Biology Chapter: Cell Division and Genetics

Selective Breeding

• Humans have been aware of genetics via selective breeding for over 10,000 years
• Examples include changing corn from small to large ears, and the evolution of dogs from wolves
• Selective breeding can have unintended negative consequences, such as physical issues in small toy dog breeds (Chiari Malformation)

Experiments and Main Outcomes

• Gregor Mendel, an amateur botanist, published and explained hereditary transmission in plants in 1866
• His work was rediscovered by three botanists in 1900 (Correns, De Vries, and Von Tschermak)
• Garrod described the inheritance of a human disorder, alkaptonuria
• Sutton and Boveri independently observed chromosome movement during cell division
• Griffith's experiment (1930s) demonstrated that one bacterium can take up genetic material from another and change its properties
• Avery, McLeod, and McCarty performed an experiment showing that DNA is the "transforming factor"
• Hershey-Chase experiment demonstrated that DNA is the genetic material
• 1960s: mechanisms of transcription and translation were defined, and the genetic code was deciphered
• 1970s: cloning and recombinant DNA technology advanced rapidly
• 1980s: genome study and comparison began
• 2001: the first published draft of the human genome became available

DNA Structure

• DNA is the genetic material
• It has a double-stranded structure (double helix)
• Complementary base pairing: A with T (2 hydrogen bonds), C with G (3 hydrogen bonds)
• DNA replication duplicates DNA prior to cell division
• Transcription uses one DNA strand to direct RNA synthesis

DNA Replication

• Semi-conservative method is the correct method of DNA replication
• DNA replication happens in synthesis phase (S phase) of cell cycle.
• Each strand of DNA serves as template for the new strand.

RNA

• RNA is a genetic material in some viruses
• Messenger RNA (mRNA) is responsible for translation into proteins at nucleoprotein structures called ribosomes
• RNA is single-stranded
• RNA's nitrogenous bases are Guanine, Adenine, Cytosine, and Uracil
• A pairs with U, and G pairs with C

Genes and Chromosomes

• Genes are physical units of heredity represented by DNA sequences
• Chromosomes are long DNA molecules and proteins containing genes.
• DNA is wrapped around histones, creating nucleosomes, which are found inside chromosomes.

Early Genetic Concepts

• Phenotype: observable traits of an organism
• Genotype: the genetic constitution of an organism
• Alleles: variant forms of genes

The Central Dogma

• DNA is replicated, transcribed into RNA, and translated into protein.
• DNA replication occurs in the nucleus.
• DNA-to-RNA (transcription) happens in the nucleus.
• In prokaryotes, translation happens in the cytoplasm.
• RNA-to-Protein (translation) happens in the cytoplasm
• RNA molecules can leave the nucleus through nuclear pores

DNA Translation, initiation, elongation, and termination

• Initiation—RNA polymerase starts, transcription bubble.
• Elongation—RNA polymerase moves along template strand and unwinds DNA; creates mRNA
• Termination—RNA polymerase recognizes the termination sequence and stops

RNA Translation

• In prokaryotes, ribosomes in the cytoplasm translate mRNA into protein
• In eukaryotes, ribosomes in the cytoplasm and endoplasmic reticulum translate mRNA into protein

The Genetic Code

• The genetic code—the relationship between codons and corresponding amino acids.
• There are 20 amino acids and 64 possible combinations of codons.
• AUG serves as a start codon

Darwin's Theory of Evolution

• Evolution theory that all organisms are related through common ancestry over time.
• Natural selection—a process where variations lead to differences in reproductive success.
• Variations are passed from one generation to another. 3 Main Principles:
• Variation of traits among members of a population.
• Variation of traits passed from one generation to the next.
• Certain traits provide a higher rate of survival and reproduction and are passed to the next generation.

Five Fundamental Forces of Evolution

• Mutation: source of genetic variation (new alleles)
• Selection: Differential reproductive success.
• Genetic Drift: Random allele frequency change, stronger in small populations.
• Migration (Gene Flow): Movement of alleles between populations.
• Nonrandom Mating: Probability of mating between two individuals in a population.

