Learn: Evanth 330 Exam 1

Tinberg's 4 Questions

How do we explain a trait, function, or disease?

- Proximate (How?) & slince-in-time: mechanism

- Proximate (How?) & historical sequence: development

- Ultimate (Why?) & slince-in-time: function

- Ultimate (Why?) & historical sequence: evolutionary history

Covalent bonds

When atoms share valence electrons; strongest type of chemical bond

Nonpolar molecules

Formed by covalent bonds when electrons are equally shared; water insoluble

Polar molecules

Formed by covalent bonds in which the electrons are unequally shared, have positive pole and negative pole; water soluble

pH scale

Neutral: pH = 7

Basic/Alkaline: pH > 7 (low H+)

Acidic: pH < 7 (high H+)

Ionic bonds

- Electrons transferred between a metal and non-metal

- Attraction between positively charged ions (cations) & negatively charged ions (anions)

- Weaker than covalent bonds

Hydrogen bonds

Weak bond formed between two polar molecules based on opposite charges attracting (no electron sharing); holds DNA together

Carbohydrates

Major source of energy in the body, includes sugars and starches

Monosaccharide

"Simple sugar", one carbon ring (e.g., glucose, fructose)

Disaccharide

2 monosacharides joined by covalent bond (e.g., sucrose, lactose)

Polysaccharide

Starches formed by the covalent binding of several monosacharides

Lipids

Mostly nonpolar organic molecules; insoluble in water

Triglycerides

3 fatty acid chains and glycerol; used for energy

Phospholipids

2 fatty acid chains and phosphate; "head" is polar (hydrophilic) and "tails" are non-polar, form double layer cell membrane

Steroids

Hormones; produced in gonads and adrenal glands from cholesterol

Saturated Fats

Solid at room temperature, no double carbon bond

Unsaturated Fat

Liquid at room temperature, has double carbon bond(s)

Proteins

- Chains of amino acids (20 different amino acids,

- Amino acids are charged so they attract each other to form kinks and folds in the protein

- Many functions: structure, enzymes, carriers, transporters, hormones, and neurotransmitters

Nucleic Acids

DNA or RNA made of a pentose sugar, phosphate group, nitrogenous base (purine or pyrimidine)

Nucleus

Holds DNA (chromosomes)

Plasma Membrane

Movement into and out of cells; involved with receptors and signaling

Smooth endoplasmic reticulum

Involved in lipid synthesis, some detoxifying abilities, and stores Ca2+ in striated muscle cells

Golgi complex

Processes proteins and lipids, makes vesicles, and prepares molecules to move out of cell

Mitochondrion

Release energy from food and transform into usable ATP

Lysosomes & Peroxisomes

Digest foreign molecules and worn and damaged organelles

Ribosomes

Synthesize proteins from mRNA

Rough endoplasmic reticulum

Involved in protein synthesis

How do molecules move into and out of cells?

- Phospholipids form a bilayer: polar heads face the inside or outside of the cell and nonpolar tails face toward center of membrane

- Proteins can go through membrane (integral) or be only on surface (peripheral)

Simple Diffusion

- Small, lipid-soluble (non-polar) molecules easily pass through membrane (O2 & CO2; steroid hormones)

- Water molecules are polar, but do not carry a charge & are small, so can pass through plasma membrane slowly (osmosis)

- Charged ions can pass through ion channels that cross the plasma membrane

Aquaporins

Integral channel proteins in membrane that allow water to diffuse through

Diffusion

Movement of solutes from high to low concentration

Facilitated Diffusion

Net diffusion from high to low concentration, no ATP used (no energy expended)

- Some molecules (glucose) can pass through specific carrier-mediated integral proteins ("lock and key" specificity)

- Transport proteins may always exist in the plasma membrane or be inserted when needed

Active Transport

Sometimes molecules must be moved from low to high concentration ("uphill"), requires energy from ATP

- Often called "pumps"

Bulk Transport

Endocytosis and exocytosis

Endocytosis

Vesicle forms and brings in materials (pathogens); portions of membrane removed

Exocytosis

Vesicle fuses and releases contents (digestive enzymes, hormones, neurotransmitters); portions of plasma membrane replaced

