UNIT 4 Chapter 12: The Cell Cycle Chapter 13: Meiosis & Sexual Life Cycles Chapter 14: Mendel & The Gene Idea Chapter 15: The Chromosomal Basis of Inheritance.

UNIT 4Chapter 12: The Cell Cycle

Chapter 13: Meiosis & Sexual Life CyclesChapter 14: Mendel & The Gene Idea

Chapter 15: The Chromosomal Basis of Inheritance

Chapter 16: The Molecular Basis of Inheritance

Introduction to Cell Division

• The cell cycle propagates a lineage of cells• The cell theory

• DNA exists in the nucleus as chromatin• Chromatin = DNA + histone proteins

• DNA wound around histones = nucleosomes

• Chromatin is arranged into discrete structures called chromosomes

• Eukaryotes all possess a characteristic number of chromosomes

• During cell division, each chromosome is duplicated and held to its copy by the centromere• Each half called a

sister chromatid• Chromatids are

eventually separated into different cells

Types of Division

• All cells undergo division at some point in their life cycle• Somatic cells: mitosis = 2 daughter cells identical

to 1 parent cell• 46 chromosomes (human)

• Gametes (sex cells): meiosis = 4 daughter cells unique to each other and 1 parent cell

• 23 chromosomes (human)

• Cytokinesis is the division of the cell itself

Mitosis

• Mitotic phase (M) alternates with interphase• 90% of cell’s life spent in interphase

• G1 = growth, daily activities

• S = DNA synthesis

• G2 = finalizes preparation for division

• M = division of nucleus

• Mitosis is a 4 step process• Prophase• Metaphase• Anaphase• Telophase

• After mitosis, cells may undergo division again, or enter the G0 phase

Mitosis - Prophase

• Chromosomes have duplicated and centrosomes begin forming spindle fibers as they move to the poles of the cell• Spindle fibers which push on one another to move

mitotic spindle

• Nuclear envelope fragments and some spindle fibers interact with kinetochores

• Other spindle fibers attach to spindle fibers from opposite pole

Mitosis - Metaphase

• Spindle fibers move the chromosomes until they reach the metaphase plate• Imaginary plane equidistant between the poles

Mitosis - Anaphase

• Centromeres divide, separating the sister chromatids• Chromatids (now chromosomes) “walk” along

spindle fiber, moving closer to pole

• Ultimately, each pole has an equivalent collection of chromosomes

Mitosis - Telophase

• Cell continues to elongate

• Fragments of the original nuclear membrane are used to begin forming two new nuclei

• Kinetochore spindle fibers disconnect from chromosomes and cytokinesis begins

Cytokinesis

• Cytokinesis follows mitosis• Animals: cleavage furrow

forms• Plants: cell plate forms

Regulation of the Cell Cycle

• The frequency of cell division depends mainly on the cell type

• Events in the cell cycle are controlled by a cell cycle control system• Checkpoints are control

points• Cyclins are proteins

involved with regulation

• Growth factors are important in density-dependent inhibition

• Most animal cells exhibit anchorage dependence

• Cancer cells have escaped the cell cycle• Do not exhibit density-

dependent inhibition or anchorage dependence

• If, and when, cancer cells stop dividing, they do so at random points, not at the typical checkpoints

• Most cells divide up to 50 times before they senesce• HeLa cells

• Transformation occurs when a normal cell in a tissue becomes cancerous• Immune system normally destroys these cells• Cells that escape destruction continue to divide to

form a tumor• Benign

• Malignant

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Offspring Receive Genetic Material from ParentsOffspring Receive Genetic Material from Parents

DNA (or chromosomes) is transmitted to offspring via gametes

Sperm & egg are haploidFertilization is the union of sperm and egg

Most human cells possess 46 chromosomes - diploid

Sequences of DNA, genes, exist on chromosomes to direct production of proteins

• Genes exist at a locus, or location on a chromosome

Meiosis Reduces Chromosome NumberMeiosis Reduces Chromosome Number

Meiosis goal: to reduce diploid cells into haploid onesMeiosis resembles mitosis, but how genetic material is segregated differs

