Lecture 1 - Introduction to Genetics - 2025 Slides PDF

Genetics Biology 202 Spring 2025 Dr. Nancy Fujishige Office hours: Featherston Life Sciences Building 287 Mondays and Wednesdays 2:00-3:00 pm, Or by appointment On Zoom: By appointment only...

Genetics Biology 202 Spring 2025 Dr. Nancy Fujishige Office hours: Featherston Life Sciences Building 287 Mondays and Wednesdays 2:00-3:00 pm, Or by appointment On Zoom: By appointment only https://lmula.zoom.us/j/796201568 [email protected] Slides and handouts are available online 1  Please introduce yourself ! (submit this info on Brightspace) 1. Name (your preferred name) 2. Are there specific aspects of Genetics that you would like to study in this course? Do you have any experience in this field? 3. What are your career plans? 4. Tell me something exciting about yourself. 5. Picture (optional) 2 Teaching Assistant Office hours TAs: Hannah Kotek Ashley Lee Monday – Thursday evenings 6:00 – 8:00 PM 3  class strategy problem solving! -- break down problems into small parts textbook readings textbook problems/exercises form study groups stay on top of the material! -- the topics build upon each other Attend office hours, if you need help! 4  Genetics in Genetics in the thenews news First CRISPR Sickle Cell Patient ‘Reborn’: FDA Approves Treatment Ellen Matloff, Forbes, December 8, 2023 Canada approves Pfizer's gene therapy for bleeding disorder (hemophilia) Christy Santosh, Reuters, Jan 3, 2024 Why scientists dug up the father of genetics, Gregor Mendel, and analyzed his DNA Nell Greenfieldboyce, NPR December 30, 2022 23andMe told victims of data breach that suing is futile, letter shows Ashley Belanger, Ars Technica, January 4, 2024 How DNA and an obituary helped ID a victim of the Green River killer DAVID GUTMAN, THE SEATTLE TIMES, JANUARY 2, 2024 Defying Genetics: How One Patient’s Unique Mutation Offers New Hopes in Alzheimer’s Prevention SciTech Daily December 25, 2023 Gene Mutation Protects Against Parkinson's Disease Ernie Mundell, US News and World Report, January 5, 2024 5  today’s lecture: quick review of molecular biology what is genetics? a brief history of genetics Mendelian analysis – Mendel’s experiments – Mendel’s Laws 6  review -- familiar concepts DNA structure and function central dogma of molecular biology DNA → RNA→ protein 7  remember DNA basics DNA is the genetic material of life 5’ 3’ 2 linear polymers of deoxyribonucleotide Each deoxyribonucleotide consists of – deoxyribose (5 C sugar) with a phosphate group & a nitrogenous base (A,C,T,G) The 2 polymers are – antiparallel 5’ → 3’ 3’  5’ – held together by Hydrogen bonds between base pairs – 4 nucleotide bases 5’ 3’ Adenine (A) pairs with Thymine (T) Guanine (G) pairs with Cytosine (C) 8 The Organization of DNA in a Cell Genome: all the genetic material in a set of chromosomes. haploid (1n) – 1 set diploid (2n) – 2 sets Chromosome: self-replicating genetic structures of cells that contain the DNA sequence of genes Gene: a sequence of nucleotides located in a particular position on a chromosome that encodes a specific functional product (RNA, protein) 9 central dogma – in action! 10  What is genetics? the branch of biology that deals with heredity and variation explores the relationship between genes and traits explains life at the level of molecules, organisms, and populations helps explain many biological phenomena – why children resemble parents – why certain diseases run in families – extinction of species with low populations 11  Genetics seeks to explain: What determines the different characteristics that are passed on from one generation to the next, and How are they passed on? What are the rules by which these characteristics are passed on? 12  next: a brief history of genetics – homunculus – blending hypothesis – Darwin’s gemmules Mendel and his experiments ─ his background ─ peas! ─ reciprocal crosses ─ Mendel’s theory ─ Mendel’s First Law ─ Mendel’s Second Law 13  History of genetics For many millennia people have recognized: – familial resemblance – diseases run in families – selection of animals, plants with useful traits ATTEMPTS TO EXPLAIN PATTERNS OF HEREDITY: Modern corn was homunculus bred from blending hypothesis a wild -- until late 1800’s Mexican Darwin’s gemmules grass called teosinte corn teosinte. 