General Biology (Bio107)

Chapter 8-2

– Sexual Reproduction& Meiosis -

• Reproduction is one of the hallmark characteristics of all forms of life on planet Earth; all living organisms reproduce

• During reproduction they hand over (= inherit) their individual genetic make-up and information over to a next generation

• The transmission of traits from one generation to the next is called heredity or inheritance.

• Reproduction assures the continuation of a species over time

• Reproduction means the formation of a new organism from a pre-existing one - for most organisms the new individual starts with a fertilized egg in a process called fertilization

Reproduction & Role of meiosis

• Three major forms of reproduction are established in the living world.1. Sexual reproduction - predominant form of reproduction in multi-cellular eukaryotes and animals - fusion of a haploid egg cell and one haploid sperm forms diploid zygote which starts a new individual2. Asexual reproduction - type of reproduction mostly found in bacteria and amoeba - e.g. bacteria reproduce in process called ‘binary fission’ - DNA of the offspring is inherited from one parent or cell and is identical with parental DNA3. Parthenogenesis - rare form of reproduction is performed by certain amphibians and reptiles - e.g. whiptail lizard

Types of Reproduction

Common observations with sexual reproduction:1. Offspring resemble their parents more than they do less closely related individuals of the same species2. Offspring differ somewhat from parents and siblings, demonstrating variation.3. Parents endow their offspring with coded information in the form of genes4. Offspring of sexual reproduction vary genetically from their siblings and from both parents.

Alternation of haploid (1n) and diploid (2n)stages in the human life cycle

GametesGametes(1n)(1n)

ZygoteZygote(2n)(2n)

GonadsGonads

TestisTestis

OvariesOvaries

Sperm

Oocyte(egg cell)

23 chromosomes23 chromosomes(= 1n)(= 1n)

23 chromosomes23 chromosomes(= 1n)(= 1n)

Genes• Genes program specific traits that emerge as we develop from fertilized eggs into adults

• Genes are segments of DNA

• Genetic information is transmitted as specific sequences of the four deoxyribonucleotides in DNA

• Cells translate genetic “sentences” (= nucleotide sequences) into traits and other features with no resemblance to genes

• Most genes program cells to synthesize specific enzymes and other proteins that produce an organism’s inherited traits.

Chromosomes

• Almost all of the DNA in a eukaryotic cells is subdivided into chromosomes in the nucleus.– Tiny amounts of DNA are found in mitochondria

and chloroplasts• Every living species has

a characteristic number of chromosomes.– Humans have 46 chromosomes

• Each chromosome consists of single DNA molecule in association with various proteins.

• Each chromosome has hundredsor thousands of genes, each at a specific location, it’s locus.

• Sets of paternal and maternal chromosomes form the homologous chromosome pairs• The complete set of chromosomes of an organism is called the diploid number

Chromosome Sets

Sex orgenderchromosomes

Chr #1 – 22:Autosomes

• Early during embryogenesis, haploid gametes are formed by specialized cells, the primordial germ line cells, by a unique form of cell division called meiosis

• Meiosis involves reduction of the genetic material from a double (= diploid, 2n) chromosomal set to a single (= haploid, 1n) set

• Meiosis comprises two successive nuclear divisions with only one round of DNA replication

• Meiosis creates: 1. Haploid germ cells (eggs and sperm) from a diploid parent cell

2. Increased genetic variety due to crossing over events

Gamete formation & Role of meiosis

The two cell division phases of meiosis

FSH

stimulates

One PrimordialGerm cell (2n)

In gonads

4 Gametes (1n)

• Meiosis reduces chromosome number by copying the chromosomes once, but dividing twice.

• The first division, meiosis I, separates homologous chromosomes.

• The second, meiosis II, separates sister chromatids.

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

• Division in meiosis I occurs in four phases: prophase, metaphase, anaphase, and telophase.

• During the preceding interphase the chromosomes are replicated to form sister chromatids.– These are genetically identical

and joined at the centromere.• Also, the single centrosome

is replicated.

Interphase

• In prophase I, the chromosomes condense and homologous chromosomes pair up to form tetrads.– In a process called synapsis, special proteins

attach homologous chromosomes tightly together.– At several sites the chromatids of

homologous chromosomes are crossed (chiasmata) and segments of the chromosomes are traded.

– A spindle forms from each centrosome and spindle fibers attached to kinetochores on the chromosomes begin to move the tetrads around.