Two cell divisions: Meiosis I and Meiosis II

Prophase IProphase I

Homologous pairs line up to form tetradsSynapsis (crossing over) involves the swap of genetic material between non-sister chromatids

Non-sister chromatids are crossed at chiasmata

Metaphase I & Anaphase IMetaphase I & Anaphase I

Tetrads line up at metaphase plate and the homologous pairs are separated, but sister chromatids remain attached

Metaphase II & Anaphase IIMetaphase II & Anaphase II

The sister chromatids line up at metaphase plate and the chromatids are segregated to the opposite poles

Sexual Life Cycles Produce Offspring VariationSexual Life Cycles Produce Offspring Variation

Three main reasons for variation exist:Crossing overRandom fertilizationIndependent assortment

Crossing over produces recombinant chromosomes, new combinations of genetic material that doesn’t exist in either parentIndependent assortment

Adding random fertilization and independent assortment can produce over 70 trillion chromosome combinations

Crossing over adds even more possibilities!… plus, the chance of mutation.

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• Mendel cross-pollinated (Mendel cross-pollinated (hybridizehybridize) two ) two contrasting, contrasting, true-breedingtrue-breeding pea varieties pea varieties– True-breeding parents are the True-breeding parents are the P P

generationgeneration and their hybrid offspring are and their hybrid offspring are the the FF11 generation generation

• Mendel would then allow the FMendel would then allow the F11 hybrids hybrids

to pollinate to produce an Fto pollinate to produce an F22 generation generation

• FF22 plants revealed two fundamental plants revealed two fundamental

principles of heredity:principles of heredity:– law of segregationlaw of segregation– law of independent assortmentlaw of independent assortment

•A description of an organism’s traits is its A description of an organism’s traits is its phenotypephenotype•A description of its genetic makeup is its A description of its genetic makeup is its genotypegenotype

Law of segregationLaw of segregation

• P generation true-breeders produced all of the P generation true-breeders produced all of the same phenotype, same phenotype, as seen in one of the P gen. parents as seen in one of the P gen. parents

• When FWhen F11 plants pollinated, the F plants pollinated, the F22

generation included both generation included both phenotypes seen in the P gen.phenotypes seen in the P gen.

• Ex. Mendel Ex. Mendel recorded 705 recorded 705 purple-flowered Fpurple-flowered F22

plants and 224 plants and 224 white-flowered Fwhite-flowered F22

plants from the plants from the original crossoriginal cross– 3:1 ratio3:1 ratio

• Law of segregation has four parts:Law of segregation has four parts:

1. 1. Alternative version of genes, called Alternative version of genes, called allelesalleles, account for variations in inherited , account for variations in inherited characterscharacters

• Different alleles vary in the sequence of Different alleles vary in the sequence of nucleotides at the locus of a genenucleotides at the locus of a gene

2. 2. For each character, an organism inherits two For each character, an organism inherits two alleles, one from each parentalleles, one from each parent– Diploid (2n) organism inherits one set of chromosomes Diploid (2n) organism inherits one set of chromosomes

from each parentfrom each parent

– Organism has a pair of homologous chromosomes Organism has a pair of homologous chromosomes and therefore two copies of each locusand therefore two copies of each locus

3. 3. If two alleles differ, then the If two alleles differ, then the dominant alleledominant allele is is fully expressed in the organism’s appearancefully expressed in the organism’s appearance– Recessive alleleRecessive allele has no noticeable effect on the has no noticeable effect on the

organism’s appearanceorganism’s appearance

4. The 4. The two alleles for each character segregate two alleles for each character segregate (separate) during gamete production(separate) during gamete production

• If an organism has identical alleles (If an organism has identical alleles (homozygoushomozygous) ) for a particular character, then 100% of gametes for a particular character, then 100% of gametes produced will gain that alleleproduced will gain that allele

