The study of inherited traits: An introduction Genetics The study of inherited traits: An introduction

Molecular Genetics Cell Chromosome DNA Nucleus Nucleotides

History of Genetics Mid 19th century (1850) Darwin & Wallace Lamarck Theories of evolution Lamarck Theories on acquisition of heritable traits Mendel Theories on transmission of traits

History of Genetics Pioneering work of Mendel was done in ignorance of cell division – particularly meiosis, and the nature of genetic material – DNA 1869 - Friedrich Miescher identified DNA 1900-1913 Chromosomal theory of inheritance – Sutton & Boveri Genes on chromosomes – TH Morgan Genes linearly arranged on chromosomes & mapped – AH Sturtevant 1941 – George Beadle & Ed Tatum related "gene" to enzyme & biochemical processes 1944 – Oswald Avery demonstrated that DNA was genetic material

Early Ideas Until the 20th century, many biologists erroneously believed that characteristics acquired during lifetime could be passed on characteristics of both parents blended irreversibly in their offspring

Mendel Modern genetics began with Gregor Mendel’s quantitative experiments with pea plants Stamen Carpel Figure 9.2A, B

This illustration shows his technique for cross-fertilization Mendel crossed pea plants that differed in certain characteristics and traced the traits from generation to generation White 1 Removed stamens from purple flower Stamens Carpel 2 Transferred pollen from stamens of white flower to carpel of purple flower PARENTS (P) Purple 3 Pollinated carpel matured into pod This illustration shows his technique for cross-fertilization 4 Planted seeds from pod OFF-SPRING (F1) Figure 9.2C

Mendel studied seven pea characteristics - phenotypes FLOWER COLOR Purple White FLOWER POSITION Axial Terminal He hypothesized that there are alternative forms of genes (although he did not use that term), the units that determine heredity SEED COLOR Yellow Green SEED SHAPE Round Wrinkled POD SHAPE Inflated Constricted Phenotype expression of a specific trait, such as stature or blood type, based on genetic and environmental influences. Genotype refers to the genetic make-up of an organism POD COLOR Green Yellow STEM LENGTH Figure 9.2D Tall Dwarf

Principle of Segregation From his experimental data, Mendel deduced that an organism has two genes (alleles) for each inherited characteristic One characteristic (phenotype) comes from each parent P GENERATION (true-breeding parents) Purple flowers White flowers All plants have purple flowers F1 generation Fertilization among F1 plants (F1 x F1) Alleles Organisms have two alleles for each trait - form of a gene (one member of a pair) F2 generation 3/4 of plants have purple flowers 1/4 of plants have white flowers Figure 9.3A

GENETIC MAKEUP (ALLELES) A sperm or egg carries only one allele of each pair GENETIC MAKEUP (ALLELES) PLANTS PP pp Gametes All P All p The pairs of alleles separate when gametes form This process describes Mendel’s law of segregation Alleles can be dominant or recessive F1 PLANTS (hybrids) All Pp Gametes 1/2 P 1/2 p P P Eggs Sperm PP F2 PLANTS p p Pp Pp Phenotypic ratio 3 purple : 1 white pp Genotypic ratio 1 PP : 2 Pp : 1 pp Figure 9.3B

Homologous chromosomes bear the two alleles for each characteristic Alternative forms of a gene (alleles) reside at the same locus on homologous chromosomes GENE LOCI DOMINANT allele P a B P a b RECESSIVE allele GENOTYPE: PP aa Bb HOMOZYGOUS for the dominant allele HOMOZYGOUS for the recessive allele HETEROZYGOUS Figure 9.4

The principle of independent assortment By looking at two characteristics at once, Mendel found that the alleles of a pair segregate independently of other allele pairs during gamete formation This is known as the principle of independent assortment

HYPOTHESIS: DEPENDENT ASSORTMENT HYPOTHESIS: INDEPENDENT ASSORTMENT RRYY rryy P GENERATION RRYY rryy Gametes RY ry Gametes RY ry F1 GENERATION RrYy RrYy Eggs 1/2 RY 1/2 RY Sperm Eggs 1/4 RY 1/4 RY 1/2 ry 1/2 ry 1/4 rY 1/4 rY RRYY 1/4 Ry 1/4 Ry RrYY RrYY F2 GENERATION 1/4 ry 1/4 ry RRYy rrYY RrYy RrYy RrYy RrYy RrYy Yellow round 9/16 Actual results contradict hypothesis Green round rrYy RRyy rrYy 3/16 ACTUAL RESULTS SUPPORT HYPOTHESIS Rryy Rryy Yellow wrinkled 3/16 Yellow wrinkled rryy 1/16 Figure 9.5A