14  homunculus Aristotle (400 BC) believed that the offspring was preformed in the sperm. Microscopists believed they could see a fully formed miniature fetus (homunculus) in the head of each human sperm. led to belief that more inheritance came from the male parent learned in the mid-1800s: egg + sperm = zygote An imaginative drawing, after Nicholas Hartsoeker (1694) 15 blending hypothesis children as intermediates of parents – substances blended together to yield unique individual with traits from both parents X problem with blending hypothesis: – expects no extreme characteristics – not all children are “intermediate” between parents… the results of crosses were not always predictable 16  gemmules Darwin hypothesized particles (“gemmules”) were collected from all organs and became concentrated in sperm and egg (gametes) the use or lack of use of organs would affect inheritance he hoped it would help explain evolution Darwin later denied the validity of his own hypothesis 17  Kolreuter realized that these explanations were not sufficient in 1840 Kolreuter established that parental characteristics could X disappear for a cross generation and then reappear self this phenomenon could only be explained if units of heredity were particulate in nature … but this is as far as Kolreuter took it 18 Gregor Mendel the Father of Genetics an Austrian monk 1822 - 1884 19  Mendel’s background studied physics in Vienna (with Christian Doppler) also studied math and botany there was an agricultural interest in hybridization at the time his monastery was interested in learning the rules of hybridization Mendel was set to figure out how genetic information is transmitted from one generation to the next. 20 He brought SCIENTIFIC Methods to the study of heredity in the 1860s, Mendel brought to biology methods that were standard in physics – limited the number of variables – quantified results (counted and classified progeny) – came up with models that could be tested he organized, verified and repeated experiments other important aspects of Mendel’s work: – he selected a simple model system (used by others before him) 21 – he looked at more than one generation  Mendel studied the garden pea By the 1800’s methods for breeding peas were well- established It was known that heritable traits were 22 transmitted to offspring through pollen Peas can be self-fertilized or cross fertilized Self-fertilization: Pollen is allowed to fertilize its own ovules. Cross fertilization: Transfer pollen from one plant to the stigma of a second plant 23  Mendel was skeptical of the ideas of blending and gemmules but he was intrigued by the observations of Kolreuter… that traits can be lost in the hybrid, and then reappear in the next generation. parentals (P) X cross fertilize 1st filial generation hybrid (product of (F1) non-identical self fertilize parents) F2 self fertilize self fertilize green trait was lost, true breeding F3 but reappeared 24  Mendel was aware of the following characteristics of hybrids: P X cross their uniformity of phenotype* in the F1 F1 hybrid self their tendency to revert to parental phenotypes in F2 F2 *phenotype: visible characteristics (phene -- Greek, “appearance”) 25  Mendel did the following: 1. chose an excellent model system: Pisum sativum (garden pea) - many easily observable traits - can either “cross” or “self” pollinate - easily grown - fast generation time 2. used “pure,”or “true-breeding” - allowed to “self” for at least 2 generations - all progeny identical to parental strain 26 3. studied seven characteristics (true-breeding lines of each) - each characteristic had two possible phenotypes - each was governed (we know now) by one gene 27 4. performed reciprocal crosses to determine – if character was linked to sex – if one parent contributed more to progeny than the other X X purple white white purple (pollen) (ovule) (pollen) (ovule) 28  reciprocal crosses purple