Genetics and Evolution Exam 1

Characteristics of Genetic Material

1. must contain complex information

2. must replicate faithfully

3. must have the capacity to vary.'

4. must encode the phenotype

Structure of DNA

Primary: nucleotide structure and joining (A,C,T,G)

Secondary: stable 3-dimensional configuration (helical phosphodiester structure; major/minor grooves)

Tertiary: supercoiling into chromosomes

Prokaryotes vs. Eukaryotes

Prokaryotes: less base pairs, very short DNA, circular tertiary structure

Eukaryote: much longer base pairs, highly coiled and condensed chromosomes

Chromosomes

storage for DNA

central to inheritance patterns

Chromatin

DNA + Histones

Histones

protein found in eukaryotes that associates with DNA to form chromosomes

Why do chromosomes have to be packed tightly?

Eukaryotic DNA is so long (2 meters in each cell)

Genome

complete set of DNA within an organism

• all of your chromosomes together

Genomics

study of many genes or whole genomes at once

Single Locus Genetics vs. Genomics

Single Gene vs. Many Genes/Genome

What is the genome made of?

• genes

  • exons and introns

• regulatory regions

  • transcription factors

  • gene expression control

• “Junk” DNA

  • ??

What percent of the human genome codes for proteins?

1.5% ; 20,000 genes

Importance of Junk DNA

contains many elements critical for gene expression

Transposable Elements

portion of Junk DNA that actually participates in gene expression processes

• discovered by Barbara McClintock

Human Chromosomes

23 pairs

• 22 autosome pairs (both copies are the same)

• 1 pair of sex chromosomes

  • XX/XY

  • not the same in every organism

What does it mean when its said that pairs of chromosomes are “homologous”?

Pairs of chromosomes are similar with each one coming from each parent

Karyotype

physical examination of the chromosomal structure of an individual

Ploidy

the number of copies of the genetic code

• n= number of genome copies

Diploid

2n

• almost every in the human body

Haploid

1n

• gametes/sex cells

Meiosis

turns 1 diploid (2n) cell into 4 haploid (1n) cells

Central Dogma

DNA → RNA → Protein

Genotype

complete genetic makeup of an organism

• “what is in the book/coded”

Phenotype

set of observable traits in an organism

• “what you see”

• also difference in the amount of proteins

• determined by multiple genes

Is every person unique because they have different genes?

False!

Everyone has the same genes but different alleles

Characteristics of Genes

a segment of DNA that codes for something specific

• mostly proteins

• ALWAYS codes for a phenotype

Allele

one of a number of variations of a gene

• one gene with multiple variations

one of two or more alternative versions or variations of the same gene, found at the same specific location

ex: a diploid individual has 2 alleles (copies) of each gene

Locus

physical location of a gene on chromosome

plural = loci

What are the three different types of chromosome mutations?

1. Rearrangements (leads to same ploidy)

2. Aneuploidy (one chromosome has extra pair)

3. Polyploidy (all chromosomes have an extra pair)

Polyploidy

duplication of the entire chromosomal set

• Triploid- 3N

• tetraploid- 4N

Real-Life Examples of Polyploidy

• many foods are polyploid

  • removes seeds to make sterile

  • increases yield of edible portion

Aneuploidy (Trisomy)

when a single chromosome duplicates

Trisomy 21

Down’s Syndrome

• extra copy of chromosome 21

• most commonly diagnosed chromosomal mutation

Are parents carriers of aneuploidy?

No. Aneuploidy is caused by errors in meiosis

What are the 4 types of chromosomal rearrangements?

• duplication

• deletion

• inversion

• translocation

Chromosomal Duplication

when a section of the chromosome is duplicated

• the duplicated chromosome has to loop out to maintain alignment of the DNA sequences

What are the consequences of chromosomal duplication?

• Imbalances in gene product

• overexpression of genes due to gene dosage (extra copies of genes)

ex: relative dosage of pigment can be changed

Chromosomal Deletion

loss of a chromosomal segment

What are the consequences of chromosomal deletions?

• no copy of specified gene (imbalance of gene product)

• Pseudodominance

• Haploinsufficiency

Pseudodominance

expression of a normally recessive gene

Haploinsufficiency

when a single functional copy of the gene doesn’t produce enough gene product to bring about a wild-type condition

number of possible chromosome combinations in gametes equation

2ⁿ=

Chromosomal Inversion

a segment of a chromosome is reversed end-to-end through breakage and rearrangement

Loops (Chromosomal Inversion)

A loop is formed in the area where the chromosome has the inversion

Is recombination possible with chromosomal inversions

No

Chromosomal Translocations

• sections of chromosomes are moved to non-homologous chromosomes

  • or within the same chromosome (very rare)

What is the key to chromosomal translocation?

movement is not between homologous chromosomes, but anywhere else

Recombination

sections of chromosomes are moved to homologous chromosomes

What is required for genetic variation?

Mutations

What are the 2 major classes of mutations?

germ-line mutations and somatic mutations

Germ-line mutations

• DNA change in reproductive cells (sperm or egg) that gets passed from a parent to their child

• mutation is present in every cell of the offspring's body and can be inherited by future generations

• everyone has 70-100 germ-line mutations

Somatic mutations

mutations in all other cells

• everyone has millions to billions of somatic mutations

De-novo mutations

mutations that are not in your parents

Effects of Mutations

• may lead to downstream consequences on proteins

• may but not always lead to phenotypic change

What is the degeneracy of the genetic code?