Independent assortment of two genes in the Labrador retriever Blind Blind PHENOTYPES Black coat, normal vision B_N_ Black coat, blind (PRA) B_nn Chocolate coat, normal vision bbN_ Chocolate coat, blind (PRA) bbnn GENOTYPES MATING OF HETEROZYOTES (black, normal vision) BbNn BbNn PHENOTYPIC RATIO OF OFFSPRING 9 black coat, normal vision 3 black coat, blind (PRA) 3 chocolate coat, normal vision 1 chocolate coat, blind (PRA) Figure 9.5B

Geneticists use testcross to determine unknown genotypes The offspring of a testcross often reveal the genotype of an individual when it is unknown TESTCROSS: GENOTYPES B_ bb Two possibilities for the black dog: BB or Bb B B b GAMETES b Bb b Bb bb OFFSPRINGa Figure 9.6 All black 1 black : 1 chocolate

Mendel’s principles reflect the rules of probability Inheritance follows the rules of probability The rule of multiplication and the rule of addition can be used to determine the probability of certain events occurring F1 GENOTYPES Bb female Bb male Formation of eggs Formation of sperm 1/2 B B 1/2 B B 1/2 b b 1/2 1/4 b B B b 1/4 1/4 b b F2 GENOTYPES 1/4 Figure 9.7

Family pedigrees The inheritance of many human traits follows Mendel’s principles and the rules of probability Figure 9.8A

Family pedigrees are used to determine patterns of inheritance and individual genotypes Dd Joshua Lambert Dd Abigail Linnell D_ John Eddy ? D_ Hepzibah Daggett ? D_ Abigail Lambert ? dd Jonathan Lambert Dd Elizabeth Eddy Pedigrees – charts that illustrate genetic ancestry Dd Dd dd Dd Dd Dd dd Female Male Deaf Figure 9.8B Hearing

Many inherited disorders are controlled by a single gene Most such disorders are caused by autosomal recessive alleles Examples: cystic fibrosis, sickle-cell disease Normal Dd Normal Dd PARENTS D D Eggs Sperm DD Normal d d Dd Normal (carrier) Dd Normal (carrier) OFFSPRING Autosomal: Pertaining to a chromosome that is not a sex chromosome; relating to any one of the chromosomes save the sex chromosomes. People normally have 22 pairs of autosomes (44 autosomes) in each cell together with two sex chromosomes (X and Y in the male and XX in the female). dd Deaf Figure 9.9A

A few are caused by dominant alleles Examples: achondroplasia, Huntington’s disease Figure 9.9B

Table 9.9

Fetal testing for inherited disorders Karyotyping and biochemical tests of fetal cells and molecules can help people make reproductive decisions Fetal cells can be obtained through amniocentesis Amniotic fluid withdrawn Centrifugation A karyotype is the characteristic chromosome complement of a eukaryote species Amniotic fluid Fluid Fetal cells Fetus (14-20 weeks) Biochemical tests Placenta Several weeks later Figure 9.10A Uterus Cervix Karyotyping Cell culture

Some biochemical tests Chorionic villus sampling is another procedure that obtains fetal cells for karyotyping Fetus (10-12 weeks) Several hours later Placenta Suction Karyotyping Fetal cells (from chorionic villi) Some biochemical tests Chorionic villi Figure 9.10B

Examination of the fetus with ultrasound is another helpful technique Figure 9.10C, D

Mendel’s principles are valid for all sexually reproducing species VARIATIONS ON MENDEL’S PRINCIPLES The relationship of genotype to phenotype is rarely simple Mendel’s principles are valid for all sexually reproducing species However, often the genotype does not dictate the phenotype in the simple way his principles describe

Incomplete dominance results in intermediate phenotypes When an offspring’s phenotype—such as flower color— is in between the phenotypes of its parents, it exhibits incomplete dominance P GENERATION Red RR White rr Gametes R r Pink Rr F1 GENERATION 1/2 R 1/2 r 1/2 R 1/2 R Eggs Sperm Red RR 1/2 r 1/2 r Pink Rr Pink rR F2 GENERATION White rr Figure 9.12A