Prophase I

maternal

paternal

allelea b c

a b c

a b c

a b c

New allele combinations due to crossing over in Prophase I

EM Image

• At metaphase I, the tetrads are all arranged at the (virtual) metaphase plate.– Microtubules from one pole are attached to the

kinetochore of one chromosome of each tetrad, while those from the other pole are attached to the other.

• In anaphase I, the homologous chromosomes separate and are pulled toward opposite poles.

Metaphase I

Random alignment of homologous chromosomes in Metaphase IRandom alignment of homologous chromosomes in Metaphase I

Haploid number n = 3

DNA-replicationDNA-replication

oror

or or or oror

or

Prophase IProphase I

8 different8 differentMetaphase IMetaphase IAlignmentsAlignmentsare possibleare possible

with 6 chromosomeswith 6 chromosomes

Ncomb = 2n

General:

For this example:

Ncomb = 23 = 8

• In telophase I, movement of homologous chromosomes continues until there is a haploid set at each pole.– Each chromosome consists of linked sister

chromatids.• Cytokinesis by the same

mechanisms as mitosis usually occurs simultaneously.

• In some species, nuclei may reform, but there is no further replication of chromosomes.

Telophase I & Cytokinesis I

• Meiosis II is very similar to mitosis, but no DNA replication takes place at the beginning of meiosis II– During prophase II a spindle apparatus forms,

attaches to kinetochores of each sister chromatids, and moves them towards themetaphase plate.• Spindle fibers from one pole

attach to the kinetochore of one sister chromatid and those of the other pole to the other sister chromatid.

Prophase II

• At metaphase II, the sister chromatids are arranged at the (virtual) metaphase plate.– The kinetochores of sister

chromatids face opposite poles.

• At anaphase II, the centomeres of sister chromatids separate and the now separate sisters travel toward opposite poles.

Metaphase II & Anaphase II

• In telophase II, separated sister chromatids arrive at opposite poles.– Nuclei form around

the chromatids.• Cytokinesis II separates

the cytoplasm.

• At the end of meiosis, there are four haploid daughter cells which aregenetically different

Telophase II & Cytokinesis II

• Mitosis produces two identical daughter cells, but meiosis produces 4 very different cells.

Diploid (2n)Diploid (2n)Gamete mother cell

DNA-replication

Tetrad formation &Crossing over

Homologous chromosomessegregate

Sister chromatidsseparate

Haploid (1n)Haploid (1n)Gametes (sperm or oocytes)

Prophase I

Metaphase I

Anaphase I

Random alignmentof homologous chromosomes

Prophase II

Anaphase II

Activationby FSH

• Meiosis consists of many intricate steps, involving many enzymes and protein components• It is a highly vulnerable cellular process prone to errors • Errors which affect the symmetric separation of chromosomes during meiosis I or II lead to alterations of chromosome numbers or chromosomal aberrations• Following accidents during meiosis leading to alterations of chromosome numbers are:1. Non-disjunction in meiosis I homologous chromosome pairs fail to separate during Metaphase I of meiosis n+1 or n-1 gametes form at the end of meiosis2. Non-disjunction in meiosis II sister chromatids fail to separate during Metaphase II n, n+1 or n-1 gametes form at the end of meiosis

Meiosis & Non-disjunction events

Inter-Inter-phasephase

Pro-Pro-phase Iphase I Meta-Meta-

phase Iphase I

Pro-Pro-phase IIphase II

Meta-Meta-phase IIphase II

n+1 or n-1n+1 or n-1GametesGametes

DisturbingDisturbingFactorFactor

Graphic©E.Schmid/2001

Aberrant chromosome numbers in gametes due to Non-disjunction event in meiosis I

Inter-Inter-phasephase

Pro-Pro-phase Iphase I Meta-Meta-

phase Iphase I

Pro-Pro-phase IIphase II

Meta-Meta-phase IIphase II

n, n+1 or n-1n, n+1 or n-1GametesGametes

DisturbingDisturbingFactorFactor

Graphic©E.Schmid/SWC2001 Normal

Aberrant

Aberrant chromosome numbers in gametes due to Non-disjunction event in meiosis II

Fertilization involving gametes with wrong (= aberrant) chromosome numbers or chromosome patterns results in offspring with chromosomal abnormalities, = additional/extra or missing chromosomes in the resulting zygote and embryo

The most common chromosomal aberrations in humans are:1. Trisomies - cells have extra chromosome2. Monosomies - cells are missing one chromosome

• Severe chromosomal aberrations or defects in an individual or embyo can be early detected and analyzed by preparing a so-called karyogram

• Karyotypes, ordered displays of an individual’s chromosomes, are often prepared with lymphocytes.