Genetic Variance

• Heritability: the fraction of variation due to genetics in a population. Measures how traits change over generations due to genetics.
• Inbreeding: increases the chances of deleterious recessive mutations combining in offspring.

Tracing Evolutionary Relationships

• Cladistic Approach: groups organisms into clades based on shared characteristics.
• Rooted Tree: reflects the most basal ancestor.
• Terminal nodes: organisms with data.
• Internal Nodes: points in evolution where organisms diverged.
• Ancestral Characters: inherited attributes like ancestors
• Derived Characters: features different from ancestors

Concepts of Monophyly, Polyphyly, and Paraphyly

• Monophyly: group of organisms descended from a single ancestor.
• Polyphyly: unrelated organisms from different ancestors.
• Paraphyly: includes a common ancestor but not all descendants.

Constructing Phylogenetic Trees using Molecules

• Phylogenetic trees are constructed based on shared DNA or protein sequences.
• Maximum parsimony: simplest scientific explanation used to infer trees.
• Sequence differences between organisms to determine relatedness, with the closest at the top.

DNA Replication: History, structure

• Photo 51: famous image of DNA double helix
• Watson and Crick: discovered the DNA double helix structure
• Bases along one strand match bases on the other strand (complementary).
• Two strands held together by hydrogen bonds.

DNA Structure and Function

• DNA is deoxyribonucleic acid, the genetic material.
• DNA has a double helix structure consisting of nucleotides with sugar, phosphate and nitrogenous bases.
• Chargaff's Rule: equal ratios of guanine/cytosine and adenine/thymine.

Central Dogma

• DNA replication makes a copy of DNA
• Following replication transcription takes the DNA information and makes RNA.
• Following transcription the information in RNA is translated into proteins.
• Replication, transcription, and translation

Amino Acids

• Proteins are composed of amino acids
• There are 20 amino acids.
• Amino acids differ in their side groups.

Probability

• Probabilities of events add up to 1.
• Mutually exclusive events are those that cannot occur at the same time.
• Independent events do not affect each other's probabilities.

Gregor Mendel

• Mendel’s 5 innovations
• Used pure breeding strains
• Used replicate, reciprocal, and test crosses
• Used controlled crosses between plants
• Studied dichotomous traits
• Quantified results

Meiosis

• The study of how/why genes are segregated into daughter nuclei.
• The physical basis is in the first division of meiosis the homologous chromosomes with their different versions of each gene are segregated into daughter nuclei.

Autosomal Inheritance

• Traits passed through autosomes (chromosomes other than sex chromosomes)
• Dominant inheritance: at least one affected parent, males and females affected equally
• Recessive inheritance: affected children born to unaffected parents, risk to subsequent children 1/4

Pedigrees

• Family trees are used to trace inheritance patterns in humans and some animals.
• Notation shows relationships, affected individuals

Chromosomes

• Genes are located on chromosomes
• A diploid cell contains two homologous copies of each chromosome
• Homologous chromosomes have the same genes in the same location
• During meiosis, an egg/sperm each contain 1 copy of each chromosome (haploid)
• Zygotes are formed during fertilization, a diploid cell (two copies of each chromosome)

Cell Division

• Mitosis: produces two identical diploid daughter cells
• Non-reproductive cells (somatic cells) undergo mitosis
• Meiosis: produces four haploid gamete cells, different from parent cells
• Reproductive cells (germ cells) undergo meiosis

Cell Cycle

• G1 phase: cell growth and activity
• S phase: DNA replication
• G2 phase: preparation for cell division
• M phase: cell division (mitosis or meiosis)

Mitosis vs. Meiosis

• Mitosis produces 2 identical diploid cells (1 cell division)
• Meiosis produces 4 haploid cells (2 cell divisions)

Gene Interaction

• Dominance relations between genes have molecular basis
• Gene expression affected by gene interaction
• Characteristic changes in Mendelian ratios
• Mutations in different genes can produce the same phenotype
• Complementation tests determine the number of genes causing a mutation

Molecular Basis of Dominance

• The dominance and recessiveness of an allele has a phenotypic basis (activity of the proteins the allele produces).