Gap Junctions

Allow adjacent cells to pass ions and regulatory molecules

Synaptic signaling

Nerves "innervate" organs, releasing neurotransmitters across a synapse to target cells

Paracrine signaling

Cells within an organ secrete hormones that diffuse to nearby target cells

Endocrine signaling

Glands secrete hormones into the bloodstream; only specific target cells can respond

Receptors

A target cell receives a signal because it has specific receptor proteins for that molecule on plasma membrane or inside cell

- Large, polar signal molecules (such as epinephrine, acetylcholine, insulin) bind to receptors on membrane

- Nonpolar signal molecules such as steroid hormones can penetrate plasma membrane and interact with receptors inside the cell

Leptin

A hormone produced by fat cells that reduces hunger; if no receptor -> no signal -> mouse becomes fat

Homeostasis Basics

Sensors in the body to detect change and send information to the integrating center, which assesses change around a set point and signals an effector, which makes adjustments to return to set-point

Negative Feedback Loops

Action of effectors reduces their production; they stop (or limit) themselves

Positive Feedback Loops

- Action of effectors amplifies the changes that originally stimulated the effectors

- Positive feedback could not work alone to maintain homeostasis, but it does contribute to many negative feedback loops

Homeostasis

Body responds to perturbations by defending a set-point, returning to "normal" range

Allostasis

Chronic perturbations push body to altered (and unhealthy) set-point

Testosterone Case Study

- Molecule type: lipid, non-polar

- How does it enter: passes through membrane, receptors in cytoplasm

- How is it regulated: H-P-G Axis, negative feedback loop

Acetylation

The opening up and exposing of DNA for transcription

- DNA in most of the chromosome is tightly wound around histones and not available for transcription of proteins

Alternative Splicing

Splicing at different points creates different sequences & proteins; introns are spliced out and exons remain

Nucleotide bases

DNA: Adenine, cytosine, guanine, thymine

RNA: uracil instead of thymine

Regulatory Genes

Transcription factors, enhancers

- Determine the activity of protein coding genes; big effects on phenotype

Meiosis

Producing gametes: sperm and eggs

- Recombination: maternal and paternal chromosomes mixed

Reproduction

Passing DNA from parent to offspring

- Sperm: 23 chromosomes, mtDNA in tail

- Egg: 23 chromosomes, mtDNA inside

- Embryo: 46 chromosomes, 2 sets of 23 and mtDNA from mother

Mendel's Rules of Inheritance

Works for a small number of simple traits

- You have 2 copies of each gene, one inherited from the biological mother and one from the biological father

- These may be the same alleles (versions of the gene) or they may be different

- Together these alleles determine the phenotype

independent assortment: genes for different traits inherited independently

Pleiotropy

One gene has many effects

Complex traits

Genotype x Environment = Phenotype

How we assess the relative influence of Genes and Environment?

Concordance: % Similarity between pairs

= similar pairs (both have traits)/ total pairs

Heritability

Proportion of the variance in a trait that can be explained by genetics within a given sample at the time of study

- h2 = 0.0 environment explains all variation in the trait in this particular sample

- h2 = 1.0 genetics explains all variation in the trait in this particular sample

Is specific to the population and time it was measured, can change over time; does not tell us about between-group differences

Genome Wide Association Studies (GWAS)

- Start by measuring 100,000 - 1,000,000 SNP's

- Test which SNP's correlate with a certain Phenotype

- Develop a "Polygenic Risk Score" (and validate it in a different dataset)

Single Nucleotide Polymorphism: a common variant (substitution or deletion) of a single base in the genome

GWAS Strengths

- Examines whole genome

- Uncovers tiny contributions

- Point to critical physiology

GWAS Weaknesses

- Only useful for population in study (most studies: only European)

- Can miss effects of very rare alleles

- Can't fully control for environment

- Can be misused for racist or eugenic purposes

- Low predictive power for most individuals

Evolution

Change in frequency of alleles over time

Four Forces of Evolution

Mutation, drift, flow, and natural selection

Necessary conditions for natural selection

1. There must be variation in the trait

2. The trait must be heritable (shaped by genes)

3. Variation in the trait must affect fitness

Fitness

Probability of producing surviving offspring

- Usually measured as the Number of Surviving Offspring Produced

- Fitness is measured relative to others in the population

Naturalistic Fallacy

Natural doesn't always mean "good"; biology tells us how things work, not how they ought to work

