Genetics of Chromosomes:
Genome Organization



In Principle:

Chromosomes each comprise a single, continuous DNA molecule
       DNA is systematically packaged into chromosomes through several levels of coiling
       Most DNA does not code for proteins
       Non-coding DNA occurs in several classes



Chromosome architecture at the molecular level
             OR: Whatcha gonna do with all that junk inside your genes?

How is DNA packed into chromosomes?
        1o coiling of DNA helix
        2o coiling of DNA + histone core = nucleosome
              histone octamer: (H2A, H2B, H3, H4) x 2
              histone H1 + linker DNA
        3o coiling of core + linker forms Solenoid
                six H1 subunits
        4o coiling of solenoid loops to non-histone Scaffold

     scaffold supercoil chromatin thread chromosome

Fine-scale DNA structure of chromosomes [Chromosome 11 CSHL Animation]

     Protein-coding genes have introns, exons, promoters, enhancers
         'exon shuffling' hypothesis 
               exons as protein domains
               exon recombination occurs via transposable elements (Bio4241)
        Human genomes include ~20,050 protein-coding "genes" in <5% of DNA

     Telomeric DNA caps chromosomes (IG1 11.1 Research Briefing)

        may limit lifespan of cells in vitro and in vivo (aging) [Nobel Prize, 2009]

     Repetitive DNA accounts for >>50% of human genome, within and between coding gene loci
                Repeats may be dispersed or tandem
        Tandem repeats - multiple copies arranged end-to-end
            satellite DNA - variable [G+C] content
            NORs (nucleolus-organizer regions) comprise multiple rDNA genes
                    5S, 18S & 28S rRNA gene clusters
                     multiple rDNA genes allow more efficient production of rRNA
            VNTRs (variable number of tandem repeats)
                        micro- & minisatellites - 2 or 4~10bp repeats

        Dispersed repeats -  multiple copies scattered throughout chromosomes
            SINEs (short interspersed elements) may occur within introns
                    Alu family200 ~ 300 bp x 105 copies
                    Alphoid family - centromeric heterochromatin, 170 bp x ~103 copies
            LINEs (long interspersed elements) occur between genes
                    LI family - 6,400 bp x 104 copies


All text material ©2016 by Steven M. Carr