Recessive Mutations

• Loss-of-function mutation: gene loses its normal function.
• Hypomorphic mutations—functions lost, but partially
• Null mutations—functions completely lost

Fully Dominant Mutations

• Normal allele is usually haplosufficient, meaning a copy is required to produce the wild type.

Effects of Mutation

• Gain-of-function mutation—new function/increased activity
• Loss-of-function mutation—decreased/lost functionality of a gene/protein

Incomplete Dominance vs. Codominance

• Incomplete dominance: heterozygote is intermediate phenotype (mixture of homozygotes).
• Codominance: both alleles fully expressed in heterozygote (both traits are visible).

The C Gene System of Mammalian Coat Color

• The C gene is responsible for mammalian coat color
• It produces an enzyme active in melanin production
• Order of dominance among C gene alleles: C > cch > cch > c

Complementation Tests

• Complementation: if mutations are in the different genes, the wild-type phenotype is observed.
• No Complementation: if mutations are in the same gene, there is no wild-type phenotype.

Gene Interaction: Epistatic Interactions

• Epistatic interactions—2+ genes affect a trait.
• Leathal allele—can lead to death if inherited.
• Pleiotropy—one allele affects multiple phenotypes

Other Types of Gene Interactions

• Duplicate—multiple genes can have the same result
• Dominant epistasis—dominant allele from one gene masks expression from another gene
• Recessive epistasis—recessive allele at one locus masks alleles at a second locus
• Dominant suppression—one dominant allele suppressing a dominant allele of another gene

Studying Gene Interactions

• Find two mutants affecting the same phenotype (i.e., a trait).
• Do a complementation test to determine if two genes are involved.
• If genes are involved, perform dihybrid crosses and analyze offspring ratios to determine the interactions between the two implicated genes

Genetic Linkage and Mapping

• Genes located close together on the same chromosome are linked and do not follow the laws of independent assortment
• Chromosome theory of inheritance, genetic linkage, and chromosomal mapping.

Linked Genes Do Not Assort Independent

• Syntenic genes: genes on the same chromosome
• Genetic linkage: Linked genes do not follow the law of independent assortment; they tend to be inherited together more often than expected.
• Recombination: allele shuffling during crossing over. Nonrecombinants are similar to original alleles.

Independent Assortment of Syntenic Genes

• Genes far apart on chromosome segregate independently.
• Crossing over prevents linked genes from segregating.

Observations About Genetic Linkage

• Linked genes are always syntenic.
• Crossing over is less likely between linked genes that are far apart.

Conserved vs. Disrupted Synteny

• Conserved Synteny: similar genetic structures/gene order in different species
• Disrupted Synteny: genetic structure/gene order differs between different species.

Conserved vs. Disrupted Linkage

• Conserved linkage: syntenic and gene order of homologous genes maintained among species.
• Disrupted linkage: difference in gene order between species.

Types of Chromosome Fragments

• Chromosome Inversion: small blocks of genes get flipped around.
• Reciprocal Translocation: novel chromosomes are created.

Indications of Genetic Linkage

• Genetic linkage analysis compares observed and expected frequencies of gametes or progeny phenotypes
• Linked genes show higher frequency for parental allele combos than nonparental

Independent Assortment in Meiosis

• Independent assortment of genes that are NOT linked.
• Genes on the same chromosome do not assort independently.

Genetic Recombination

• Recombination: the natural process of breaking and rejoining DNA strands to generate genetic variation
• Homologous recombination: exchange of DNA segments between homologous chromosomes during meiosis.
• Crossing over: breakage and reunion leads to the exchange of chromosome parts between homologs.
• Complete genetic linkage: no crossing over, only parental gametes are produced.
• Incomplete genetic linkage: mixture of parental and nonparental gametes are produced

Linkage Analysis

• Linkage analysis tests for linkage/independent assortment of genes,
• Measures distance between linked genes
• Crossover frequency measures distance between genes on a chromosomes; more frequent crossovers indicate greater distance
• Genetic distance = recombination frequency × 100

Distance Between Genes

• Genetic map distances are additive

Determining Gene Order

• Three-point testcross: mapping three genes in a cross between a triple heterozygote and a triple recessive homozygote.
• Order of the genes determined by analyzing the number of recombinants and double recombinants

Null Hypothesis

• Null hypothesis (Ho): default position in a scientific analysis.
• States no significant difference or association between variables.
• There is no association; no effect of factor X on Y; no gene linkage; no evolution

Alternative Hypothesis

• Opposite of the null hypothesis
• States significant difference or association between variables.

