Necessities of Life. Concepts of Genetics. DNA Structure. Reproduction: DNA. DNA Structure DNA. Molecules and Families

Transcription

1 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 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 The sides of the DNA ladder are composed of bonded sugar and phosphate, the rungs are based on hydrogen bonds 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. DNA Structure 1

2 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 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 DNA Transcription Protein Synthesis 2

3 Gene Regulation Humans and chimps share some 98% of their genes, but the regulation of those genes is what makes for the massive physical differences How does this work in Humans? 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 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 Genes Chromosome 16 Chromosome 11 Hemoglobin Loci Hemoglobin Phases 3

4 Mutation 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 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 4

5 Other Applications Stacy McGrath s thesis showing West 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 Nucleotide Sequencing Southern Blot Technique for DNA fingerprints Cycle Sequencing Illustration 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 Near the tip of the short arm of Chromosome 11 Mutation causes increased synthesis of insulin and IGF2 Microsatellite Insulin IGF2 Stress Response Result Work Cold Diet T h r i f t y G e n e s I G F 2 I N S Muscle Growth Skeletal Growth Insulin Insulin Resistance Strong limbs for paddling Low surface area to mass Fat deposition: Insulate body, store calories 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 5

6 Karyotype Human 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 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 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 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. 6

7 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: Hb S / Hb S Phenotype: Sickle Cell Anemia 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: Hb S / Hb A Phenotype: Sickle Cell Trait (Carrier) 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 Augustinian Monk Determined that the nature of inheritance was particulate (genes) Published findings in 1865 Was unknown until 1900 Gregor Mendel 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 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) 7

8 Mendelian Genetics 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 MEIOSIS The process of Meiosis accounts for the Law of Segregation GAMETES Punnett Square A O A AA AO O AO OO Independent Assortment 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 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 GAMETES A+ A- O+ O- A+ AA++ AA+- AO++ AO+- A- AA+- AA-- AO+- AO-- O+ AO++ AO+- OO++ OO+- O- AO+- AO-- OO+- OO-- 8

9 Autosomal Dominant: Huntington s Disease Autosomal Recessive: Phenylketonuria Sex-Linked Recessive: Hemophilia A 9