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BERK OFFICE HOURS FOR MIMG 132: Mon 2:30-3:30 Wed 1:30-2:30 359 Boyer Hall The Molecular Structure of Genes and Chromosomes Fig. 21-1 Chromatid Fig. 21-35 Centromere Fig. 21-1 Chromatid Centromere Fig. 10-3 ~ 1/2 of human genes are solitary genes, like the SUR2 gene. There is only one gene of similar sequence in the haploid genome. Comparing the sequence of the human and mouse SUR2 genes, the exons are >90% identical, but the introns are <10% identical. SUR2 gene: exon intron 40 kb In contrast, the globin genes are members of a gene family. The -globin genes on chromosome 11 have exons that are >90% identical. They are also >80% identical to the -globin genes on another chromosome. ~1/2 of all human protein coding genes are duplicated, or members of a gene family (>2 closely related genes). Fig. 10-3 How did the duplicated genes arise? Fig. 10-3 Gene duplication by unequal crossing-over between homologous repeats: Paternal chromosome Fig. 10-4 Maternal chromosome Fig. 21-34 Fig. 10-34 Gene duplication by unequal crossing-over between homologous repeats: Paternal chromosome Fig. 10-4 Maternal chromosome How did the duplicated genes arise? Through gene duplication as a result of unequal crossingover between homologous chromosomes during meiosis. Fig. 10-3 Repititious DNA Simple sequence DNA ~3% of human DNA (total protein coding DNA <2%) Tandem repeats of sequences 1 to ~500 bp in length. Commonly called “satellite DNA” Micro-satellites: most 1-4 bp in length tandemly repeated in regions up to 150 bp in length. Thought to have accumulated during rare mistakes in DNA synthesis when the nascent daughter strand “slipped” along the parental template strand so that additional bases were inserted into the daughter strand. Nascent daughter strand 5’ NNNNNNNNCAGCAGCAGCAGCAG 3’ NNNNNNNNGACGACGACGACGACGACGACGACNNNNN 5’ Template strand 5’ NNNNNNNNCAGCAGCAGCAGCAG 3’ NNNNNNNNGACGACGACGACGACGACGACGACNNNNN 5’ Daughter strand “slips” backward GC A A C G 5’ NNNNNNNNCAGCAG CAG 3’ NNNNNNNNGACGACGACGACGACGACGACGACNNNNN 5’ DNA replication GC continues A A C G 5’ NNNNNNNNCAGCAG CAGCAGCAGCAGCAGNN 3’ NNNNNNNNGACGACGACGACGACGACGACGACNNNNN 5’ Differences in the number of repeats of a microsatellite sequence in the DNA of different individuals arise through unequal crossing over between chromosomes during meiosis. Fig. 10-6 “DNA fingerprinting” depends on differences between every individual in the number of tandem repeats of specific types of simple sequence DNA that occur in stretches of 500 bp--20 kb, called “minisatellite” sequences. These differences in the number of tandem repeats of simple sequence DNA result from “unequal crossing-over during recombination between homologous chromosomes during meiosis. Fig. 10-7 a minisatellite l33.6; b l33.15; c l33.5 DNA fingerprinting by PCR using primers that bind to the single copy sequences that flank “minisatellite” repeats. Most simple sequence DNA is composed of repeats of 14-500 bp tandemly repeated in stretches of 20100 kb. Most of these long simple sequence DNAs are found at centromeres of chromosomes and telomeres where they are thought to participate in the structure of these specialized regions of chromosomes. Fig. 10-5 The most common type of repititious DNA in multicellular organisms (accounting for ~ half of human DNA) is called “interspersed repeats” (also known as ‘moderately repeated DNA’ and ‘intermediate-repeat DNA’) These do not occur in tandem arrays, but rather individual copies of the same, or nearly the same sequence of ~100 bp to ~10 kb found at tens of thousands to millions of different positions on each of the chromosomes. These resulted from repeated insertions of transposons into new sites during the evolution of modern organisms. (Or to the action of enzymes encoded by transposons on other genomic sequences.) Fig. 10-3 Fig. 10-3 Fig. 4-15 Exon duplication by unequal crossing over between homologous repeated sequences on either side of an exon. exon n Multimerization of exons by unequal crossing over between homologous exons: exon n exon n+1 + Recombinant chromosomes Multimerization of exons by unequal crossing over between homologous repeats: L1 exon n exon n+1 + Recombinant chromosomes Fig. 4-15