Genes To Traits PDF

GENES TO TRAITS **Gene** a basic unit of inheritance -- the instruction for a trait which is passed on from generation-to-generation are found in the DNA, but DNA genomes can be very large - the human genome contains \~3 billion bases - there are \~21000 genes in the human genome **Trait**...

GENES TO TRAITS **Gene** a basic unit of inheritance -- the instruction for a trait which is passed on from generation-to-generation are found in the DNA, but DNA genomes can be very large - the human genome contains \~3 billion bases - there are \~21000 genes in the human genome **Trait**: a heritable physical characteristic, can ba a heritable physiological characteristic The idea that proteins are the gene products proposed early 20th century The mold Neurospora crassa can grow on the minimal medium is the wild-type that has all genes functioning which are precusor, ornithine, citrulline and arginine, respectively. Is an autotroph -- it synthesizes all the molecules needed, including aa. -\> Conclude from experiment: one gene -- one protein **The molecular nature of the gene** Proteins are responsible for the physical nature of the traits Genes instruct protein synthesis DNA is the molecular nature of a gene Nucleotides is the molecular structure of a gene The Central Dogma of Molecular Biology: DNA -\> mRNA -\> protein Genes are found in the DNA, but DNA genomes can be very large \+ The human genome contains \~3 billion bases \+ there are \~21000 genes in the human genome \+ the average protein length is \~370aa. Every cell in an organism contains the same DNA, so proper instruction should contain information on not only what to make (protein) but also when, where, and how much of the protein to make. Therefore, a gene has two parts: a coding region, and a control region (promoter). **Molecular anatomy of a gene** **Molecular location of a gene** **+** A gene, the heritable instruction for a trait, is a segment of the DNA \+ Genomic DNA is a very large molecule \+ Contain thousand of genes arranged in a linear fashion along the DNA **DNA needs to be compacted** \+ With thousands of genes and other parts present in the DNA molecule, DNA length is enormous: \~1m of DNA in each of our nuclei. But the nucleus is much smaller than that (there are plants and animals with even larger genomes) \+ DNA needs compacting -- this is achieved by wrapping DNA around special proteins called histones. We call the resulting DNA-protein complex chromatin. \+ Chromatin is further compacted into increasing levels of compaction, resulting in special nuclear structures called: chromosomes **Chromosome** At the simples level, chromatin is a double-stranded helical structure of DNA. DNA is commplexed with histones to form nucleosomes. Each nucleosome consists of 8 histone proteins around which the DNA wraps to form loops averraging in length (fiber). The fibers are compressed and foled produces the chromatid of chromasome **Chromatin consists of DNA and proteins** \+ These proteins are called histones. \+ There are 5 types of histones: H1, H2A, H2B, H3 and H4. They are basic (alkaline, positively charged) relatively small proteins, that associate with the negatively charged phosphate-sugar backbone of DNA. \+ Two each of histone H2A, H2B, H3 and H4 proteins form a large octamer which is at the core of a nucleosome, a structure consisting of the histone octamer and 1.65 wraps of DNA molecule around it: \+ Ends of each histone molecule can protrude onto the surface of the chromatin/DNA and be chemically modified, which plays an important role in transcriptional activity of the DNA associated with such nucleosome **Consequences of chromosome organization** \+ Recall the Central Dogma: DNA needs to be accessible for transcription (i.e. various proteins need to be able to physically interact with the gene's promoter, RNA Polymerase II needs to be able to transcribe gene coding region). \+ **Problem**: Compacted chromatin makes DNA inaccessible \+ **Solution**: make parts of chromosome accessible by relaxing the compaction level. + 2 main types of chromatin: euchromatin (relaxed, transcribed) and heterochromatin (compact, transcriptionally silent) \+ Genes more likely to be found in euchromatin compartments on the chromosome **Chromosomes - karyotype** \+ The number of chromosomes is species-specific. Humans have 23 pairs of chromosomes. There are some plant (fern) species with \>1000 chromosomes in the nucleus, or ants with only 1 chromosome. \+ The entire human genome (DNA) therefore is packaged into 23 separate parcels of unequal size (and therefore, unequal genetic content). **Karyotype and karyogram** \+ Human karyotype contains 23 chromosome pairs \+ The disperse nature of the pseudo-colored interphase chromosomes in the nucleus vs. supercompact metaphase chromosomes in the karyotype (corner: sorted and paired up chromosomes =karyogram) **Summary** +Chromosomes are composed mainly of DNA