• If different alleles (If different alleles (heterozygousheterozygous) are present, then ) are present, then 50% of the gametes will receive one allele and 50% 50% of the gametes will receive one allele and 50% will receive the otherwill receive the other

Alleles Segregate into Gametes Alleles Segregate into Gametes IndependentlyIndependently

• Experiments that study only a single character Experiments that study only a single character are called are called monohybridmonohybrid crosses crosses– Two different characters = a Two different characters = a dihybriddihybrid cross cross

The relationship between genotype and The relationship between genotype and phenotype is rarely simplephenotype is rarely simple

• Some characters reflect Some characters reflect incomplete dominanceincomplete dominance where heterozygotes where heterozygotes show a distinct show a distinct intermediate (blended) intermediate (blended) phenotypephenotype

• CodominanceCodominance involves two alleles which affect involves two alleles which affect the phenotype individuallythe phenotype individually– Ex. Human blood typesEx. Human blood types

• Dominance/recessiveness relationships have Dominance/recessiveness relationships have three important points:three important points:

1. They range from complete dominance, though degrees 1. They range from complete dominance, though degrees of incomplete dominance, to codominanceof incomplete dominance, to codominance

2. They do not involve the ability of one allele to subdue 2. They do not involve the ability of one allele to subdue another at the level of DNAanother at the level of DNA

3. They do not tell how common a trait is in a population3. They do not tell how common a trait is in a population

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Variation & Genetic Mapping

• Offspring with new combinations of traits inherited Offspring with new combinations of traits inherited from two parents is from two parents is genetic recombinationgenetic recombination

• Genetic recombination can result from: independent Genetic recombination can result from: independent assortment or from crossing overassortment or from crossing over

• Frequency of crossing over data used for Frequency of crossing over data used for constructing a constructing a chromosome mapchromosome map• Map is an ordered list of the genetic loci along a particular Map is an ordered list of the genetic loci along a particular

chromosomechromosome

• Frequency of recombinant offspring reflects the Frequency of recombinant offspring reflects the distances between genes on a chromosomedistances between genes on a chromosome• Genes far apart = higher probability that crossover will occur Genes far apart = higher probability that crossover will occur

between thembetween them

• The distance between genes, the recombination The distance between genes, the recombination frequency, are called frequency, are called map unitsmap units• 1 map unit = 1% crossover frequency1 map unit = 1% crossover frequency

• Recombination frequencies are not always additive: Recombination frequencies are not always additive: 9% (b-cn) + 9.5% (cn-vg) 9% (b-cn) + 9.5% (cn-vg) ≠≠ 17% (b-vg). 17% (b-vg).• Second crossing over can “cancel out” the first Second crossing over can “cancel out” the first • Genes father apart are more likely to experience multiple Genes father apart are more likely to experience multiple

crossing over eventscrossing over events

• Some genes on a chromosome are so far apart that a Some genes on a chromosome are so far apart that a crossover between them is virtually certaincrossover between them is virtually certain• Frequency of recombination reaches Frequency of recombination reaches 50%50% • Genes act as if found on separate chromosomesGenes act as if found on separate chromosomes

Chromosomes and Sex

• This X-Y system of mammals This X-Y system of mammals is not the only chromosomal is not the only chromosomal mechanism of determining sexmechanism of determining sex

• Other types include the X-0 Other types include the X-0 system, the Z-W system, and system, the Z-W system, and the haplo-diploid systemthe haplo-diploid system

• In humans, individuals with the In humans, individuals with the SRYSRY gene (on Y gene (on Y chromosome), the generic embryonic gonads are chromosome), the generic embryonic gonads are modified into testesmodified into testes• SRY gene activates a series of events to cause fetus to SRY gene activates a series of events to cause fetus to

develop as a maledevelop as a male• Genes on other chromosomes activatedGenes on other chromosomes activated

• Other genes on the Y chromosome are necessary for the Other genes on the Y chromosome are necessary for the production spermproduction sperm