Chromosomal aberration & Karyotype analysis

Normal Karyogram

A typical karyotype analysis involves comparing chromosomes for their:

1. Number (e.g. Trisomies)2. Length (e.g. deletions, translocations)3. Placement of centromeres4. Location and sizes of chromosomal G-bands

(deletions, insertions, inversions) the Giemsa dye stains regions of chromosomes that

are rich in the base pairs Adenine (A) and Thymine (T) where it produces the typical dark bands, the G-bands

Human chromosome pair

1 2 3 4 5 6 7

8 9 10 11 12 13 14 15

16 17 18 19 20 XX21 22

Normal karyogram of a human female

Chr. 1 Chr. 1 22 = Autosomes 22 = Autosomes

Sex Sex chromosomeschromosomes

1. Trisomy 21 (= Down syndrome)- Cells show extra copy of the chromosome 21 in a karyogram- Together with Trisomy 13 - the most common chromosome number abnormality in humans- Affects about 1 out of every 700 children born in the US- Affected people suffer from heart defects, susceptibility to respiratory infections, leukemia; have a shorter life-span- Many affected individuals exhibit varying degrees of mental retardation- Incidence of Down syndrome in the offspring of genetically normal parents increases markedly with the age of the mother (> 35 y old)- The chromosome alterations of Trisomy 21 are suspected to occur after fertilization

Genetic disorders in humans caused by chromosomal aberrations

Trisomy 21 Karyogram

2. Trisomy 13 (Pateu’s syndrome)- Affected human individuals are characterized by cells which show an extra copy of the chromosome 13 in a karyogram- Chromosomal aberration is observed in about 1/5000 life births- Trisomy 13 babies are frequently stillborn or die as newborns- Physical abnormalities include: severe mental retardation, growth retardation, mis-development of the brain/spinal cord, cleft lip and palate, cyclopia (one eye) often with protruding facial proboscis

Trisomy 13 Karyogram

Examples of clinical features of Trisomy 13:

• Non-disjunction events affecting sex chromsosomes - have usually less dramatic effects on the genetic balance and on phenotype of the carrier probably due to lesser number of genes on sex chromosomes and natural inactivation of the second X-chromosome in an XX (= female) individual• The most common sex chromosome abnormalities are:1. Extra Y chromosome (XYY)

- Observed in 1/2500 live births- Affected males have larger body stature and borderline intelligence- New studies give hints to mild to severe social behavioral disturbances with trend to accumulated criminal records

2. XXY = Klinefelter syndrome)- Cells of human males show an extra X chromosome - Observed in 1/2000 live births- Affected males have abnormally small testes & sterility- Often accompanied by breast enlargement

Chromosomal aberrations of sex chromosomes

3. XXX = Multi-X female (“super-female”)- Carriers have limited fertility- Around 1 in 1000 woman has three or more X-chromosomes- Most 47,XXX women are phenotypically ‘normal’- 48,XXXX woman are usually mildly retarded, and 49,XXXXX produces severe disability

4. XO = Turner syndrome- Affected individuals are females - Show underdeveloped ovaries, poor breast development and a so-called “web of skin” between neck and shoulders- Carriers are sterile

Chromosomal aberrations of sex chromosomes

• More subtle changes in chromosome structures and shapes can be caused by a series of other factors, such as strong irradiation (e.g. X-rays, radioactivity) and environmental factors (e.g. toxins, viruses).

• Events which lead to abnormal chromosomal structures are:

1. Deletions- A chromosomal piece breaks off and gets lostChromosome 5p deletion syndrome or (“cat cry syndrome”)

- caused by deletion of the short (= p) arm of the human Chr # 5 - affects 1/20,000 to 1/50,000 human life births - infants with cri du chat syndrome commonly have a distinctive

cat-like cry - show severe mental retardation,

low birth weight, microcephaly, webbed fingers or toes

Chromosome 13q deletion - common finding in human blood cancers, such as: B-cell chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma

Other Chromosomal Changes