Incomplete dominance in human hypercholesterolemia GENOTYPES: HH Homozygous for ability to make LDL receptors Hh Heterozygous hh Homozygous for inability to make LDL receptors PHENOTYPES: LDL LDL receptor Cell Normal Mild disease Severe disease Figure 9.12B

9.13 Many genes have more than two alleles in the population In a population, multiple alleles often exist for a characteristic The three alleles for ABO blood type in humans is an example

The alleles for A and B blood types are codominant, and both are expressed in the phenotype Blood Group (Phenotype) Antibodies Present in Blood Reaction When Blood from Groups Below Is Mixed with Antibodies from Groups at Left Genotypes O A B AB Anti-A Anti-B O ii IA IA or IA i A Anti-B IB IB or IB i B Anti-A AB IA IB Figure 9.13

9.14 A single gene may affect many phenotypic characteristics A single gene may affect phenotype in many ways This is called pleiotropy The allele for sickle-cell disease is an example Pleiotropy is the condition in which a gene influences the phenotype of more than one part of the body.

Individual homozygous for sickle-cell allele Sickle-cell (abnormal) hemoglobin Abnormal hemoglobin crystallizes, causing red blood cells to become sickle-shaped Sickle cells Clumping of cells and clogging of small blood vessels Breakdown of red blood cells Accumulation of sickled cells in spleen Physical weakness Heart failure Pain and fever Brain damage Damage to other organs Spleen damage Anemia Impaired mental function Pneumonia and other infections Kidney failure Rheumatism Paralysis Figure 9.14

Genetic testing to detect disease-causing alleles Genetic testing can be of value to those at risk of developing a genetic disorder or of passing it on to offspring Figure 9.15B Dr. David Satcher, former U.S. surgeon general, pioneered screening for sickle-cell disease Figure 9.15A

A single characteristic may be influenced by many genes This situation creates a continuum of phenotypes Example: skin color Polygenic inheritance

Fraction of population P GENERATION aabbcc (very light) AABBCC (very dark) F1 GENERATION AaBbCc AaBbCc Eggs Sperm Fraction of population Skin pigmentation F2 GENERATION Figure 9.16

Genes are located on chromosomes THE CHROMOSOMAL BASIS OF INHERITANCE Chromosome behavior accounts for Mendel’s principles Genes are located on chromosomes Their behavior during meiosis accounts for inheritance patterns

The chromosomal basis of Mendel’s principles Figure 9.17

Genes on the same chromosome tend to be inherited together Certain genes are linked They tend to be inherited together because they reside close together on the same chromosome

Figure 9.18

Crossing over produces new combinations of alleles This produces gametes with recombinant chromosomes The fruit fly Drosophila melanogaster was used in the first experiments to demonstrate the effects of crossing over

A B a b B A a b A b a B Tetrad Crossing over Gametes Figure 9.19A, B

Figure 9.19C

9.20 Geneticists use crossover data to map genes Crossing over is more likely to occur between genes that are farther apart Recombination frequencies can be used to map the relative positions of genes on chromosomes Chromosome g c l 17% 9% 9.5% Figure 9.20B

Alfred H. Sturtevant, seen here at a party with T. H Alfred H. Sturtevant, seen here at a party with T. H. Morgan and his students, used recombination data from Morgan’s fruit fly crosses to map genes Figure 9.20A

A partial genetic map of a fruit fly chromosome Mutant phenotypes Short aristae Black body (g) Cinnabar eyes (c) Vestigial wings (l) Brown eyes Long aristae (appendages on head) Gray body (G) Red eyes (C) Normal wings (L) Red eyes Wild-type phenotypes Figure 9.20C

A human male has one X chromosome and one Y chromosome SEX CHROMOSOMES AND SEX-LINKED GENES Chromosomes determine sex in many species A human male has one X chromosome and one Y chromosome A human female has two X chromosomes Whether a sperm cell has an X or Y chromosome determines the sex of the offspring

Parents’ diploid cells (male) (female) Parents’ diploid cells X Y Male Sperm Egg Offspring (diploid) Figure 9.21A

Other systems of sex determination exist in other animals and plants The X-O system The Z-W system Chromosome number Figure 9.21B-D

