Genetics and Genomics Pdf for Masters (University Classes) Best notes, Study notes of Biological Sciences

Download Genetics and Genomics Pdf for Masters (University Classes) Best notes and more Study notes Biological Sciences in PDF only on Docsity! Genome Structure Kinetics and Components Genome • The genome is all the DNA in a cell. – All the DNA on all the chromosomes – Includes genes, intergenic sequences, repeats • Specifically, it is all the DNA in an organelle. • Eukaryotes can have 2-3 genomes – Nuclear genome – Mitochondrial genome – Plastid genome • If not specified, “genome” usually refers to the nuclear genome. Components of the human Genome • Human genome has 3.2 billion base pairs of DNA • About 3% codes for proteins • About 40-50% is repetitive, made by (retro)transposition • What is the function of the remaining 50%? The Genomics Revolution • Know (close to) all the genes in a genome, and the sequence of the proteins they encode. • BIOLOGY HAS BECOME A FINITE SCIENCE – Hypotheses have to conform to what is present, not what you could imagine could happen. • No longer look at just individual genes – Examine whole genomes or systems of genes Genomics, Genetics and Biochemistry • Genetics: study of inherited phenotypes • Genomics: study of genomes • Biochemistry: study of the chemistry of living organisms and/or cells • Revolution lauched by full genome sequencing – Many biological problems now have finite (albeit complex) solutions. – New era will see an even greater interaction among these three disciplines Much DNA in large genomes is non-coding • Complex genomes have roughly 10x to 30x more DNA than is required to encode all the RNAs or proteins in the organism. • Contributors to the non-coding DNA include: – Introns in genes – Regulatory elements of genes – Multiple copies of genes, including pseudogenes – Intergenic sequences – Interspersed repeats Distinct components in complex genomes • Highly repeated DNA – R (repetition frequency) >100,000 – Almost no information, low complexity • Moderately repeated DNA – 10<R<10,000 – Little information, moderate complexity • “Single copy” DNA – R=1 or 2 – Much information, high complexity Reassociation kinetics measure sequence complexity Less complex DNA renatures faster, #2 DNA 1 DNA 2 DNA 3 ab cdefghijklmnopqrstuv izyajczkblqfreighttrainrunninsofastelizabethcottonqwf tzxvbifyoudontbelieveimleavingyoujustcountthedaysi mgonerxcvwpowentdowntothecrossroadstriedtocatch ariderobertjohnsonpzvmwcomeonhomeintomykitche ntrad ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab ab etc. cdefghijklmnopqrstuv cdefghijklmnopqrstuv cdefghijklmnopqrstuv Molar concentration of each sequence: 150 microM 15 microM 1.5 microM Relative rates of reassociation: 100 10 1 For an equal mass/vol: Equations describing renaturation − dC dt = kC 2 or dC C 2 = − kdt dC C 2 0 t ∫ = − k dt 0 t ∫ − 1 C 0 t = − kt 0 t 1 C − 1 C 0 = kt C C 0 = 1 1 + kC 0 t Let C = concentration of single-stranded DNA at time t (expressed as moles of nucleotides per liter). The rate of loss of single-stranded (ss) DNA during renaturation is given by the following expression for a second-order rate process: Solving the differential equation yields: Time required for half-renaturation is directly proportional to sequence complexity C 0 t 1 2 α N L For a renaturation measurement, one usually shears DNA to a constant fragment length L (e.g. 400 bp). Then L is no longer a variable, and C 0 t 1 2 α N N unknown N standard = C 0 t 1 2 unknown C 0 t 1 2 stαndαrd E.g. E. coli N = 4.639 x 106 bp (4) (5) (6) Almost all transposable elements in mammals fall into one of four classes Short interspersed repetitive elements: SINEs • Example: Alu repeats – Most abundant repeated DNA in primates – Short, about 300 bp – About 1 million copies – Likely derived from the gene for 7SL RNA – Cause new mutations in humans • They are retrotranposons – DNA segments that move via an RNA intermediate. • MIRs: Mammalian interspersed repeats – SINES found in all mammals • Analogous short retrotransposons found in genomes of all vertebrates. Long interspersed repetitive elements: LINEs • Moderately abundant, long repeats – LINE1 family: most abundant – Up to 7000 bp long – About 50,000 copies • Retrotransposons – Encode reverse transcriptase and other enzymes required for transposition – No long terminal repeats (LTRs) • Cause new mutations in humans • Homologous repeats found in all mammals and many other animals