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 i de so ft heDNA“ l a dde r ”a r e composed of bonded sugar and phosphate, t he“ r u ng s ”a r eba s e do nhy dr oge nbo nds 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 a c yMc Gr a t h’ st he s i ss ho wi ngWe s t 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 h r i f t y

Diet

G e n e s

Work

I G F 2

I N 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 i ngt on’ sDi s e a s e

Autosomal Recessive: Phenylketonuria

Sex-Linked Recessive: Hemophilia A

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