Pearson’s Chi-Squared Test

• Summarizes observed data into a single value
• Measures how well observed offspring numbers fit the expected numbers

Goodness of Fit

• Chi-squared test statistic's distribution is consistent with null hypothesis

Degrees of Freedom

• Number of categories − 1= degrees of freedom

Chi-square analysis of Mendel's Data

• Interpretation of chi-square results based on the corresponding p-value.
• Degrees of freedom and critical value needed to determine statistical significance (p<0.05)

Chi-square (X²) test Steps

• Step 1: identify the null and alternative hypotheses
• Step 2: collect observed offspring data
• Step 3: determine expected offspring counts under the null hypothesis
• Step 4: calculate X^2 statistic using observed and expected data
• Step 5: calculate the degrees of freedom based on number of categories and associated parameters (population size and/or genetic characteristics).
• Step 6: match X^2 and degrees of freedom to p-value

Genetic Polymorphism

• Population’s gene pool: set of alleles it carries
• Genotype frequency: relative number of each genotype in population
• Allele frequency: relative number of each allele in population

Hardy-Weinberg Equilibrium

• The allele (and genotype) frequencies in a population will remain constant from one generation to the following, assuming certain conditions
• Asserts that allele (and genotype) frequencies remain constant in the absence of specific forces (mutation, selection, gene flow, and nonrandom mating) acting on the populace

Heterozygote Advantage

• In cases of balancing selection, the heterozygote has a higher fitness compared to either homozygote individuals.
• Example—sickle cell hemoglobin with malaria or sheep with horn variation.

Differential Reproduction and Relative Fitness

• Differential reproduction: differences in reproduction rates among phenotypes.
• Relative fitness (w): the reproductive success of a genotype relative to the most successful genotype.
• Selection coefficient (s): measure of the selective disadvantage of a genotype

Modeling Selection

• Modeling selection affects genes in a population by considering assumptions (Hardy-Weinberg Equilibrium, single locus and alleles, discrete generations, varying genotype fitness (relative fitness),

Allele Fitness

• wA = fitness of allele A, given by the frequencies of each genotype (AA, Aa, aa)
• The average fitness of the population is calculate based on combined frequency of genotypes and individual alleles

Modeling Directional Selection

• Step 1: Calculate surviving number of organisms (of each genotype)
• Step 2a: determine allele frequencies after selection
• Step 2b: determine genotype frequencies in the next generation; based on the new allele frequencies
• Natural selection: drift in allele and genotype frequencies, allele fixation.

Modeling Heterozygote Advantage

• Shows that heterozygotes are more fit than one type of homozygous genotype in population.
• Genotype fitness (w) calculated to understand allele frequencies over time.

Stable Equilibrium

• In balance between mutation and selection, a population maintains equal rates of loss of and gain of variation.
• H, calculates the equilibrium frequency based on the mutation rate and selective coefficients

Genetic Drift

• Results from random fluctuations in allele frequencies in small populations; loss/gain of traits

The Founder Effect

• A reduction in genetic diversity when a small population breaks away from a larger population.
• Can lead to changes in allele frequencies

Genetic Bottlenecks

• A reduction in genetic diversity in a population due to a catastrophic event (not selection)
• Reduces the population size, lowers genetic diversity, increases potential for inbreeding and reduced fitness

Genetic Drift and Population Size

• The impact of genetic drift increases with the decrease in population size.

The Wahlund Effect

• Reduction in heterozygosity (loss of genetic variation) can occur as a consequence of genetic variation among subpopulations from a more diverse larger main population.