white purple white In F1: All purple offspring!! In this example, hybrids were always purple, regardless of parental contribution both parents contribute equally the flower color trait is not sex-linked 29 Mendel called purple dominant, white recessive  5. followed (and counted) all progeny to the F3 generation experimental design: F1 F2 pure breeding plant 1 X hybrid progeny self count progeny pure breeding plant 2 30 Mendel’s Breeding experiment 705 Purple- flowered Purple offspring flower Self-pollinate self cross until always get same 224 color white- In this First filial flowered (F1) generation offspring White trait is hidden – F2 generation RECESSIVE Phenotypic ratio: white PARENTS: Purple trait is visible – 3 purple: 1 white flower True- DOMINANT breeding Is the F1 individual true 31 breeding? Mendel’s Breeding experiment (cont.) 705 Purple- self All purple flowered offspring self OR 3 purple : 1 white 224 F1 generation self ALL white white- flowered flowered offspring offspring F2 generation F3 generation Phenotypic ratio: 3 purple: 1 white 32 All of the traits that Mendel studied showed the same inheritance pattern: One trait (defined as dominant) appeared in 3/4 of the offspring. The other “recessive” trait appeared in 1/4 of the progeny. 33 Since BOTH traits could be seen in the F2 generation, genetic determinants for BOTH traits must have passed from Parentals to the F1. For any given characteristic, each plant must have TWO genetic determinants controlling the phenotype. 34 How could 3:1 ratios be explained?? A single determinant A from the a egg and sperm come together in the ZYGOTE egg sperm Aa ZYGOTE 35  Mendel proposed: hereditary determinants behave like particles each adult pea has two determinants (which we now call alleles) for a character gametes have only one determinant for each character (of the two from each parent) each determinant segregates equally into gametes; which determinant a gamete gets is random union of two gametes occurs randomly with regard to genetic determinants 36  Mendel’s First Law Law of Equal Segregation – the two alleles of each trait separate (segregate) during gamete formation, then unite at random, one from each parent, at fertilization. 37 Molecular basis for the different appearance: Traits are encoded by genes The heritable factors are genes. Genes are segments of DNA that encode a gene product (a protein, tRNA, rRNA, etc.) Allele = one of at least two alternative forms of a gene. Example: flower color – This plant has an This plant has allele that can alleles that make pigment (P) cannot make pigment (p) P P p p This ADULT diploid individual makes…….these haploid gametes 38  Schematically: allele: different forms of the same gene P - dominant allele, purple p - recessive allele, white Each adult has two determinants: if both are the same: homozygous (e.g. – PP or pp) if they are different: heterozygous (e.g. – Pp) 39 A link between genotype and phenotype Mendel showed that there is a link between genotype (genetic constitution of allelic pair): Pp or PP pp and phenotype (physical appearance of organism): purple white The phenotype is specified by the concerted action of two alleles of one gene. 40 Let’s go through the cross using this nomenclature gamete has allele P PP Purple Self-pollinate cross Pp flower until always get same color Gamete has allele The First filial (F1) p individual is a HETEROZYGOTE. pp white flower True-breeding parents are HOMOZYGOTES 41 What happens when a heterozygote is self-pollinated? Pp The F1 heterozygote makes these gametes: eggs: ½ P or ½ p Sperm: ½ P or ½ p Self-pollinate Alleles in sperm A PUNNETT SQUARE is ½P ½ p used to figure out genotypes and phenotypes of the F2 progeny. ½P Phenotypic ratio ¼ PP alleles in eggs ¼ Pp 3: purple (PP or Pp) 1: white (pp) Genotypic ratio ½p 1: homozygous dominant (PP) 2: heterozygote (Pp) ¼ Pp ¼ pp 1: homozygous recessive (pp) 42  Conclusions from a monohybrid cross (heterozygous for a single–trait): Pp x Pp Phenotypes: Genotypes: Purple: White PP: Pp: pp 3 : 1 1: 2 : 1 what is another way to test this model of inheritance...? 43