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Genetics, Meiosis, and the
Molecular Basis of Heredity
Theories on Inheritance
• It was clear for millennia that offspring
resembled their parents, but how this
came about was unclear.
• Do males and females harbor
homunculi?
• Do the components of sperm and egg
mix like paint?
• What role do gametes and
chromosomes play?
Theories on Inheritance
• Genetics = the science of heredity
• This section will focus on the molecular
mechanisms of genetics
Genetics, Meiosis, and the
Molecular Basis of Heredity
• Topics
– Sexual reproduction (advantages,
disadvantages, meiosis)
– Mendelian inheritance
– Experimental genetics
Simple Inheritance
• Bacteria and some other organisms
reproduce simply by making exact copies
of themselves
• This is asexual reproduction
• The basic mechanism for most unicellular
eukaryotes is mitosis
Mitosis
• Mitosis is part of the
eukaryotic cell cycle, which
consists of two growth
phases (G1, G2), a
synthesis phase (S), and
an M phase during which
cell division occurs
Mitosis
• During M-phase, a cell
must complete a nuclear
division and a cytoplasmic
division and faithfully
distribute replicated
chromosomes to each
daughter nucleus
Mitosis
• Although they overlap extensively, Mphase is typically divided into six phases
Mitosis
• Although they overlap extensively, Mphase is typically divided into six phases
Mitosis
• Although they overlap extensively, Mphase is typically divided into six phases
Mitosis
• Although they overlap extensively, Mphase is typically divided into six phases
Mitosis
• Although they overlap extensively, Mphase is typically divided into six phases
Mitosis
• Although they overlap extensively, M-phase is
typically divided into six phases
• Animal cells and plant cells differ with respect to
cytokinesis
Mitosis
• Movie
Sexual Reproduction
• Sexual reproduction involves the mixing of genomes
from two individuals to produce offspring that are
genetically distinct from either parent and from other
offspring
• Disadvantages –
–
–
–
–
Half of your genes don’t make it to the next generation
very costly to produce specialized cells
interaction with other organisms is dangerous
mixing genes can produce unexpected results
• Advantages
– One word – variation
– The introduction of variation allows for better survival in a
changing environment and for the rapid spread or reduction of
advantageous and deleterious genes – (see video on guppies)
Sexual Reproduction
• Sexual reproduction occurs in diploid
organisms
– Diploid organisms have two complete sets of
chromosomes, one from each parent
– Diploid organisms therefore carry two copies
of most genes
– Diploid organisms use haploid cells to
reproduce
– Haploid cells contain only one copy of each
chromosome set
Sexual Reproduction
• The basics of sexual reproduction
– The germ cells (gametes) are haploid
– Gametes are generated through meiosis
– There are typically two types in animals
• A large, immobile egg
• Small, mobile sperm
– During sexual reproduction,
the gametes fuse to produce
a diploid zygote
Sexual Reproduction
• Primordial germ cells
are produced by
mitosis
• Ova and sperm by
meiosis
• Spermatogenesis
continues throughout
male mammals life
• Increased mutation
rate in males due to
increased number of
replication events
Sexual Reproduction:
Mitosis review
• Diploid cells reproduce
through mitosis
• This NOT how gametes
are made
Sexual Reproduction:
Meiosis (producing gametes)
• In mitosis, a diploid cell produces two diploid
daughter cells
• In meiosis, a diploid cell gives rise to four haploid
cells
Sexual Reproduction:
Meiosis (producing gametes)
• Major differences between mitosis and
meiosis
– Mitosis – once cell division
– Meiosis – two cell divisions
– Mitosis – replicated chromosomes line up
‘single file’ during metaphase
– Meiosis – replicated homologs line up in pairs
during metaphase I and ‘single file’ in
metaphase II
Sexual Reproduction:
Meiosis (producing gametes)
Sexual Reproduction:
Meiosis (producing gametes)
• Variation is introduced to the offspring by
combining the chromosomes of both parents into
a single cell
• A second level of variation is introduced via
recombination during meiosis (prophase I)
• Recombination is an exchange of material
between homologous chromosomes via a
process called ‘crossing over’
• Thus, the gametes you produce will be novel
combinations of the chromosomes you received
from your parents
Sexual Reproduction:
Recombination
Sexual Reproduction:
