1LECTURE 12: INSIGHTS FROM GENOME SEQUENCINGRead 337-345; p327 (ortholog)Table 10.1Fig. 10.14; 10. 15; 10.18, 10.192Genome sequencing changed the practice ofbiology, genetics and genomics1. High density molecular markers -facilitate gene mapping and cloning of disease genes -disease diagnosis, prevention, and cure -forensic, identity, defense etc.2. Global insights into genome organization and structure-how much repeats/transposons3. Comparative genomics/evolutionary insightsortholog vs. paralog4. Facilitate understanding related genomes5. Facilitate gene expression and functional analyses -discover noncoding RNA/RNA splicing/protein coding3Comparison of total gene numbers in sequencedgenomes:Near constant number of genes in all genomes irrespectiveof genome sizes25,000 Arabidopsis20-25,000 human19,099 in C. elegans13,600 in DrosophilaSmaller than originally expectedHuman genome thought to have 100,000 genesNow thought to be closer to 20,000–25,000 genesInsights from genome sequencing4Selective expansion of genes (paralogs)Many new functions arise in gene expression -Use old genes in new ways - Alternative splicing–Roundworm, C. elegans, has a large number of nuclearreceptor genes–Drosophila has a large number of zinc-fingertranscription factors–Plants have no G-protein-coupled receptorsDifferent shuffling of discrete functional units(ie. protein domains)-Each protein contains different combinations of proteindomains. Protein composition may change with evolution5Fig. 10.19Olfactory gene families56Fig. 10.1467What is the difference between man and ape?• Man and chimpanzee have agenomewide similarity ofgreater than 95%.• What accounts for differencesbetween species?• Recent study suggests thatdifferences between species aredue to specific gene expressiondifferences– Striking differences found onlyin brainFrom Genomics by Benfey and Protopapas 20058The C-value paradox The bigger a genome, the more repetitive DNAArabidopsis: 1X 105 kb (14%) Tomato: 1X 106 kb (15-20%); Mung Bean: 4.5X105 kb (30%)Pea: 4.1X 106 kb (70%)Wheat, Corn 107 kb (60-80%)-Adh1 gene in maize:9Comparative genomics• Synteny: genes that are in the same relative position on twodifferent chromosomes• Genetic and physical maps compared between species– Or between chromosomes of the same species• Closely related species generally have similar order of geneson chromosomes• Synteny can be used to identify genes in one species basedon map position in another10Synteny: Colinearity of loci (genes) among different plant speciesi.e. Revolutionarily conserved organization and arrangement of single copy genes20 of the 54 genes in a 340 kb stretch of the rice genome (top) retain the same order in five different 80-200 kb regions of Arabidopsis genomegenes on different strandsinterspersed, unrelated genes11Synteny of Grass genomes• Synteny among cropgenomes: rice, maize, andwheat• Rice is smallest genome–incenter• Wheat is largestgenome–outer circle• Genes found in similarplaces on chromosomes areindicatedFrom Genomics by Benfey and Protopapas 200512Synteny of sequenced genomes• When sequences from mouse and human genomes are compared, wefind regions of remarkable synteny• Genes are in almost identical order for long stretches along thechromosomeHumanChr 14MouseChr 14From Genomics by Benfey and Protopapas 200513Mouse–human syntenyFig. 10.1514Orthologs and Paralogs• When comparing sequence from different genomes, mustdistinguish between two types of closely relatedsequences– Orthologs are genes found in two species that had acommon ancestor– Paralogs are genes found in the same species thatwere created through gene duplication events15Arabidopsis thaliana (www.arabidopsis.org) Genome sequence completed in 2000, published in 5 installmentSee “Arabidopsis Genome Intiative, 2000 (pdf)”-115 Mb, 25,500 predicted genes, -Whole genome duplication 2X followed by extensive shuffling of chromosomal regions and gene loss-The majority of the genes can be assigned to just 11,000 families, which might represent the minimal complexity or “toolkit” to support complex multicellularity. Animal and plant genomes might evolve from this toolkit-Distinctive features of plant genome: ~ 800 genes are of plastid decent ~10% genome are transposable elements ~ plant specific genes: Enzymes for cell wall biosynthesis, photosynthesis, secondary metabolitesPhotptrophic, gravitrophicTransport proteins for nutrient, ion, toxic compound, metabolites between cellsPathogen resistant genes16Human genome: 3200 Megabases20-40,000 genesProteome: The collective translation of the 30,000 predicted genes into proteins Gene families: 1200 92 or 7% are vertebrate-specific(involved in immunity, defense, nervous system)http://www.ncbi.nlm.nih.gov/genome/guide/human/Repeats in the human genome: = >50%Evidence of lateral gene transferMales have more than two fold mutation in meiosis over femaleDifferent human races are genetically a single raceAll living organisms evolve from a common ancestor17Repeats in the human genome = >50%45% = transposon derivedLINES (Long interspersed elements) SINES (Short interspersed elements)LTR-retrovirusDNA transposonsPseudogenesSimple sequence repeatsSegment duplication (10-300 kb) ~ >5%Centromere and telomere repeats18Fig.
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