• Lacking SRY? Default sex, female, developsLacking SRY? Default sex, female, develops• Sex-linked genes (and the sex chromosomes) have Sex-linked genes (and the sex chromosomes) have

unique patterns of inheritanceunique patterns of inheritance

Variation in Chromosomes

• NondisjunctionNondisjunction occurs when problems with the meiotic occurs when problems with the meiotic spindle cause errors in daughter cellsspindle cause errors in daughter cells• Tetrad chromosomes Tetrad chromosomes

do not separate do not separate properly during properly during meiosis Imeiosis I

• Sister Sister chromatids may fail chromatids may fail to separate during to separate during meiosis IImeiosis II

• Some gametes receive two of the same type of Some gametes receive two of the same type of chromosome and another gamete receives no copychromosome and another gamete receives no copy

• Cell with abnormal (too many OR too few) number of Cell with abnormal (too many OR too few) number of chromosomes= chromosomes= aneuploidaneuploid• TrisomicTrisomic cells = three copies of a particular chromosome cells = three copies of a particular chromosome

type and have 2n + 1 total chromosomestype and have 2n + 1 total chromosomes• MonosomicMonosomic cells = only one copy of a particular cells = only one copy of a particular

chromosome type and have 2n - 1 chromosomeschromosome type and have 2n - 1 chromosomes

• Organisms with more than two complete sets of Organisms with more than two complete sets of chromosomes, have undergone chromosomes, have undergone polyploidypolyploidy• Could be triploid (3n) or tetraploid (4n)Could be triploid (3n) or tetraploid (4n)• Polyploidy is not tolerated in some cell types or speciesPolyploidy is not tolerated in some cell types or species

• Chromosomal MutationsChromosomal Mutations• Four types of changes in chromosome structure:Four types of changes in chromosome structure:

• DeletionDeletion occurs when a chromosome fragment is lost occurs when a chromosome fragment is lost during cell divisionduring cell division

• Missing certain genesMissing certain genes

• DuplicationDuplication occurs when a fragment becomes attached occurs when a fragment becomes attached as an extra segment to a sister chromatidas an extra segment to a sister chromatid

• InversionInversion occurs when a chromosomal fragment reattaches occurs when a chromosomal fragment reattaches to the original chromosome but in the reverse orientationto the original chromosome but in the reverse orientation

• TranslocationTranslocation, a chromosomal fragment joins a , a chromosomal fragment joins a nonhomologous chromosomenonhomologous chromosome

• Some translocations are reciprocalSome translocations are reciprocal

Examples of Human Disorders

• Down SyndromeDown Syndrome: trisomy of chromosome 21 (1/700): trisomy of chromosome 21 (1/700)• Kleinfelter’s SyndromeKleinfelter’s Syndrome: XXY, anatomically male but : XXY, anatomically male but

sterile, may have some female characters (1/2000)sterile, may have some female characters (1/2000)• Trisomy XTrisomy X: XXX, normal females (1/2000): XXX, normal females (1/2000)• Turner’s SyndromeTurner’s Syndrome: X0, anatomically female, but : X0, anatomically female, but

immature (1/5000)immature (1/5000)

Extranuclear Genes

• Not all of a eukaryote cell’s genes are located Not all of a eukaryote cell’s genes are located in the nucleusin the nucleus

• Extranuclear genes are found in mitochondria Extranuclear genes are found in mitochondria and chloroplastsand chloroplasts• Not distributed to gametes during meiosisNot distributed to gametes during meiosis

• A zygote inherits all of its mitochondria only A zygote inherits all of its mitochondria only from the ovumfrom the ovum• Sperm provides only a haploid nucleusSperm provides only a haploid nucleus• Mitochondrial genes in mammals display maternal Mitochondrial genes in mammals display maternal

inheritanceinheritance

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Structure of DNAStructure of DNA

DNA is a polymer of DNA is a polymer of nucleotidesnucleotides– Sugar, phosphate, Sugar, phosphate,

nitrogenous basenitrogenous base Sugar and phosphate are Sugar and phosphate are

backbones, bases at the backbones, bases at the interiorinterior

(A)denine, (T)hymine, (A)denine, (T)hymine, (G)uanine, (C)ytosine(G)uanine, (C)ytosine

