Biology: Mitosis, Meiosis, Non-Mendelian Genetics, Evolution of Y

Homologous Chromosomes

A matched pair of separate chromosomes

Sister Chromatid

Identical copies of a single chromosome

Chromosome

A thread-like structure made of DNA and proteins that carries an organisms genetic information.

Autosomal Chromosome

• Control the traits found in somatic cells

• 22 pairs in humans

• Always homologous

• Do not determine the biological sex of an individual

Sex Chromosome

• Determine biological gender and carry sex-linked traits

• 1 pair in humans

• Homologous in females, non-homologous in males

• Chromosomes that do determine the biological sex of an organism

Monad Chromosome

• Consists of one single unreplicated sister chromatid.

Dyad Chromosome

• A duplicated chromosome made of two identical sister chromatids attached by a centromere.

Tetrad (bivalent)

A group of four sister chromatids that are formed by paired homologous chromosomes.

Diploid

Two complete sets of chromosomes (2n) | Human = 46, Fruit Fly = 8

Haploid

One complete set of chromosomes (n) | Human = 23, Fruit Fly = 4

Kinetochore

The central attachment point for the spindle fibers.

Chiasmata

The X-shaped site where homologous chromosomes are physically connected to during meiosis.

Metacentric Chromsome

Centromere is in the exact middle of the chromosome.

Submetacentric Chromosome

Centromere is slightly off center in the chromosome.

Acrocentric Chromosome

Centromere is near one end of the chromosome.

Telocentric Chromosome

Centromere is at one end of the chromosome.

Centromere

The region of a chromosome that links a pair of sister chromatids together.

Karyotype

A karyotype is an individual’s complete set of chromosomes. There are 23 chromosome pairs and 46 chromosomes in the typical human karyotype.

Cell Cycle: Interphase Stages

• G₀ Phase

• G₁ Phase

• S Phase

• G₂ Phase

Cell Cycle: G₀ Phase

• No division occurs

• Pauses cell cycle

• Cell functions normally

Cell Cycle: G₁ Phase

• Cell grows larger in size

• Makes copies of their organelles

Cell Cycle: S Phase

• Cell Duplicates its DNA

Cell Cycle: G₂ Phase

• Cell grows even larger

• Reorganizes to prepare for mitosis

Cell Cycle: Mitosis (Mitotic Phase)

• Nuclear separation

• Results in identical daughter cells

• Same exact ploidy

• Equational division

Cell Cycle: Prophase

• DNA condenses into chromosomes

• Spindle fibers start to form

Cell Cycle: Metaphase

• Chromosomes line up at the cell’s equator

• Spindle fibers attach to chromosomes

Cell Cycle: Anaphase

• Spindle fibers retract

• Sister chromatids are pulled apart towards opposite ends of the cell

Cell Cycle: Telophase

• Two new nuclear membranes form around the separated DNA

Cell Cycle: Cytokinesis

• Cytoplasm splits in half

• Creates two new independent and identical daughter cells

Cell Cycle: Meiosis I

• Homologous chromosomes separate

• Reductional Division

• Results in two haploid (1n) daughter cells

• Daughter cells have 23 chromosomes, 0 homologous pairs, 23 centromeres, 46 chromatids

• The chromosomes of the daughter cells still have two chromatids per chromosome

Cell Cycle: Prophase I

• Chromosomes condense and pair, crossing over occurs, spindle fibers form.

• Leptotene Stage

• Zygotene Stage

• Pachytene Stage

• Diplotene Stage

• Diakinesis Stage

Prophase I: Leptotene

• Chromosomes condense

• Telomeres attach to the inner nuclear membrane

Prophase I: Zygotene

• Matching maternal and paternal chromosomes find each other and pair up side by side.

• Proteins hold the chromosomes together in a tetrad.

Prophase I: Pachytene

• Crossing over occurs

• Non-sister chromatids exchange pieces of DNA

Prophase I: Diplotene

• Separation begins, homologous chromosomes start to pull away.

• Homologous chromosomes are locked (arrested) at the X-shaped sites where crossing over occurs (the chiasmata).

Prophase I: Diakinesis

• Chromosomes reach their most condensed state

• Nucleolus fades

• Nuclear envelope breaks down so that spindle fibers can attach.

Cell Cycle: Metaphase I

• Pairs of homologous chromosomes line up along the middle of the cell

• Spindle fibers attach to the chromosomes

Cell Cycle: Anaphase I

• Spindle fibers retract

• Homologous chromosome pairs segregate towards opposite ends of the cell

Cell Cycle: Telophase I & Cytokinesis

• Chromosomes gather at opposite poles

• Cell divides into 1n daughter cells with 23 paired-chromatid chromosomes

Cell Cycle: Meiosis II

• Sister chromatids separate

• Equational division

• Results in four haploid (1n) daughter cells

• Daughter cells have 23 chromosomes, 0 homologous pairs, 23 centromeres, 23 chromatids

• The chromosomes of the daughter cells have only one chromatid per chromosome

Cell Cycle: Prophase II

• Chromosomes condense

• Nuclear envelope breaks down, nucleoli disappear

• Chromosomes duplicate and move towards opposite poles of the cell, forming new spindle fibers

Cell Cycle: Metaphase II

• Chromosomes line up individually along the equator

• Spindle fibers attach to the chromosomes

Cell Cycle: Anaphase II

• Centromeres split, sister chromatids segregate.