and special proteins called histones. An unreplicated chromosome contains one continuous DNA molecule wrapped around histones. \+ After replication, a chromosome is composed of two identical double stranded DNA molecules compacted into 2 chromatids that are connected by a centromere (also called a primary constriction). Two chromatids make up one chromosome after DNA replication. \+ Genes are located on chromosomes. Each gene has its own address on a chromosome called a locus. \+ The information content of a gene is determined by the DNA sequence at a locus 26/8 GENE REGULATION IN PROKARYOTES AND EUKARYOTES **Masters of adaptation** \+ Bacteria thrive almost everywhere, including places too acidic, salty, cold, or hot for most other organisms \+ They have an astonishing genetic diversity \+ Most bacteria are microscopic, but what they lack in size they make up for in numbers \+ There are more in a handful of fertile soil than the number of people who have ever lived **Bacterial** \+ diversity vastly surpasses that of Archaea and Eukaryotes \+ are unicellular, and some species form colonies \+ Most bacterial cells are 0.5--5 µm, much smaller than the 10--100 µm of many eukaryotic cells \+ Bacterial cells have a variety of shapes \+ The three most common shapes are spheres (cocci), rods (bacilli), and spirals \+ in the environment: - Parasites: plants, animals (incl. humans) - Mutualists: (eg in our guts), nitrogen fixing rhizobia in legumes - Saprophytes: essential role in degradation of organic matter and recycling \+ lack membranes around their organelles \+ adapt to environmental changes by regulating gene expression. \+ don't express all their genes at once; instead, turn specific genes on or off as needed. This helps conserve energy and resources. **Genes vs Gene Expression** \+ bacteria have no nucleus, transcription and translation can occur in the same space \+ A single bacterial cell has somewhere between 2500 to 6000 genes, depending on the size of its genome. \+ Gene expression is regulated \+ Individual bacteria respond to environmental change by regulating their gene expression \+ Escherichia coli is a type of bacterium that lives in the human colon. E. coli can: - compete for nutrients with other bacteria - survive in many different environments - tune its metabolism to changes in the environment and different food sources **Molecular anatomy of a gene** \+ A gene has two parts: coding region, and a promoter (control region) \+ Bacterial transcription is regulated by a single RNA polymerase \+ RNA pol - 5 core subunits and a regulatory sigma subunit \+ Sigma subunit required for correct initiation of transcription **The Operon** \+ is a unit of genetic function, consists of a coordinately regulated cluster of genes with a related function \+ In bacteria, genes are often clustered into operons, composed of - A promoter - An operator, an "on-off" switch - Genes for proteins that work together \+ All the genes within an operon can be switched "on" and "off" by regulatory proteins + Structure: - Promoter: specific DNA sequence recognized by RNA polymerase. RNA polymerase binds to the promoter and transcription is initiated. - Operator: specific DNA sequence where corresponding regulatory proteins bind. This regulator-operator complex can 'turn a gene on' or 'off' by interfering with RNA polymerase activity **Tryptophan synthesis -- Trp operon repressible regulation** \+ 5 genes encode the 3 enzymes required for tryptophan synthesis. Tryptophan inhibits both an enzyme in the pathway and the expression of the genes encoding the enzymes. Tryptophan absent, repressor inactive, operon 'on' Tryptophan present, repressor now active, operon not transcribed **Co-ordinate control of Trp Operon** \+ By default, the trp operon is on and the genes for tryptophan synthesis are transcribed \+ When tryptophan is present, it binds to the trp repressor protein, which turns the operon off \+ The repressor is active only in the presence of its corepressor tryptophan; thus, the trp operon is turned off (repressed) if tryptophan levels are high **Gene regulation in eukaryotes** \+ Every cell in a eukaryote contains the same DNA \+ Not all genes are required at all times in all cell types and under different environmental conditions \+ Regulation of gene expression can occur at: chromatin remodeling, transcription, RNA processing, mRNA stability, translation, post-translational levels \+ The various levels of regulation are not mutually exclusive (for a given gene) **Chromatin regulation (chromatin remodeling)** \+ Histone structure can be modified by covalent attachment of various functional groups (acetyl, methyl, phosphate\... Generally: - histone acetylation is associated with active chromatin - histone and especially DNA methylation (cytosines, methyl-C) with inactive genes. \+ Eg: In some cases, cancer cells' tumor suppressor genes are inappropriately repressed by methylation, and