Download Recombination between homologous chromosomes

Homologous recombination -­ Recombination between homologous chromosomes -­ Paternal and maternal chromosomes line up -­ Chiasmata (a point at which paired chromosomes remain in contact during the first metaphase of meiosis, and at which crossing over and exchange of genetic material occur between the strands) form at regions of homology -­ Segments of DNA are exchanged When things go wrong – terminology -­ Diploid = having two sets of chromosomes -­ Haploid = having one set of chromosomes -­ Polyploid = having more than two complete sets of chromosomes -­ Euploid = having an equal number of all the chromosomes of the haploid set -­ Aneuploid = having a different number of chromosomes than is usual -­ Aneuploidy occurs when there is an error in meiosis o Most cases lead to miscarriage o 1 in 160 babies have aneuploidy o most commonly trisomy 21, 18 and 13 Origins of genetic variation -­ The behaviour of chromosomes during meiosis and fertilisation is responsible for most of the variation that arises in each generation -­ Three mechanisms contribute to genetic variation: o 1. Independent assortment of chromosomes o 2. Crossing over – shuffle DNA between maternal and paternal contribution o 3. Random fertilisation -­ Mutation also contributes, but is usually harmful Independent assortment of chromosomes -­ In independent assortment, each pair of chromosomes sorts maternal and paternal homologues into daughter cells independently of the other pairs -­ For humans (n = 23), there are more than 8 million possible combinations of chromosomes Crossing over -­ Produces recombinant chromosomes, combining genes inherited from each parent -­ Begins very early in prophase I, as homologous chromosomes pair up gene by gene (synapsis) -­ In crossing over, homologous portions of two non-­sister chromatids trade places -­ Crossing over contributes to genetic variation by combining DNA from two parents into a single chromosome Random fertilisation -­ Adds to genetic variation because any sperm can fuse with any ovum (unfertilised egg) -­ The fusion of two gametes (each with 8.4 million possible chromosome combinations from independent assortment) produces a zygote with any of the 70 trillion diploid combinations How are alleles separated during sexual reproduction? -­ Alleles are often generated from simple mutations -­ For example: Cystic Fibrosis (CF) o Involves mutant allele of a gene, CFTR, on chromosomes 7 o The ‘normal’ CFTR protein (wild type) controls the movement of chloride ions across the membranes of the cells in the gut, lungs, pancreas and liver o Mutant allele varies from normal allele by deletion of just one amino acid § Causes excess mucous production blocking ducts like bronchioles § Most patients die from lung infections o The allele that causes CF originates from a single amino acid deletion of the “normal” allele that controls cellular chloride channels Inheritance -­ CF is recessive -­ Need 2 copies of the mutant (i.e. homozygous for CF) allele before you get the symptoms of the disease -­ One copy of the normal gene (+) produces sufficient normal protein to make cells function normally so that heterozygotes (+/CF) are normal -­ If two parents that are normal heterozygotes reproduce, they can produce both affected (CF/CF) and non-­affected (+/CF or +/+) offspring Populations -­‐ Populations are individuals of a species that interbreed with each other, but not with individuals of the same species of another populations -­‐ Different populations, over time, become more genetically differentiated -­‐ Over very long periods of time, with no genetic exchange, they evolve into different species Gene Pool -­‐ The entire content of a population;; every allele -­‐ It is not practical to study the entire gene pool so we only look at specific alleles at a time Generation of new diversity -­‐ Mutations o Change in the DNA sequence o Caused by errors in DNA replication o Caused by mutagens (e.g. UV light, chemicals) that modify the DNA in a cell o Overwhelmingly, mutations are deleterious but some create alleles that increase fitness -­‐ Sexual reproduction o New combinations of alleles produced o Generated by recombining alleles during meiosis Hardy-­Weinberg Equilibrium -­‐ When allele and genotype frequencies remain constant from generation to generation, the population is not evolving -­‐ Only Mendelian segregation and recombination of alleles are a work -­‐ Previously we used Punnett squares to determine the genotypes of offspring in a genetic cross -­‐ Here, instead of using one cross, we consider the combination of alleles in all of the crosses in a population (genotype and allele frequencies) -­‐ Genotype (& allele) frequencies in the next generation must add up to 1 (100%) -­‐ The equation for Hardy-­Weinberg Equilibrium states that at a locus with two alleles, the three genotypes will appear in the following proportions -­‐ Hardy-­Weinberg approach: hypothetical population that is not evolving -­‐ BUT in real populations, the allele and genotype frequencies often change over tine -­‐ Such changes can occur when at least one of the following five conditions of Hardy-­Weinberg equilibrium is not met: -­‐ Departure from Hardy-­Weinberg conditions usually results in evolutionary change, which is common in natural populations Calculating frequencies -­‐ Genotype and allele frequencies are proportions -­‐ E.g. 3 dogs out of 5 pets – the proportion of dogs is 3/5 so the correct answer is either: 0.6 or 60% -­‐ Genotype frequency is the number of individuals with a specific genotype, divided by the number of total individuals -­‐ Allelic frequency is the number of a particular allele, divided by the total number of alleles in all individuals How many genotypes? -­‐ Two homologous chromosomes in a diploid organism, one from each parent > -­‐ One genotype per individual – in