Genetics Exam 1

Hippocratic school of medicine

“Humors” derived from different parts of male body serve as bearers of hereditary traits. Can either be healthy or diseased and change throughout life.

Aristotle

Semen contains a vital heat that cooks and shapes menstrual blood into an embyro. (Hints at epigenesis)

Epigenesis

Cells start out undifferentiated

Homunculus Theory

Sperm contains a perfectly formed mini human

Ovist Theory

Egg cell contains a perfectly formed mini human

William Harvey

First modern explanation of epigenesis

August Weissman / Germ plasm theory

Proposed that ovaries and testes each contain full sets of genetic info and that sperm and egg cells carry info brough together in fertilization.

Edmund Beecher Wilson

Proposed nuclein is the hereditary material, inheritance may be affected by transmission of a chemical compound to offspring

Archibald Garrod

First to characterize a genetic disorder

Alkaptonuria = “Black Urine Disease”

Defect in HGA breakdown

Cell Theory

All life is made of cells

All cells come from other cells

Spontaneous generation / Pasteur

Life will arise de novo from non-living substances

Fixity of Species

Idea that all species have not changed since their inception

Schleiden and Schwann

All life is made of cells

Rudolph Virchow

All cells come from other cells

Premises for natural selection (Darwin + Wallace)

Species are variable and some of this variation is heritable.

Some of this heritable information is meaningful in terms of survival and reproduction.

Species tend to “over-reproduce”.

Conclusions for natural selection argument

There will be a struggle for existence among offspring

Individuals with better suited traits will enjoy higher reproductive success

Population will change through time as adaptive traits accumulate

Blending Inheritance (Darwin)

Offspring will tend to have trait values near the average of the parents

Fleeming Jenkin

Stated that adaptive evolution is not compatible with blending inheritance because it does not matter how advantageous a new variant is, it will tend to be diluted out each generation.

Gregor Mendel

Inheritance was particulate not blending.

Beginning of modern genetics

Chromosomes

Carries genetic information in form of genes

Homologous pairs

Maternal and paternal copies of a chromosome.

Human diploid = 46, contains 23 homologous pairs

Contain same genes although alleles will differ

Genes

Functional unit of heredity

Alleles

Alternative forms of the same gene

Mitosis

Replication and equal division of chromosomes into two daughter cells. (2N)

Meiosis

Two rounds of division yielding 4 haploid gametes. (1N)

Gametes

Reproductive cells

Sutton and Boveri

Found behavior of chromosomes to be analogous to how mendel described behavior of genes during gamete formation.

Hypothesized genetic info is encoded on chromosomes.

Chromosomal Theory of Inheritance

Genetic information is encoded on chromosomes, Sutton and Boveri

Willam Bateson

Supporter of the universality of mendelian inheritance.

Convinced by a paper he read in 1901 describing a genetic disease. (Garrod)

Universality of Mendelian Inheritance

All traits are fundamentally inherited according to the rules of mendelian inheritance.

Debate on Inheritance

Biometricians believed that continuous characteristics, like height or weight, could not be explained by this theory.

Herman Nilsson-Ehle and Edward East

Work showed that Mendelian inheritance could actually explain inheritance of continuous characters if traits are governed by multiple mendelian factors.

Mutation

Any heritable change, source of ALL genetic variation.

White Eye Mutation

Mutation of the eyes in dropsophila.

First mutation that was truly studied, confirmed chromosomal theory of inheritance.

Gene for eye color was mapped to X chromosome and there are 2 alleles, one red and one white.

Genotype

Genetic makeup of an organism

Refers to alleles that are present for one particular gene

Phenotype

The physical expression of a genotype

Chromosome Makeup

50% DNA and 50% Proteins

ATGC, monomers in DNA

20 monomers in proteins (AAs)

Experiments by Avery, McCarty, and MaCleod

Demonstrated that DNA was hereditary material rather than the more complex proteins.

Nucleotide

Basic unit of DNA and RNA

Three Components

Jointed into polymers via covalent phosphodiester bond

Components of a nucleotide

Phosphate

Ribose/Deoxyribose Sugar

Nitrogenous base

Phosphodiester Bonds

3’ Carbon - P - 5’ Carbon of another nucleotide

DNA Structure

Exists as a complementary(A-T, G-C), antiparallel, duplex held together by hydrogen bonds.

RNA Structure

Ribose

Uracil instead of Thymine

Single Stranded

Can form complementary structures with DNA

DNA + RNA

DNA contains hereditary information while RNA brings this information to the ribosomes.

DNA is transcribed into RNA, RNA is translated into proteins.

tRNA

Translates the language of DNA/RNA into the language of a protein

Central dogma of biology

DNA → Transcription → RNA → Translation → Protein

Proteins

Perform cellular functions that are coded for by DNA

Sickle Cell Disease

Mutation within Hemoglobin

A single nucleotide change alters the amino acid sequence

Causes hemoglobin to polymerize which results in fragile sickle shaped red blood cells

CHANGES IN DNA WILL MANIFEST WITHIN THE RNA WHICH WILL THEN ALTER THE PROTEIN, ALTERING THE PHENOTYPE

Gel Electrophoresis

DNA fragments of different sizes can be differentiated based on their migration pattern through the gel.