heterochromatin is activated by acetylation. **Transcriptional regulation** \+ Every gene contains several control switches (in eukaryotes): - basal promoter - required for binding of general transcription factors - These specify/recognize the transcription start site and recruit other proteins required for the initiation of transcription -- including RNA Polymerase \+ gene features - enhancers and distal promoter - DNA sequences (often short \ - reduces chromosome \# from diploid to haploid - by separating homologous chromosomes - Separation of chromatids (haploid, like mitosis) - separates chromatids - four haploid gametes per starting cell **Genetic Variation** \+ Homologous chromosomes segregate and the non-homologous chromosomes assort independently during gamete formation \+ Each homologous chromosome contains the same genes - but (most likely) different allelic variants at each locus -\ alleles segregate because the 2 homologous chromosomes that carry them segregate in meiosis I \+ By crossover. Recombination events (crossovers) occur at pachytene (a stage in Prophase I of Meiosis I) at different sites along chromosomes. Some sites, so-called \"hotspots,\" are used more often than other sites. \+ "Crossing over" occurs during meiosis I \+ Genes linked on chromosomes \+ Linkage broken by "crossing over" - Ave. 2-3 crossover events / chromosome pair - mixes paternal and maternal regions between homologous chromosomes - new combinations of alleles on a chromosome \+ Between individuals in any sexually reproducing diploid population, results from: - Mutation -- new alleles - Independent assortment of homologous chromosome pairs (in meiosis) -- different combinations of parental chromosomes in different gametes - Recombination (crossing over) (in meiosis I) -- new combinations of alleles on chromosomes - Fusion of gametes (in fertilization) \+ Non-disjunction of homologous chromosomes (Meiosis I) or sister-chromatids (Meiosis II) - Chromosomes sometimes fail to separate properly during meiosis I or II - Gametes +/- 1 chromosome - Zygote will be aneuploid (2n +/- 1) (often lethal) **Summary** \+ Sexual reproduction involves the production of gametes by meiosis \+ Meiosis reduces the genetic material in gametes to 1n \+ Sexual reproduction includes many features that result in genetic variation 10/9 PRINCIPLES OF INHERITANCE (MENDEL'S LAWS OF GENETICS) **Gregor Mendel: Father of Genetics** **Traits in Pea Plants** Pea plants have several characters that can take two forms. Mendel looked at how they were inherited.  **Mendel\'s Methods** \+ P - Parents from two 'pure breeding' lines are crossed \+ F1 - First filial generation: phenotype scored then self-fertilised \+ F2 - second generation: phenotype scored \+ Also made 'test crosses' -- F1 x P **Monohybrid (single trait) Crosses** \+ Mendel noticed: - one trait lost in F1 - reappeared in F2 - 3:1 ratio in F2 - reciprocal cross gave similar results - other characters gave similar results \+ Mendel concluded: - inheritance is particulate - 2 copies of heritable factor - one trait is dominant  A white text on a white background Description automatically generated **Mendel\'s conclusions** 1. a\. Inheritance is particulate ('heritable factors'= genes; a word coined by Danish plant breeder Wilhelm Johannsen in 1909) b\. Alternative versions of genes account for variations in inherited characters (different alleles confer different traits of the same character) 2. a\. Organisms inherit 2 alleles for each character, one from each parent (peas are diploid) b\. Only 1 allele is passed on to gamete (gamete is haploid) 3\. If the 2 alleles differ, one may be dominant (other recessive) **Mendelian genetics works in all eukaryotes** **Inferring genotype from phenotype - using Mendel's laws** \+ Test cross 1\. Used to determine the genotype conferring a dominant phenotype 2\. Cross the individual in question to a known homozygous recessive **What Mendel observed with two traits** \+ Dihybrid cross  A diagram of a cell division Description automatically generated  with inheritance of two independent traits - For genes on separate chromosomes - Each allele pair shows independent segregation - F1 produces 4 gamete genotypes - F2 shows 9:3:3:1 phenotypes **Mendel's Principles** \+ Segregation (Mendel's First Principle): The two alleles separate from each other into the gametes (due to segregation of homologous chromosomes that carry them) \+ Independent assortment (Mendel's Second Principle): Genes segregate independently when gametes are formed (due to independent assortment of non-homologous chromosomes) \+ Dominance: Phenotypes depend on inheritance of dominant and recessive alleles **Summary** - Mendel demonstrated the principle of segregation and independent assortment - Punnett squares can be used to predict the results of a cross and to state the phenotypic and genotypic ratios of the F2 generation - A test cross can be used to determine genotype