Download Concepts of Genetics Necessities of Life Reproduction: DNA DNA

Necessities of Life
Concepts of Genetics
Molecules and Families
•Reproduction so that life can continue
generation after generation
–Facilitated by molecules from the chemical
family of Nucleic Acids
•Maintenance of essential physiological
functions of life (metabolism)
–Facilitated by molecules from the chemical
family known as Proteins
Reproduction: DNA
•Reproduction is based on the accurate
duplication of DNA
•The precise and accurate duplication of a
DNA molecule, known as Replication, is
made possible by the chemical structure of
the DNA molecule
DNA
DNA Structure
•Ladder or lattice-like molecule composed of
smaller building blocks: Nucleotides
•Nucleotides are composed of three subunits:
–Sugar (deoxyribose for DNA)
–Phosphate
–Nitrogenous base--the key to the functioning of
DNA
•Purines (2 N/C rings): Adenine, Guanine
•Pyrimidines (1 N/C ring): Thymine, Cytosine
DNA
Structure
•Thes
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between complementary nitrogenous bases
•The key to DNA function is the
complementarity of the bases: Adenine
bonds only with Thymine and Guanine only
with Cytosine.
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Replication
Maintenance
•Life functions are regulated by proteins:
–Structural proteins like the muscle cell building
block, myosin
–Regulating proteins, including enzymes and
hormones, like the enzyme that breaks down
starch molecules, salivary amylase
–Transporter proteins like the oxygen
transporter, hemoglobin
Protein Structure and Function
•Function of different proteins is based on
structure
•Structure is determined by the number and
type of building blocks, called Amino Acids
•Amino acids are assembled into chains called
polypeptides
•A functional protein may include several
polypeptides
DNA
Transcription
Protein Synthesis
•The sequence of amino acids in a
polypeptide is determined by the sequence
of nitrogenous bases in the DNA unit (or
gene) coding for that polypeptide.
•Protein synthesis is a two-step process:
–Transcription: copying the DNA to RNA
–Translation: using the RNA to assemble the
polypeptide
Protein Synthesis
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Gene
Regulation
How does this work in Humans?
Humans and chimps
share some 98% of
their genes, but the
regulation of those
genes is what makes
for the massive
physical differences
•The Hemoglobin molecule is a complex
protein structure that carries oxygen and
carbon dioxide through the blood stream
–It consists of four polypeptides: 2 alpha and 2
beta chains
–Each of these polypeptides has a separate
section of DNA carrying the code for the
appropriate sequence of amino acids
Hemoglobin Genes
Hemoglobin
•Each alpha chain consists of 141 Amino
Acids, requiring a sequence of 423
nucleotides in the DNA
•Each beta chain consists of 146 Amino
Acids, requiring a sequence of 438
nucleotides in the DNA
Hemoglobin Loci
Chromosome 16
Chromosome 11
Hemoglobin Phases
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Mutation
Sickle Cell Anemia
•Even small changes to the sequence of
nucleotides in the DNA can have significant
repercussions in terms of protein structure
and function
•Changes can involve single nucleotides or
large groups of nucleotides
•The result of mutation is determined by
what it does to the protein structure
•Sickle cell anemia is a genetic condition
caused by a point mutation: the change in
one nucleotide within the sequence of 438
bases coding for the hemoglobin beta chain
•The shift in the 17th nucleotide from a
Thymine base to an Adenine base causes a
shift in the 6th amino acid from glutamic
acid to valine
Sickle Cell Anemia
Point
Mutation
•The change of one amino acid results in
hemoglobin that has a tendency to clump
together and destroy the Red Blood Cells
that hold the molecules
•This produces a life-threatening disease that
has only come under some control by
modern medicine in the last few decades
Polymerase Chain Reaction
Applications in Anthropology
•Understand patterns of human variability
–Similarity and Differences between populations
are measured by sharing of DNA, proteins
•Reconstruct evolutionary relationships
–Discover chimp is closer than gorilla to man
•Estimate times of divergence of populations
–Mitochondrial Eve scenario suggests modern
man comes from Africa, ~200,000 years ago
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Other Applications
Nucleotide Sequencing
•St
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ho
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African affinity for DNA extracted from
skeletal remains excavated from an
unmarked cemetery
•Had to clean bones, grind up a sample, then
separate human from microbial mtDNA
Near the tip of the short arm of
Chromosome 11
Other Applications
•Knowledge of how the molecular structure
of the genes works facilitates models of
selection
•Summer of 2002 I wrote a text box on the
Thrifty genes in the peopling of Polynesia
–Argument bolstered by recent DNA sequencing
work in the vicinity of the Insulin gene
Stress
Response
Cold
T
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Diet
G
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Work
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S
•Southern Blot Technique for DNA
fingerprints