Recombination
Sexual Reproduction:
Recombination
• The end result of meiosis is a pool of gametes in
which the genetic information of the parent has
been extensively rearranged
• Merely by combining different sets of paternal
and maternal chromosomes, there are 223
(8,400,000) distinct gametes possible
• By introducing recombination you increase that
number exponentially
Sexual Reproduction:
Creating variation
Sexual Reproduction:
Mistakes during meiosis
– A cell must keep track of 92 chromosomes
(23 x 4) during meiosis and sometimes errors
occur
– Nondisjunction – failure of chromosomes to
separate properly
• Results in gametes with more or fewer than the
standard number
Sexual Reproduction:
Nondisjunction
– Zygotes resulting from aneuploid
(abnormal chromosome number)
gametes typically don’t survive
but sometimes do
– Down syndrome (trisomy 21)
– Edward’s syndrome (trisomy 18)
– Patau’s syndrome (trisomy 13)
Sexual Reproduction:
Fertilization
• Fertilization is the union of two
gametes to produce a diploid
zygote
• ~200 of the 3 million sperm in a
human male ejaculate reach the
egg
• To ensure only one sperm
fertilizes the egg, a chemical
cascade ‘hardens’ the egg once
one has fused with it
Sexual Reproduction:
Fertilization
• Ca++ Wave During Sea
Urchin Egg Fertilization
– The sperm enters at about
the 2 o'clock position. Note
the elevation of the
fertilization membrane in the
left panel and the calcium
wave in the right panel.
Mendelian Inheritance
• As a result of the processed described for
sexual reproduction, the genomes of
diploid organisms are a mixture of discrete
segments of their parents’ genomes
• Some traits are inherited in a simple
fashion through individual genes.
• Other traits are polygenic
• Others are simple and/or polygenic and
influenced by the environment
Mendelian Inheritance
• Simple Mendelian inheritance
– Attached earlobes
– PTC (phenylthiocarbamide) tasting
– ‘uncombable hair’
• Complex (polygenic) inheritance
– Eye color
– Height
• Studying inheritance in humans is difficult
for ethical reasons but more easily done in
other organisms
Mendelian Inheritance
• Named for Gregor Mendel
– 1822-1884
– Studied discrete (+/-, white/black) traits in pea
plants
Mendelian Inheritance
• Mendel began with true-breeding plants
– True-breeding - when mated with themselves
or others of the same type, produce the same
offspring
– Cross-pollinated these true breeding varieties
– Crossed the offspring (F1’s) with each other
or back to the parents
– Kept very detailed numerical records of the
offspring of each cross
Mendelian Inheritance
• A classic experiment
• What did it tell Mendel?
– That pod color was inherited as
a discrete trait, inheritance was
not ‘blended’ for this trait
– That one trait was ‘dominant’
over the other
• yellow + green ≠ yellow-green
• yellow + green = yellow
Mendelian Inheritance
• By continuing the experiment,
more can be learned
– The trait that was ‘lost’ in the first
generation (F1) was regained by the
second (F2)
• yellow + yellow = yellow and green
– The cause of the trait was not
destroyed, but was harbored unseen
in the parent
– There was a definite mathematical
pattern to the occurrence of the traits
(3:1)
Mendelian Inheritance
• Mendel concluded:
– Heredity was caused by discrete
‘factors’ (genes)
– These ‘factors’ remain separate
instead of blending
– The ‘factors’ came in different ‘flavors’
(alleles)
– Each offspring must inherit one gene
from each parent (2 total)
– The phenotype (appearance) of the
plants was determined by the
genotype (actual combination of
alleles)
Mendelian Inheritance
• Genotype vs. phenotype
Mendelian Inheritance
• The true-breeders only had one type of
allele (homozygous)
• Each parent passes on one of the alleles
they have to the offspring
• The first generation will all be heterozygous
(have two different alleles)
• One of the alleles is able to block the other
(yellow is dominant vs. green is recessive)
• The F1’s pass on both of their alleles in a
random manner
• Mendel’s Law of Segregation – the alleles
for a trait separate randomly during gamete
formation and reunite at fertilization
Mendelian Inheritance
• Mendel’s results held true
for other plants (corn,
beans)
• They can also be
generalized to any
sexually reproducing
organism including
humans
Mendelian Inheritance
• Humans don’t typically have families large enough to see
mendelian ratios
• Inheritance can be tracked through the use of pedigrees
• Are the traits in white and black dominant or recessive?