Homology

Similarity due to common ancestor

Spandrels

Neutral traits that are by-products of selection for something else

Vestigial Traits

Neutral, left-over traits that were adaptive in ancestral species

Embryology: General Framework

Stage 1. Fertilization to Implantation

Stage 2. Gastrulation and Neurulation

Stage 3. Organogenesis and Limb Development

Fertilization

Coming together of egg and sperm (female: larger gamete, male: smaller gamete)

- Implantation occurs outside ovary in distal fallopian tube

- Male and female pronucleus eventually fuse

- At 6 days, implantation by trophoblast cells in uterine wall

Blastocyst

Ball of cells (5-6 days post-fertilization) that forms in early embryonic development

- Consists inner cell mass (embryoblast that becomes embryo) and an outer layer (trophoblast that becomes placenta)

Compaction and formation of the blastocyst when morula ~60 cells, divides via mitosis

Monozygotic Twins

Form when the early embryo divides (cleavage); timing of cleavage affects embryo & placenta development

Dizygotic Twins

Form when two eggs are fertilized; the develop separately

Heteropaternal superfecundation

Fertilization by sperm from two males (results in 2 embryos); exceedingly rare (but documented) in humans

Bilaminar germ disc

Amniote embryo prior to gastrulation; consists of epiblast and hypoblast layers

Gastrulation

Formation of the 3-layer embryo

- Epiblast cells migrate to groove called primitive streak (focalized at primitive node) and dive into to form mesoderm and endoderm

- Epiblast becomes ectoderm

Layers (top to bottom): ectoderm, mesoderm, and endoderm

Neurulation

Formation of the neural tube (for brain & spinal cord)

Gut tube formation

Folding of the embryo: incorporation of the yolk sac endoderm, surrounded by mesoderm and further lined by ectoderm

Gastrulation and Neurulation

- Disc folds to form two tubes: one for guts, other for brain and spinal cord

- As neural tube "zips", location of vertebrae can be seen

HOX genes

Series of genes that determine the basic body plan; 500 million years old and conversed across all animals

Cervical vertebrae

All mammals have 7 cervical vertebrae (except manatees and sloths), strong stabilizing selection

Lumbar vertebrae

- Increased lumbar number (directional selection) in humans

- Strong stabilizing selection favoring 5

Getting a Head

Heads of all vertebrates built from the same parts

- 3 bulges called pharyngeal arches (aka gill arches, early precursor for gills in fish) -> become structures around head and neck

Face development

~8 weeks, gill arches meet in middle, fusion of left and right sides visible in philtrum

- If fusion does not occur: cleft palate

- ~240 genes associated with face shape, most are neutral (some evidence for selection in nose shape)

Fate of ectoderm

Epidermis (skin), brain & spinal cord, nerves, hair, and skull

Fate of mesoderm

Muscles, vertebral column, limbs, heart and vessels, kidneys, and genitals

Fate of endoderm

Gastro-intestinal tract, liver, lungs, and bladder

Lung Evolution

Human lungs develop from guts (develop from endoderm) because they are an evolved fish air bladder

Fetal circulation

Membrane between mother and babies allows baby's blood to be oxygenated, bypasses allow baby's blood to bypass lung, which do not work until birth

Limb development

Limb buds visible by 4th week, location determine by HOX genes expression (diffusion gradients allow identification and segmentation of body plan)

Ossification

Process of bone formation

Membranous bone

Cells ossify: skull and clavicle

Endochondral bone

Bone that begins as cartilage that is subsequently replaced by bone tissue

Osteoclasts

Cells that break down bone

Osteoblasts

Bone forming cells

Bone growth

- Occurs at the boundary between the diaphysis and epiphysis (growth plate)

- Cells are pushed into growth plate, and then cells are pushed into both directions away from growth plate

- Ossify from bottom up or top down

- When waves of ossification meet in middle and fuse together, growing stops

Saltatory growth

"Jumps" with periods of stasis

Epiphyseal Fusion

The process of ossification where the shaft and ends of a long bone fuse together, the extent of which can be used to age a juvenile skeleton joints