•Cycle Sequencing Illustration
Mutation causes
increased
synthesis of
insulin and
IGF2
Microsatellite
Insulin
IGF2
Result
Muscle
Growth
Strong limbs for
paddling
Skeletal
Growth
Low surface
area to mass
Insulin
Fat deposition:
Insulate body,
store calories
Insulin
Resistance
Spare glucose,
prevent ketosis
Chromosomes
•Chromosomes are the complex DNA and
Protein units that carry the genetic code in
all cells with nuclei
•In sexually-reproducing organisms,
chromosomes come in homologous pairs
–Each member of the pair contains information
on how to build the same protein products
–One member of each pair comes from the
mother and one comes from the father
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Human Karyotype
Karyotype
•A Karyotype is a photomicrograph of the
chromosomal complement of an individual
•The chromosomes are arranged according to
size, and numbered, with the first pair being
the largest chromosomes and the twentysecond pair being the smallest in humans,
except for the Y (male-determining)
chromosome
Human Genome
•Humans have 23 pairs of chromosomes
–22 pairs of autosomal chromosomes affecting
almost all aspects of the individual other than
sex
–1 set of sex determining chromosomes
•A pair of X chromosomes for Females
•One X and one Y chromosome for Males
•Approximately 100,000 genetic loci on the
23 pairs of chromosomes
Alleles
•Many genes have different forms
•We discussed two forms of the gene for
Hemoglobin, the normal form called type
A, and the mutant variety that results in
sickle cell, type S
•These variants of a particular gene are
called Alleles
Locus
•The position of a gene on an homologous
chromosome pair is known as a Locus
–The locus of the beta gene for the Hemoglobin
molecule is near the tip of the short arm of
chromosome number 11
–The locus of the alpha gene is near the tip of the
short arm of chromosome number 16
Genotype vs. Phenotype
•Genotype is the genetic makeup of an
individual
–This usually refers to what alleles an individual
has at a specific locus
•e.g., at the ABO locus, one A allele, one O allele
•Phenotype is the observable expression of
the genotype
–The phenotype for the above genotype would
be Blood Type A.
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Homozygous
•If an individual has two of the same alleles
at a particular locus, he is said to be
homozygous (or is a homozygote)
–A person is homozygous if he inherits a
Hemoglobin S allele from both his mother and
father
–Genotype: HbS/ HbS
–Phenotype: Sickle Cell Anemia
Dominant and Recessive
•Alleles are said to be dominant or recessive
depending upon whether they are expressed
(dominant) or hidden (recessive) in
heterozygotes
–In the ABO system, A and B alleles are
dominant over O, and co-dominant with each
other (Blood type AB)
–O is recessive to both A and B
Mendelian Genetics
•An individual can have two different types
of genes for a particular characteristic and
only express one type
–Example: ABO blood type system, if you have
both an A type gene and an O type gene, your
blood type is A, and your blood functions as
blood type A
Heterozygous
•If an individual has two different alleles at a
particular locus, he is said to be
heterozygous (or is a heterozygote)
–A person is heterozygous if he inherits a
Hemoglobin S allele from his mother and a
Hemoglobin A allele from his father
–Genotype: HbS/ HbA
–Phenotype: Sickle Cell Trait (Carrier)
Gregor Mendel
•Augustinian Monk
•Determined that the
nature of inheritance
was particulate (genes)
•Published findings in
1865
•Was unknown until
1900
Mendelian Genetics
•Law of Segregation
–Genes occur in pairs (because chromosomes
occur in pairs, one from the mother and one
from the father)
–During meiosis, chromosome pairs separate so
that each gamete contains one member of each
pair
–Each gamete has an equal (50-50) chance of
containing a particular maternal or paternal
chromosome (randomness)
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MEIOSIS
Mendelian Genetics
The process of
Meiosis accounts
for the Law of
Segregation
•Law of Independent Assortment
–Alleles that govern one trait sort into gametes
independently of the alleles for other traits-providing they are on separate chromosomes
–Chance governs which pairs of alleles from loci
on separate chromosomes are found in any
given gamete
Punnett Square
Independent Assortment
GAMETES
Father
A
Father
O
Mother
A
AA
AO
Mother
O
AO
OO
Genetic Linkage
•If two different genes have loci on the same
homologous chromosome pair, they are said
to be Linked
–The locus for insulin and the locus for tissue
compatibility (affects transplant rejections) are
both found on the sixth chromosome pair in
man
–These two genes are linked
•The ABO locus is on chromosome 9, the
Rhesus (Rh) locus in on chromosome 1
•These two factors are transmitted
independent of one another
–Phenotype (Blood type): A+
–Genotype: A/O +/–Gametes: A/+ A/- O/+ O/- in equal numbers
GAMETES
Father
A+
Father
A-
Father
O+
Father
O-
Mother
A+
AA++
AA+-
AO++
AO+-
Mother
A-
AA+-
AA--
AO+-
AO--
Mother
O+
AO++
AO+-
OO++
OO+-
Mother
O-
AO+-
AO--
OO+-
OO--
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Autosomal Dominant:
Hunt
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e
Autosomal Recessive:
Phenylketonuria
Sex-Linked Recessive:
Hemophilia A
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