Mendelian Inheritance
BB
bb
Bb
Bb
Bb
Bb
Bb
Bb
bb
Bb
bb
bb
bb
Bb
• If the trait indicated in
black is dominant we
would expect the cross
Bb
between 2 and 3 to
produce either 100%
black trait offspring or
~50% black trait and
~50% white trait
offspring
Bb
• That ain’t the case
Mendelian Inheritance
bb
BB
Bb
Bb
Bb
Bb
Bb
Bb
• If the trait indicated in
black is recessive we
would expect the cross
between 2 and 3 to
produce all white trait
offspring
• Although it is possible
for individual 3 to have
a Bb genotype, it is
unlikely (0.56 = 0.016)
• What is the genotype of
#2’s sister?
Mendelian Inheritance
• Using the information from the previous slides we can
deduce most individual’s genotypes
Bb
BB
B?
bb
Bb
B?
B?
Bb
Bb
bb
Bb
Bb
Bb
Bb
Bb
Bb
Bb
bb
Bb
bb
bb
bb
bb
Bb
bb
bb
Mendelian Inheritance
• The examples above are referred to as
monohybrid crosses since they deal with
only one trait at a time
• Mendel also followed dihybrid crosses in
which two traits are followed at once
• Would the traits segregate as a single unit
or independently?
Mendelian Inheritance
• A dihybrid cross
Mendelian Inheritance
• A dihybrid cross produced all
possible phenotypes and
genotypes
• Thus, all of the alleles behaved
independently of one another
• Mendel’s Law of Independent
Assortment – Each pair of alleles
segregates independently during
gamete formation
Mendelian Inheritance
• Mendel’s Laws of Segregation and Independent
Assortment are a result of the process of meiosis
• During meiosis, the chromosomes that carry alleles are
distributed randomly among the resulting gametes
– The law of segregation
• Traits (genes) residing on one chromosome are
distributed independently of those on other
chromosomes
– The law of independent assortment
DNA Analysis: DNA Cloning
Mendelian Inheritance
• Mendel’s Laws of Segregation and Independent
Assortment are a result of the process of meiosis
• During meiosis, the chromosomes that carry alleles are
distributed randomly among the resulting gametes
– The law of segregation
• Traits (genes) residing on one chromosome are
distributed independently of those on other
chromosomes
– The law of independent assortment
• What about genes that reside on the same
chromosome? Do they also assort independently?
Mendelian Inheritance
• Yes, generally genes on the same
chromosome behave just like genes
on different chromosomes – they
assort independently
• How?
• Remember recombination and
crossing-over?
Mendelian Inheritance
Typically, several cross-over events will occur between
well-separated genes on the same chromosome. Therefore,
genes E and F or D and F are no more likely to be co-inherited
than genes on different chromosomes.
Genes that are very close together (A and B), on the other hand,
are less likely to have cross-over events occur between them.
Thus, they will often be co-inherited (linked) and do not
strictly follow the Law of Independent Assortment.
Non-Mendelian Inheritance:
Linkage Maps
• By following the rates of recombination between
genes on the same chromosome, we can
determine where they are in relation to each
other
• The results of these studies is called a linkage
map
• Linkage maps are based on the frequency with
which two genes are co-inherited. The closer
they are to each other, the more often they are
co-inherited.
DNA Analysis: Nucleic Acid
Hybridization
Mendelian Inheritance:
Genotypes and Phenotypes
• The genotype has an effect on the phenotype
but not vice-versa
• Heterozygotes tell us whether an allele is
dominant or recessive
– Heterozygotes harbor two alternative alleles of a gene
• Why does the allele for round peas (dominant)
mask the effect of the allele for wrinkled peas
(recessive)?