Non-Random Mating

• Nonrandom mating—probability that two individuals in a population will mate is not the same for all possible pairs. These matings include assortative mating (preference for similar traits), inbreeding (mating with relatives), or outbreeding.

Identity by Descent (IBD)

• Identifies situations where genes in organisms are derived from the same ancestral gene.

Calculating IBD Pedigrees

• Calculating the probability that alleles are IBD based on pedigree structures

Features of Hereditary Material

• Features for hereditary material include locality and function(replication, storage, expression).
• DNA is organized into a double helix with specific base pairings.

DNA Forms and Characteristics

• DNA forms: A-DNA, B-DNA, Z-DNA
• Properties of A-DNA, B-DNA, and Z-DNA

Chargaff's Rule

• Rule of bases in DNA—certain ratios of bases (guanine–cytosine, adenine–thymine)

DNA Replication

• Mechanisms of DNA Replication, steps, and methods
• Meselson-Stahl Experiment: demonstrated the semi-conservative model.

Replication Initiation

• DNA replication initiating enzymes bind to OriC (consensus) sequences, attracting other replication enzymes.
• DnaA binds to DNA, breaking hydrogen bonds and generating an open complex
• DnaC delivers DnaB protein to open complex to begin helicase activity.

DNA Replication Rules

• DNA is synthesized from 5' to 3'.
• Unwinding and synthesis must be coordinated

DNA Replication Steps in bacteria

• Steps in bacterial DNA replication include initiation, elongation, and termination.
• Leading strand synthesis is continuous, whereas lagging strand synthesis is discontinuous.
• Short segments in lagging strand called Okazaki fragments are joined by ligase

Eukaryotic DNA Polymerases

• Eukaryotic DNA replication uses a greater amount and types of DNA polymerases compared to prokaryotes

DNA Proofreading

• DNA polymerases have 3' to 5' exonuclease activity to remove mismatched nucleotides.

Finishing Replication

• Telomeres: repeated sequences at the ends of linear chromosomes to prevent loss.
• Telomerase: enzyme that synthesizes telomeres.

Mutations

• Mutations are changes in the DNA itself
• Types and frequencies of mutations, chemical and/or radiation-induced

Base-pair Substitution Mutations

• Transition—purine to purine or pyrimidine to pyrimidine
• Transversion—purine to pyrimidine or pyrimidine to purine
• Silent—no amino acid change, missense—amino acid change, nonsense—premature stop codon, frameshift—insertion or deletion causing shift in reading frame.

Regulatory mutations

• Examples of regulatory mutations that affect splicing, and protein quantity (but not sequence).

Types of Radiation

• Damage to genetic material due to various forms of radiation

The Ames Test

• In vitro test that measures mutagenicity of substances.
• Tests how likely a substance will cause mutations.

Direct Repair of DNA Damage

• Repair of Thymine dimers through nucleotide excision repair and photoreactivation
• Mismatch repair enzymes distinguish between original and new nucleotide.

Genetic Testing

• Medical tests that identify changes in chromosomes, genes, or proteins
• Types of tests: molecular, chromosomal, and biochemical.
• Uses examples for each of the types (newborns, diagnostic, carriers, prenatal, predictive, forensic)

Methods for genetic testing

• Study of single genes/short lengths of DNA.
• Analysis of whole chromosomes.
• Study of protein activity.

Epigenetics

• Study of heritable changes in gene expression that don't involve changes in DNA sequence.
• Influenced by factors like age, lifestyle, and environment; can lead to diseases like cancer.
• 3 mechanisms: DNA methylation, histone modification, ncRNA-associated gene silencing.
• Epigenetics/environment interplay—factors like prenatal exposure (famine) influence adult disease risk.

Twins

• Study of similarities/differences between monozygotic and dizygotic twins to differentiate whether a disease/trait is more influenced by genetic or environmental factors

Test your knowledge on key concepts related to cell division, meiosis, and molecular genetics. This quiz covers topics such as the roles of sister chromatids, DNA replication, and protein synthesis, along with fundamental principles of evolution. Challenge yourself to understand the intricacies of these biological processes.