LUCA

Last universal common ancestor

All life shares a common ancestor, thus learning about a gene in one organism is usually transferable to humans

Genetic Model Organisms

Bacteria, yeasts, fruit flies, mice, nematodes

Fast generation times and easy to genetically manipulate

Sequenced alongside human genome during Human Genome Project

Evidence for LUCA

Composed of a common set of chemical parts and structures

Contain genetic information that uses nearly universal code

Extract energy from environment

Replicate genetic matter similarly

Share structural similarities

Evolve through gradual genetic changes

Carl Woese

Examined rDNA genes, common to all forms of life, and based on similarity devised the three domain model of life on earth

Three domain model

Bacteria, Archaea, Eukarya (mitochondria and chloroplasts).

Plasma Membrane

Delimits the cell from its external environment

Cell Wall

Found in plants, made of cellulose

Glycocalyx

Common in Animal cells

Outer layer made of glycoproteins and polysaccharides

Provides biochemical identity to cells and the components that give this identity are genetically controlled.

Receptor Protein

Found on surface of cell membrane

Transfer chemical signals across the membrane

Cytoplasm

Everything outside of nucleus

Contains organelles and cytosol

Cytosol

Contains many tubules and filaments that give the cell its shape. (Cytoskelton)

Microtubules

Made of the protein tubulin

Microfilaments

Made of the protein actin

Rough ER

Ribosomes present

Site of synthesis(translation) of membrane proteins and proteins destined for exportation.

Smooth ER

No Ribosomes

Site of fatty acid and phospholipid synthesis

Free ribosomes

Unbound ribosomes within the cytoplasm

Mitochondria

Site of oxidative phosphorylation

Where most ATP is produced in eukaryotes

Encodes own set of genes (mtDNA), transcribes and translates own proteins

Chloroplasts

Structure associated with photosynthesis

Encodes own set of genes (cpDNA), transcribes and translates own proteins

Endosymbiosis

Mitochondria and Chloroplasts are examples of this within bacteria.

Eukaryotes

Nucleus + Membrane bound organelles

Prokaryotes

No nucleus + membrane bound organelles

No mitochondria or chloroplasts

Singular circular chromosome, contains rRNA genes.

Nucleus

Membrane bound structure that houses genetic material

Nuclear envelope

Membrane around nucleus

Two lipid bilayers

Nucleolus

Where ribosomal RNA (rRNA) is made and first steps of ribosome assembly occur.

Nucleolar organizer region

Region of DNA where rRNA is encoded

Nuclear Pore

Where molecules enter/exit the nucleus

Chromatin

How DNA is loosely packaged in the nucleus outside of mitosis and meiosis

Diffuse network of DNA and associated proteins within the nucleus in a non-condensed form

Centromere

Constricted region of a chromosome (where the two chromatids cross)

Specialized DNA sequence that serves as site of a protein complex called kinetochore, site of spindle attatchment.

P + Q arm

Caused by centromere division of chromosome

p-arm is short, q-arm is longer

Qualitative classification of Chromosomes

Based on location of centromere

Metacentric = Middle

Submetacentric = Between middle and end

Acrocentric = Close to end

Telocentric = At end

Diploid

Each cell contains two complete sets of genes, and thus one of each chromosome.

Humans: 46 chromosomes = 23 homologous pairs

Biparental Inheritance

For each pair of chromosomes, one is derived paternally and the other maternally.

Sister chromatids

Products of a chromosome that has replicated

Identical sequences

Homologous chromosomes

Contain same genes but are derived from different parents.

Chromosome number

Differs between species

Does not correlate well with genome size or complexity

Mitosis

One cell replicates into two genetically identical daughter cells.

Basis for asexual reproduction

Karyokinesis

Separating the replicated genetic material evenly.

Interphase

Portion of cell cycle that does not include mitosis

G1, S, G2

G1, G2

Phases of interphase where the cells grow with high levels of metabolic activity

G2 brings prep for mitosis

S Phase

Replication of DNA occurs

Prophase

Centrioles move to opposite ends of cell to an area called the centrosome

Nuclear envelope begins to break down

Chromosomes condense

Sister chromatids are formed

Centrioles

Organelles made mostly of tubulin that organize the microtubules into spindle fibers for mitosis.

Prometaphase

Centrioles reach opposite poles

Spindle fibers form, dispersing from centromere (some are used for chromosome movement others stabilize cell)

Kinetochore binds centromere

Cohesin is degraded by separase

Occurs everywhere except centromere (protected by shugoshin)

Sister chromatids reach metaphase plate (center of cell)

Cohesin

Holds chromosomes together along their length in prophase

Separase

Degrades cohesin in prometaphase everywhere except centromere.

Metaphase

Moment when all chromosomes are aligned on metaphase plate

Centromeres are aligned

Anaphase

Sister chromatids are disjoined

Shugoshin unbinds the centromer, allowing breakdown of cohesin by separase

Separated chromosomes are called daughter chromosomes

Chromosome separation accomplished by molecular motors that shorten spindle fibers

Telophase

Complete sets of chromosomes on both ends of cell

Cytokinesis separates cell into two, constriction of cell membrane along metaphase plate forming a cell furrow.

Nuclear envelope reforms, chromosomes decondense, Nucleolus becomes more visible.

Cyclins

Main proteins in cell cycle

Bind to CDKs activating them and allowing them to phosphorylate their targets, continuing the cell cycle

G1/S Checkpoint

Cell size must be sufficiently large

DNA must not be damaged

G2/M Checkpoint

DNA replication must be complete

Detected DNA damage must be repaired