• Spindle fibers retract, bringing the sister chromatids towards opposite sides of the cell.

Cell Cycle: Telophase II & Cytokinesis

• Chromosomes gather at opposite poles

• Cell divides into 1n daughter cells with 23 single-chromatid chromosomes

• Nuclear envelope reforms, chromosomes decondense

• Cytokinesis splits the cytoplasm

Synapsis

Synapsis is the pairing/alignment of two homologous chromosomes.

Non-Disjunction

When chromosomes fail to separate equally during anaphase.

Trisomy

When a gamete contains an extra chromosome as a result of non-disjunction.

Chromosome Theory of Inheritance

Genes are located on chromosomes and the behavior of those chromosomes during meiosis explains the inheritance of the traits within such chromosomes.

Euchromatin vs Heterochromatin

• Euchromatin: loosely packed, more accessible, more active, higher expression.

• Heterochromatin: tightly packed, less accessible, more inactive, lower expression

Sex-Linked Gene

Genes located exclusively on the X and Y chromosomes.

Hemizygous

Having one copy of a gene rather than two (males with the X chromosome)

Dosage Compensation

• A process that equalizes the expression of genes on sex chromosomes between individuals with different numbers of X chromosomes.

• In females the second X chromosome is largely inactivated, helping prevent the double expression of X-linked genes.

Y-Chromosome: Start of Divergence

• The X and Y chromosomes began diverging ~300mya

• The Y chromosome started as an autosomal chromosome which was almost identical to the X chromosome

• Started when the SOX3 gene mutated into the SRY gene.

Y-Chromosome: Three Main Gene Classes

• SRY Gene: testis development

• RPS4Y Gene: cell housekeeping

• DAZ Gene: sperm production

Y-Chromosome: Inversion Event

• The early Y-chromosome inverted itself

• Recombination was practically impossible

• Solved by pseudoautosomal regions at the ends of the X and Y chromosomes

Y-Chromosome: Gene Duplication

• Y-chromosome creates additional copies of genes

• Provide more functional support for male-specific functions

• Evolve new functions

• Produce multiple copies of genes important for sperm production

Pseudoautosomal Region

• Regions at the ends of the X and Y chromosomes

• Homologous; can stil undergo recombination during meiosis

Map Unit (m.u.) / Centimorgan (cM)

• A unit of measurement in gene linkage used to measure the relative distance between genes and markers on a chromosome

• One map unit between two genes is equal to one percent recombination

• 1 m.u. between two genes means that there is a one percent chance that a crossover event will happen between the two during meiosis.

χ² (chi-squared)

• Σ[(observed - expected)² / expected]

• If χ² is less than c.v., fail to reject H₀

• If χ² is greater than c.v. reject H₀

Gene Linkage: Recombination Frequency

• Determine parental genotypes, for any given gene pair (a-b, b-c, etc) determine the number of recombinants

• To determine the number of recombinants, find all progeny where the given gene pair occurs on separate sides of the chromosome relative to the parental genotype.

• Example: parentals are a b⁺ c⁺ / a⁺ b c | for a to b, find all progeny that are ab or a⁺b⁺ | for b to c, find all progeny that are b⁺c or bc⁺.

Gene Linkage: Linkage Map

A method used to visualize and organize the relative distances (recombination frequencies) between three or more genes.

Gene Linkage: Interference

• Interference is where the recombination (crossover event) of one gene influences the probability of recombination (crossover event) in another gene.

• Interference = 1 - Coefficient of Confidence

• Coefficient of Confidence = (# of observed double crossover events) / (# expected double crossover events)

• # Expected DCO = (recombination frequency of gene a)(recombination frequency of gene b)(recombination frequency of gene n)(total number of progeny

Gene Linkage: Gene Order

• Determine the parental gene types

• Determine the double crossover types

• Pair the ones that match two of the genes

• Whichever gene is flipped in both is in the middle

Gene Linkage: Coupling

A gene arrangement where dominant (wild-type) alleles and recessive (mutant) alleles sit with their matching inheritance type allele on opposite sides of the chromosome (AB/ab).

Gene Linkage: Repulsion

A gene arrangement where dominant (wild-type) alleles and recessive (mutant) alleles sit with their non-matching inheritance type allele on opposite sides of the chromosome (Ab/aB).

Codominance

• Two different alleles are both expressed in a distinct manner

• Homozygous BB: Black Color

• Heterozygous Bb: Peppered Black and White Color

• Homozygous bb: White Color

Incomplete (Partial) Dominance

• Two different alleles result in a mixed/blended phenotype of both genes.

