF MANY GENES POINT: MISSENSE SUBSTITUTION SINGLE BASE CHANGES CAN STILL RESULT IN SAME AMINO ACID EVEN IF AN AMINO ACID IS DIFFERENT, PROTEINS ARE SO LARGE USUALLY LITTLE EFFECT AWV 6 CODONS: VALINE-SERINE-ALANINE-GLYCINE-PROLINE-LEUCINE-THREONINE-ARGININE 1 CODON: METHIONINE-TRYPTOPHAN TEF ATC ATA TET HER AT NO, IT MAKES NO SENSE THIS IS A FRAMESHIFT DELETION MUTATION 105 DIVIDED BY 3 = 35 TOTAL AMINO ACIDS IN PROTEIN 84 DIVIDED BY 3 = 28 CORRECT AMINO ACIDS, 7 INCORRECT

SEQUENCE #1 AND #3 ARE THE SAME ILLUSTRATES EVEN WITH DIFFERENT SER LEU ALA THR ARG SER SEQUENCE #1 AND #3 ARE THE SAME ILLUSTRATES EVEN WITH DIFFERENT CODONS THE SAME PROTEIN CAN RESULT SER LEU ALA THR SER SER SER LEU ALA THR ARG SER NORMAL SICKLE CCC GAA GAA AAA CCC GUA GAA AAA PRO GLU-A GLU-A LYS PRO VAL GLU-A LYS POINT SUBSTITUTION: A SINGLE BASE IS CHANGED AND 1 AA CCC GAA GAA UUU PRO GLU-A GLU-A PHE PROBABLY; GLU-A IS IN CORRECT POSITION EVEN THOUGH THERE IS A DIFFERENT POINT MUTATION FURTHER DOWN THE BASE SEQUENCE

DELETION AT B DUPLICATION OF B INVERSION OF B & E TRANSLOCATION OF JKL AND DEF CROSSING-OVER GENE DELETIONS AFFECT A SINGLE PROTEIN CHROMOSOME DELETIONS AFFECT MANY GENES THUS MANY PROTEINS

EACH GAMETE SHOULD HAVE 2 CHROMOSOMES FAILURE OF CHROMOSOMES OR CHROMATIDS TO SEPARATE DURING ANAPHASE I OR II EACH GAMETE SHOULD HAVE 2 CHROMOSOMES “3 BODIES” = TRISOMY

MALE FEMALE 6. MISSING A SEX CHROMOSOME 7. MONOSOMY 8. EXTRA #21 9. TRISOMY 21 DOWN SYNDROME