There are 64 codons but only 24 amino acids

• changes to codons mean the same thing

Does the degeneracy of the genetic code bad?

It is a feature that saves you!

• allows many mutations that have no consequences

Synonymous mutation

when a base change results in the same amino acid product

Nonsynonymous mutation

when a base change leads to a different amino acid product

• leads to a phenotypic change

Somatic nonsynonymous mutation

cell could do its job wrong or still work properly

• cell can die or cancer starts

  • cancer is rampant somatic mutation

Somatic synonymous mutation

no effect

Germ-line synonymous mutation

no effect on offspring

Germ-line nonsynonymous mutation

mutant offspring

• different protein; phenotypic change

What are the three gene mutations in primary structure?

• base substitutions

• insertions and deletions (indels)

• expanding nucleotide repeats

Base Substitution (point mutation)

a nucleotide pair gets replaced with a different nucleotide pair

• A is substituted with a G

  • creates a G-T mismatch temporarily that gets fixed

Transition mutation

substitution of like base

• Pyrimidine switches with a pyrimidine

  • C switches with a T (vice versa)

Purine switches with a purine

• G switches with an A (vice versa)

4 options

Transversion mutation

a purine is switched with a pyrimidine (vice versa)

• A switches with C or T

• C switches with A or G

• T switches with A or G

• G switches with C or T

substitution of unlike base

What is the ratio of transversion to transition in humans?

1:2 Transversion to Transition

What is more likely to be synonymous, transitions or transversions and why?

Transitions because have no functional difference most of the time

• 3rd codon position codes for the same base most of the time (chemically redundant)

• pyrimidines (C and T) are more similar structurally

Insertions

mutation in which extra base pairs are inserted into a new place in the DNA

Deletions

mutations in which a section of DNA is lost, or deleted

Are insertions and deletions (indels) tolerable?

Yes for the most part

What occurs if the indel is a multiple of 3?

it adds/subtracts an amino acid

Frameshift mutation

caused by indels of a number of nucleotides in a DNA sequence that is not divisible by three

• alters the reading frame of all codons downstream of the indel

Expanding nucleotide repeats

mutation that leads to runaway repeats in one copy

• hairpin loops forms and causes part of the template strand to be replicated twice

  • increases the number of repeats

Fragile X

expanding repeat mutation that causes a fragile site at the ends of the X chromosome

Missense mutation

nonsynonymous mutation that converts an amino acid into a different amino acid

Nonsense mutation

nonsynonymous mutation where a sense codon turns into a stop codon

• translation stops prematurely

Silent mutation

a synonymous mutation where codon turns into a codon that produces the same amino acid

Why are most mutations recessive?

Most mutations are loss-of-function mutations where a gene product can’t do its job anymore

Loss-of-function mutation

gene product becomes partially or wholly inactivated

• deletion of all or part of a gene and a amino acid substitution that inactivates the protein

• allele has a complete loss of function

ex: lactose intolerance

not always bad

Gain-of-function mutation

• rare dominant mutation

• an altered gene product has a new function or pattern of gene expression

• usually caused by expression in a new tissue type or time of expression

• not always good

What is an example of a Gain-of-function mutation?

Ectopic expression in fruit flies (drosophila)

• expression of an eye on the elbow of the fly

• technically not good

Supressor mutation

a second mutation that reverts the phenotypic effects of an already existing mutation

• restores the phenotype seen prior to the original background mutation

Intragenic suppressor

• occurs in the same gene as the mutation

• often reverts amino acid or restores a frameshift

• ex: first a mutation of A and then a second mutation of A

Intergenic suppressor

mutation in a second gene separate from the gene of the original mutation

• changes how much mRNA is translated

ex: mutation in A and then a another mutation in B

Example of an intergenic suppressor

(a) The wild-type sequence produces a full-

length, functional protein.

(b) A base substitution at a site in the same

gene produces a premature stop codon,

resulting in a shortened, nonfunctional

protein.

(c) A base substitution at a site in another

gene, which in this case encodes tRNA,

alters the anticodon of tRNATyr; tRNATyr

can pair with the stop codon produced by

the original mutation, allowing tyrosine to

be incorporated into the protein and

translation to continue.

Mutation Rate

frequency with which a wild type allele at a locus turns into a mutant allele

Do all organisms have the same mutation rate?

No, different organisms have different mutation rates

• rates can vary with a species and within the genome

• even different parts of the body have different mutation rates

Are mutations intentional?

No, they are random and not for adaptive benefit

Spontaneous mutations

arise from a variety of sources

• errors in DNA replication

• spontaneous lesions

• transposable genetic elements

Induced mutations

caused by damage to DNA through exposure to ultraviolet/ionizing radiation or chemical mutagens

Mutagen

any agent that causes an increase in the rate of mutation above the spontaneous background

• UV (pyrimidine dimers)

• ionizing radiation

• chemical mutagens

• X-rays

Effects of radiation and mutagens

causes DNA damage that interferes with repair mechanisms

• increasing rates of mutation

True or False: Every individual of the same species would have chromosomes that appear similar in karyotype

True, generally have the same number, size, and shape of chromosomes, so their karyotypes appear similar.

Do additional copies of a gene cause cellular problems?

Sometimes

Are germ-line and somatic mutations both passed on to offspring?

No, only germ-line mutations (in eggs or sperm) can be inherited. Somatic mutations occur in body cells and are not passed on to offspring.

Somatic and germline mutations are classified based on

tissue type