• Homozygous RR = Red Color

• Heterozygous Rr = Pink Color

• Homozygous rr = White Color

Loss of Function Mutation

• Recessive mutations, no functional protein to affect phenotype

• Null or amorphic allele results in a total loss

• Hypomorphic allele only results in a partial loss

Gain of Function Mutation

• Dominant mutations, new protein is made that affects phenotype

• Takes effect regardless of wild-type allele

Mutant Allele

Anytime when existing allele is changed to new genetic state, a change in the DNA sequence.

Gene Action

Interaction between genes and the expression of phenotype from genotype.

Penetrance

The proportion of a population carrying a specific gene variant that actually exhibit the associated phenotype.

Incomplete Penetrance

Incomplete Penetrance means that less than 100% of carriers actually show the trait.

Complete Penetrance

Complete Penetrance means that all individuals with the genotype show the trait.

Expressivity

The degree of expression of a penetrant phenotype

Variable Expressivity

Individuals of the same exact genotype can experience different degrees of expression for the associated phenotype.

Uniform Expressivity

All individuals of the same genotype express the associated phenotype to the same exact degree.

Genomic Imprinting

For a given gene, the manifestation of the associated phenotype depends on which parent the gene was inherited from

Epigenetics

The study of how environmental and behavioral factors can cause changes that affect how genes are expressed without altering the underlying DNA sequence.

Pleiotropy

• Many symptoms or effects of a single gene mutation

• A single gene affects the expression of more than one phenotype

Epistasis

A collection of inheritance patterns wherein the expression of one gene is masked, inhibited, or modified by the expression of one or more other genes.

Epistasis: Epistatic Gene

The gene that does the masking or modifying of the hypostatic gene.

Epistasis: Hypostatic Gene

The gene whose phenotype is altered or hidden.

Epistasis: Dominant Gene Action

• 12:3:1

• One dominant allele eliminates two alternative alleles on a separate loci

Epistasis: Recessive Gene Action

• 9:3:4

• The allele causing epistasis is recessive, can occur at one or more points along the pathway

Epistasis: Duplicate Recessive (Complementary) Gene Action

• 9:7

• Presence of two genes are required to produce the end product

Epistasis: Duplicate Dominant (Redundant Gene Action)

• 15:1

• Dominant alleles at separate loci both produce the same phenotype

Epistasis: Dominant and Recessive (Inhibitory) Gene Action

• 13:3

• Dominant allele at one state and homozygous recessive alleles at another can both mask the expression of other genes

Epistasis: Additive Gene Action

• 9:6:1

• Genes on separate loci mix to form intermediate phenotypes

Molecular Markers: Polymorphism

The presence of two or more variant forms of a DNA sequence at a specific locus in a population.

Molecular Markers: Single-Nucleotide Polymorphism (SNP)

A difference of one nucleotide in a DNA sequence.

Molecular Markers: Variable Number Tandem Repeat (VNTR)

A location in the genome where a short nucleotide sequence is repeated back-to-back

Molecular Markers: Minisatellite Marker

• A type of VNTR

• 15 to 100 base pairs long

• 1 per 100,000 base pairs, or about 30,000 in the whole genome

• Same repeated sequence with approximately 5 to 50+ repeats

Molecular Markers: Microsatellite Marker

• A type of VNTR

• 2 to 5 base pairs long

• 1 every 30,000 base pairs

• Same repeated sequence with approximately 5 to 50+ repeats

• Useful as highly polymorphic DNA markers

• Mutate by replication error

Molecular Markers: Quantitative Trait Locus (QTL)

A statistical method that links two types of information—phenotypic data (trait measurements) and genotypic data (usually molecular markers)—in an attempt to explain the genetic basis of variation in complex traits.

Molecular Markers: Genome-Wide Association Study (GWAS)

• An approach used in genetics research to associate specific genetic variations with particular diseases.

• Involves scanning the genomes from many different people and looking for genetic markers that can be used to predict the presence of a disease.

• Helps with disease research and treatment strategies.

Slipped Strand Mispairing

A mutation process during DNA replication or repair where DNA strands misalign at short repetitive sequences, leading to insertions or deletions.

Sex-Linked Pedigree: Y-Linked

• Father passes the trait to all sons

• Hemizygous inheritance

• Only shows up in males

Sex-Linked Pedigree: X-Linked Dominant

• Mothers pass their X to both sons and daughters

• Fathers pass their x to only daughters

• Affected male outsiders are hemizygous

• Affected female outsiders are heterozygous unless proven otherwise

• Unaffected female outsiders are homozygous normal

• X^D = dominant mutant allele | X^d = recessive mutant allele

Sex-Linked Pedigree: X-Linked Recessive

• Mothers pass their X to both sons and daughters

• Fathers pass their X to only daughters

• Females express it only if they receive copies from both parents

• Males express it with only one copy

• Recessive in females

• Affected male outsiders are hemizygous

• Affected female outsiders are homozygous recessive

• Unaffected female outsiders are homozygous normal unless there is evidence that suggests otherwise.