RR
rr
Rr
Rr
Rr
Rr
Rr
Mendelian Inheritance:
Genotypes and Phenotypes
• The gene in question encodes an enzyme that
converts sugars into starch
• ‘R’ is the active allele, ‘r’ is an allele that doesn’t
encode an active enzyme (a loss-of-function
mutant)
• RR genotype > both alleles produce active enzyme >
round pea phenotype
• rr genotype > neither allele produces active enzyme >
wrinkled pea phenotype
• Rr genotype > the active allele produces enough
enzyme to overcome the enzyme deficiency > round pea
phenotype
Mendelian Inheritance:
Genotypes and Phenotypes
• Gain-of-function mutants are usually
dominant
• These types of mutations may cause a
gene to produce hyperactive enzymes
– Ex. One allele of the Ras gene in human is a gain-offunction mutant that makes the enzyme active at
inappropriate times. Cells grow out of control >
cancer
Mendelian Inheritance:
Genotypes and Phenotypes
• In chapter 9 we discussed how variation in the
starting point for evolutionary change
• Most mutations are deleterious or neutral but
some can increase an organism’s fitness
• Others can be deleterious in
one environment but
advantageous in another
– Sickle cell disease
– Advantageous in malaria prone
areas, deleterious elsewhere
Experimental Genetics
• Once it became clear how traits were
inherited it became possible to manipulate
those traits in an effort to diagnose and
treat human disease
Experimental Genetics
• The classical approach
– Introduce mutations into an organism via
mutagenesis
– Mutagens are factors (radiation, chemicals)
that can cause damage to DNA and
chromosomes
– Once mutants are created, we then work
backward from the phenotype to determine
the genotype
Experimental Genetics
• The classical approach
– Not readily implemented in humans for
obvious reasons but still possible…
– Using model organisms. Many genes are
shared between us and flies, mice and worms
– Using cultured cells. The effected cells can
be removed, cultured and observed outside of
the human body
– Using non-lethal traits that have arisen
naturally (i.e. sickle cell)
Experimental Genetics
• Genetic Screens
– The more complex the genome, the harder it
is to locate the mutant phenotype of interest
– Genetic screens make the process easier by
selecting for mutants of interest
– Ex. Temperature sensitive mutants
Experimental Genetics
• Temperature sensitive mutants contain alleles
that are inactive (often lethal) at certain
temperatures
– Usually the genes involve critical processes such as
RNA synthesis or cell cycle control
– Isolating the mutant organisms is as simple as raising
the thermostat a degree or two
Experimental Genetics
• Complementation tests
– Complementation tests reveal whether two
mutations causing the same phenotype reside
in the same gene
– This allows us to count the number of genes
determining a particular phenotype
Experimental Genetics
• Complementation tests
Experimental Genetics
• Again, experiments like this on humans
are frowned upon
• How do we investigate mutant human
genotypes?
• One method involved haplotype blocks
Experimental Genetics
• Haplotype blocks are groups of sequences
along a chromosome that tend to be
inherited as a unit as a result of linkage
• By tracking single nucleotide
polymorphisms (SNPs) we can identify the
linked mutations that underlie a disease
20_30_trace_inheritance.jpg
Experimental Genetics
• Haplotype blocks can also be used to
identify recent mutations and mutations
that have been under positive selection
• The more recent the mutation, the larger
the haplotype block since it has not been
broken up through recombination
• Selectively advantageous mutations will
spread more quickly through populations
via large haplotype blocks
20_31_haplotype_blocks.jpg
Experimental Genetics
• What about traits that ‘run in families’ but are not
discrete?
• Traits that do not follow Mendel’s laws but do
have an inherited component are called complex
traits
• Reasons for complexity
– They are polygenic
– They have an environmental component
– They are polygenic and have an environmental
component
Experimental Genetics
• Polygenic traits may produce a continuum
of traits instead of simple discrete states
– Eye color – polygenic, numerous genes
contribute to the distribution of melanin in the
iris and each gene has several alleles
Experimental Genetics
• Environmental factors
– Even if you have all the genes necessary to be a fine
athlete, if you don’t exercise and practice you won’t
be
– Studies of identical twins adopted by different families
have helped increase our understanding of the
relative influence of genes and the environment