– Double-stranded in Double-stranded in twisted shape = twisted shape = double double helixhelix

Base pairingBase pairing rule: rule:– A with T, two hydrogen A with T, two hydrogen

bondsbonds– G with C, three hydrogen G with C, three hydrogen

bondsbonds Strands are Strands are anti-anti-

parallelparallel to one another to one another– 5’ phosphate and 3’ OH5’ phosphate and 3’ OH

DNA Replication: The Details …DNA Replication: The Details …

A human somatic cell can replicate its A human somatic cell can replicate its 3 billion base pairs within a few hours 3 billion base pairs within a few hours and only one error per billion and only one error per billion nucleotides!nucleotides!

More than a dozen enzymes and More than a dozen enzymes and proteins participate in DNA replicationproteins participate in DNA replication

Replication begins at numerous sites Replication begins at numerous sites called called origins of replicationorigins of replication– HelicaseHelicase first unwinds the double helix first unwinds the double helix– Single-stranded binding proteinsSingle-stranded binding proteins open open

and hold the strands apartand hold the strands apart

DNA strands separate forming a DNA strands separate forming a “bubble” and two “bubble” and two replication forksreplication forks

DNA polymerase III is primarily DNA polymerase III is primarily responsible for the addition of responsible for the addition of nucleotidesnucleotides– Approx. 50 nucleotides/secondApprox. 50 nucleotides/second

DNA polymerase III behaviorsDNA polymerase III behaviors– It can ONLY add nucleotides to a pre-It can ONLY add nucleotides to a pre-

existing strand of DNAexisting strand of DNA– It can ONLY add nucleotides to a 3’ OH (in It can ONLY add nucleotides to a 3’ OH (in

eukaryotes)eukaryotes) ““Solutions”Solutions”

– – PrimasePrimase base pairs base pairs about 10 RNA about 10 RNA nucleotides to nucleotides to the DNA the DNA

forming forming a a primerprimer

– The primer is The primer is removed by DNA removed by DNA Polymerase I and DNA Polymerase I and DNA nucleotides can be nucleotides can be added, closing the added, closing the gapgap

Only one strand of Only one strand of the parent DNA is the parent DNA is oriented properly 3’ oriented properly 3’ 5’ into the 5’ into the replication forkreplication fork– Leading strandLeading strand can can

add nucleotides add nucleotides continuouslycontinuously

– Lagging strandLagging strand must must replicate new DNA in replicate new DNA in pieces = pieces = Okazaki Okazaki fragmentsfragments Okazaki fragments are Okazaki fragments are

later joined to one later joined to one another by another by DNA ligaseDNA ligase

DNA Replication: A SummaryDNA Replication: A Summary

Leading strand is copied continuously Leading strand is copied continuously into the fork, while the lagginginto the fork, while the laggingstrand is copied away strand is copied away

from the fork in from the fork in segments, each segments, each requiring a primer requiring a primer

Telomeres & TelomeraseTelomeres & Telomerase

The ends of the The ends of the DNA molecule DNA molecule are replicated are replicated by a special by a special processprocess– The linear The linear

nature of nature of eukaryotic eukaryotic chromosomes chromosomes poses a problemposes a problem

TelomeresTelomeres protect genes from being protect genes from being eroded as DNA is replicatederoded as DNA is replicated– (Humans: TTAGGG repeated 100-1000 times)(Humans: TTAGGG repeated 100-1000 times)

Telomerase restores lost telomeric Telomerase restores lost telomeric sequencesequence– Provides space for primaseProvides space for primaseand DNA polymerase and DNA polymerase

to extend the 5’ to extend the 5’ endend Telomerase not active Telomerase not active

in somatic cellsin somatic cells– Telomerase ACTIVE in:Telomerase ACTIVE in:

Germ-line cellsGerm-line cells Stem cellsStem cells Cancer cellsCancer cells

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