Sex-linked genes exhibit a unique pattern of inheritance All genes on the sex chromosomes are said to be sex-linked In many organisms, the X chromosome carries many genes unrelated to sex Fruit fly eye color is a sex-linked characteristic Figure 9.22A

Their inheritance pattern reflects the fact that males have one X chromosome and females have two These figures illustrate inheritance patterns for white eye color (r) in the fruit fly, an X-linked recessive trait Female Male Female Male Female Male XRXR XrY XRXr XRY XRXr XrY XR XR Xr Xr XR XR XRXr Y XRXR Y XRXr Y Xr Xr XRY XrXR XRY XrXr XRY XrY XrY R = red-eye allele r = white-eye allele Figure 9.22B-D

Sex-linked disorders affect mostly males Most sex-linked human disorders are due to recessive alleles Examples: hemophilia, red-green color blindness These are mostly seen in males A male receives a single X-linked allele from his mother, and will have the disorder, while a female has to receive the allele from both parents to be affected Figure 9.23A

Czar Nicholas II of Russia A high incidence of hemophilia has plagued the royal families of Europe Queen Victoria Albert Alice Louis Alexandra Czar Nicholas II of Russia Alexis Figure 9.23B

DNA 1953 - James Watson, Francis Crick, Rosalind Franklin & Maurice Wilkins Lead to understanding of mutation and relationship between DNA and proteins at a molecular level 1959 – “Central Dogma” DNARNAprotein

Genetic Concepts Chromosome – condensed chromosome Chromosome – double stranded DNA molecule packaged by histone & scaffold proteins 30nm fiber nucleosome DNA double helix

Genetic Concepts Chromosome numbers Karyotype Constant for an organism n - haploid number 2n – diploid number Karyotype

Genetic Concepts Y

Genetic Concepts Chromosome numbers Each individual inherits n # of chromosomes from dad & n # from mom Humans - 46 chromosomes = 2n Humans 23 paternal, 23 maternal Humans n = ____ Each maternal & paternal pair represent homologous chromosomes - called homologs

Genetic Concepts Diploid Haploid (a) Chromosomal composition found 1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 9 10 11 12 13 14 15 16 17 18 19 20 21 22 XX 17 18 19 20 21 22 X (a) Chromosomal composition found in most female human cells (46 chromosomes) (b) Chromosomal composition found in a human gamete (23 chromosomes) Diploid Haploid

Genetic Concepts Homologous Chromosomes Share centromere position Share overall size Contain identical gene sets at matching positions (loci) gene for color gene for shape

Genetic Concepts Gene – sequence of DNA which is transcribed into RNA rRNA, tRNA or mRNA Locus – the position on a chromosome of a particular DNA sequence (gene) G Locus – gene for color W Locus – gene for shape

Genetic Concepts DNA is mutable A variation in DNA sequence at a locus is called an allele Diploid organisms contain 2 alleles of each locus (gene) Alleles can be identical – homozygous Alleles can be different – heterozygous If only one allele is present – hemizygous Case in males for genes on X and Y chromosomes

Genetic Concepts Allele – G vs g; W vs w At the G locus either the G or g allele may be present on a given homologue of a homologous pair of chromosomes

Genetic Concepts Genome Genotype Phenotype Collection of all genetic material of organism Genotype Set of alleles present in the genome of an organism Phenotype Result of Gene Expression Genes (DNA) are transcribed into RNA mRNA is translated into protein, tRNA & rRNA work in translation process Biochemical properties of proteins, tRNAs & rRNAs determine physical characteristics of organism

Gene Expression DNA Gene Transcription RNA (messenger RNA) Translation Protein (sequence of amino acids) Functioning of proteins within living cells influences an organism’s traits.

Mutation & Phenotypic Variation Pigmentation gene, dark allele light allele Transcription and translation Highly functional pigmentation enzyme Poorly functional Molecular level

Mutation & Phenotypic Variation Wing cells Lots of pigment made Little pigment made Pigment molecule (b) Cellular level Pigmentation gene, dark allele light allele Transcription and translation Highly functional pigmentation enzyme Poorly functional (a) Molecular level

Mutation & Phenotypic Variation Dark butterfly Light butterfly Organismal level Dark butterflies are usually in forested regions. Light butterflies are usually in unforested regions. Populational level