Lecture 15: Genes and Proteins

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Lecture 15 Genes and Proteins
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Outline

• Genes vs Proteins
• Genotypes vs Phenotypes
• One-gene-one-enzyme relation
• One functional protein with multi genes

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Genes vs Proteins
Genes --------gt heritable units dictating
phenotypes, in modern
terms, genes DNA sequences
two units (alleles) for diploid organisms
segregation and independent
assortment (meiosis)
Proteins -----gt functional units derived from
genes in modern terms,
proteins amino acid sequence DNA seq.
many different types of
proteins enzymes
transporter
structural proteins
different types of proteins
dictate their functional outcome
(phenotypes) in a different ways

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Genotypes vs Phenotypes
Genes ------------------gt Genotypes
homozygous

heterozygous Proteins ------------------gt
Phenotypes
1. dominant/recessive
2. codominance/incomplete dom.
What is the
molecular basis for dominance and recessiveness
by two alleles? two alleles -----gt two
slightly different forms of a gene
------gt two slightly different
DNA sequences

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One-gene-one-enzyme model
Protein (gene product) is enzyme.
enzyme Substrate --------------gt
product Two alleles (dominant A functional
recessive a defective) Phenotyp
e (AA or Aa normal aa
blockage of a pathway
substrate accumulate product
be in short supply)
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One-gene-one-enzyme model
Human disease Alkaptonuria caused by
mutation in Homogentisic Acid (HA)
oxidase. Human disease Phenylketonuria (PKU)
caused by mutation in phenylalanine
hydroxylase symptoms high levels of
Phe low IQ
low levels of Tyr Melanin
fair hair and complexion
pleiotropy
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One protein with multi genes

• Many proteins are made of more than one gene
  product, and require the right
• three dimensional structure of each protein
  component.
• In may cases, small changes in one gene as an
  allele can easily cause different structures,
• which subsequently result in functional outcome
  (phenotype) even if heterozygous.
• ---------gt codominance

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Sickle-cell anemia
Caused by single amino acid change in ?-globin
----gt sickle-shaped blood cells symptoms
anemia and others GAG (Glu) -------gt GTG
(Val) Hemoglobin has tetrameric structure 2
?? 2 ?-globin
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Sickle-cell anemia
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Sickle-cell anemia
Genotype vs phenotype Two different forms of
?-globin form tetrameric form in a random
association manner
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Exercise questions
The sickle cell anemia is usually caused by a
mutation at the 6th position of amino acid in the
?-globin protein. This single amino acid change
is responsible for making a modified structure of
hemoglobin. One hemoglobin is made of two copies
of each of ?- and ?-globins, and thus hemoglobin
has a tetrameric structure. In heterozygous
individuals (Hb?A/ Hb?S), how much percentage of
this tetrameric hemoglobin will contain the
modified version of ?-globin that eventually
causes anemia? Lets assume that the hemoglobin
is made of one copy of each of ?- and ?-globins,
meaning that hemoglobin has a dimeric structure.
In this case, how much percentage of this dimeric
hemoglobin will contain the modified version of
?-globin in heterozygous individuals (Hb?A/
Hb?S)?