this case, heterozygous How many alleles? Two alleles – one per chromosome in every individual Terminology Chromatin = the DNA double helix in the cell nucleus packaged by special proteins called histones Chromatosome = a nucleosome with one bound linker histone Chromosome = thread like structure of nucleic acids and protein found in the nucleus of most living cells Chromosome territory = regions of the nucleus preferentially occupied by particular chromosomes Euchromatin = chromosome material which does not strain strongly except during cell division, it represents the major genes and is involved in transcription Heterochromatin = chromosome material of different density from normal (usually greater), in which activity of the genes is modified or suppressed Histone = group of basic proteins found in chromatin Karyotype = number and visual appearance of the chromosomes in the cell nuclei of an organism or species Nucleoid = irregularly shaped region within the cell of a prokaryote that contains all or most of the genetic material called genophore Nucleosome = structural unit of a eukaryotic chromosome, consisting of a length of DNA coiled around a core of histones Plasmid = genetic structure in a cell that can replicate independently of the chromosomes Silencing = the ability of a cell to prevent the expression of a certain gene Gene density = ratio of the number of genes per number of base pairs written in terms of (Mb) Genome = all information needed for growth and developments of an individual, every cell contains the same genome Operon = a stretch of DNA including promoter, operator and genes Promoter = region of DNA that initiates transcription of a particular gene Regulatory regions = controls when and where expression occurs for the protein coding region Open reading frame = part of the reading frame that has the potential to be translated Intron = non-­coding sections of an RNA transcript, or the DNA encoding it, that are spliced out before the RNA molecule is translated into a protein Exon = any part of a gene that will encode a part of the final mature RNA produced by the gene after introns have been removed by RNA splicing Elongation = addition of amino acids to the growing protein chain, order is specified by the sequence of codons in mRNA Initiation = initiation of translation occurs when mRNA, tRNA and an amino acid meet up inside the ribosome Termination = transcription terminator is a section of nucleic acid sequence that marks the end of a gene or operon in genomic DNA during transcription RNA polymerase = an enzyme that produces primary transcript RNA in cells TATA box = DNA sequence that indicates where a genetic sequence can be read and decoded Transcription = first step of gene expression, in which a particular segment of DNA is copied into RNA Transcription initiation complex = transcription factors and RNA polymerase form the transcription initiation complex Transcription start site = at the 5’ end of the gene sequence tRNA = transfer RNA, small RNA molecules that carry amino acids to the ribosome for polymerization into a polypeptide mRNA = messenger RNA, sub-­type of RNA, mRNA molecule carries a portion of the DNA code together parts of the cell for processing, created during transcription RNA = nucleic acid present in all living cells, acts as a messenger carrying instructions from DNA for controlling the synthesis of proteins Ribosomes = bind to mRNA and transfer RNA to synthesize polypeptides and proteins Watson-­Crick rule = dictated by specific hydrogen bonding patterns, Watson-­crick base pairs allow the DNA helix to maintain a regular helical structure that is subtly dependent on its nucleotide sequence Wobble = wobble base pair is a pairing between two nucleotides in RNA molecules that does not follow Watson-­crick base pair rules Primary structure = sequence of amino acids in a protein – determined by inherited genetic information Secondary structure = coils and folds result from hydrogen bonds between repeating constituents of the polypeptide backbone (coil called helix and folded structure called pleated sheet) Tertiary structure = determined by interactions between R groups, rather than interactions between backbone constituents Quarternary structure = results when two or more polypeptide chains form one macromolecule Microtubules = shaping the cell, guiding movement of organelles and separating chromosomes during cell division Intermediate filaments = support cell shape and fix organelles in place Microfilaments (actin filaments) = bear tension, resisting pulling forces within the cell Dynein arms = alternately grab, move and release the outer microtubules Protein cross-­links = limit sliding Cytoskeleton = network of fibres extending throughout the cytoplasm for structure and activities, anchoring organelles Peroxisomes = specialised metabolic compartments Nuclear envelope = surround the nucleus with a double membrane with multiple pores Endoplasmic reticulum = network of membranous tubules within the cytoplasm of a eukaryotic cell, usually has ribosomes attached, involved in protein and lipid synthesis (Rough = protein synthesis, smooth = lipid synthesis) Golgi apparatus = complex of vesicles and folded membranes within the cytoplasm, secretion and intracellular transport Lysosomes = digestive enzymes, digestion and waste removal of worn out organelles, food particles, viruses/bacteria Vacuoles = hold materials and wastes (central vacuole in plants) Mitochondria = produce energy currency of the cell – ATP Plasma membrane = selective barrier that allows sufficient passage of oxygen, nutrients and waste Ribosomes = protein synthesis Amphipathic = having both hydrophilic and hydrophobic parts Cytoskeleton = network of protein filaments and tubules, giving the cell shape and structure Fluid mosaic model = explains various observations regarding the structure of functional cell membranes