Organization of Human Genome (esp. non-protein coding genes)
  
   
highly condensed DNA (heterochromatin) is often not expressed &
    more loosely condensed DNA (euchromation) is expressed.

  
   
chemical modification via histones in genomic DNA can often REGULATES DNA's ACTION:

        
         ACYLATION (-COCH3) of histones (lys) unfolds chromatin     c7-fig 19.4*
      

             METHYLATION of nucleotides leads (often to C)
favors condensation
                                        
and leads to inactive DNA... once CH3 - passed generationally.

                                                                                                                                                                                                    
Twins show majors chromatin differences*
  

  Non-Coding Genes and Genome Structure:
  

         in prokaryotes:   DNA codes for proteins, tRNA, or rRNA  (avg. gene = 1,000np)
                                         non-coding DNA is mostly promoters; generally no introns

  

         in eukaryotes:     most DNA is non-coding (mostly introns)
                                         avg. gene is 27,000np         
c7 fig 19.14*
 

 

 

 

 

 

 
   summer 2007 - SKIP FOLLOWING....   
   non-protein coding DNA genome makeup
:

    
    largest portion of human genome is
Transposable Genetic Elements    
       
    2 types:
           1.  transposons (cut & paste) - 
c7-fig 19.16a*
                                   
a genetic element that moves by means of a DNA intermediate
           2.  retro-transposon (RNA intermediate) -
c7-fig 19.16b*
                                    move via a transcript of the retrotransposon DNA
         
                in humans one group of transposable genes is the Alu elements
                       
10% of human genome (1.4 million copies - some 500,000 Alu elements)
                                   each Alu element is about 300 n long with a poly-A tail, non-coding
                                        copy themselves & reinsert into genome randomly (like a genomic parasite)
                                        1 new insert per every 100-200 births         [figure
*]
                           5% of human alternatively spliced genes hold Alu pieces
   
                origins of Alu ? --> piece jumped into an intron --mutation--> created new 5' or 3' splice site
                                                    resulting in exon that was alternatively splice into mRNA
                                 Alu pieces are transcribed into RNA whose function is unknown
 

 

 

 

 

 

  next largest portion of Human Genome is short Repetitive DNA...
 

      15% of human genome is Repetitive DNA.
           
     ⅓  is large piece repeats (10K-300K np) often copied from 1 chromosome location
        3% is single DNA short sequence repeats of  --GTTAC--
                repeats sequences can be from 5n (short) yup to 500n
                most are located at teleomers and centromeres

  

 
next largest portion of Human Genome is Intronic DNA within genomic DNA...
  

 
    1.5% of Human genome is exonic DNA (i.e., some 25,000 genes)
                 
½ of exonic DNA is "traditional" single gene unique sequence DNA
     24.0% is intronic multigene family DNA...
             
  ex: identical repeats rDNA genes - tandem repeats of DNA coding for rRNA
                             advantage: can make millions of ribosomes, as needed, for protein synthesis
                                                 - mass production; primary transcript is processed
  c7 fig 19.17a*
                ex: non-identical repeats - globin genes --> a & β polypeptides of Hb
                            chromosome 16  holds 
α  gene family     c7 fig 19.17b*  different forms of globin genes
                            chromosome 11  holds 
β  gene family                   are expressed at different developmental stages.
                             
includes psuedogenes (non-functional nucleotides sequences
)
 
          possible origins of gene families --> c7 fig 19.19* mutation, transposition, duplication
    

 

 

 

 

 

 
   EXON Shuffling... can lead to significant genome rearrangement
(evolutionarily significant)
 
        exons are mixed and matched due to meiotic division errors
        occurs via unequal crossing over at non-sister transposable element sites  c7 fig 19.18
*

       
recall that proteins often have a modular architecture
               made up of discrete structural & functional regions called
domains
             
 different exons code for the different domains of a protein - c7 fig 17.12
*
  
     ex:  TPA (tissue plasmogen activator)  an extracellular protein that prevents blood clotting
                    protein has 4 domains - 3 each coded by different exon & 1 duplicate
                    each exon is also found in other proteins
                    origin may have been by exon shuffling - c7 fig 19.20
*

    
   - back
       

 

 

 

 

    In the largest study of its kind, [80 sets of identical twins, ranging in age from 3 to 74 years]
    researchers have shown that
35% of twin pairs have significant differences in DNA-methylation
   
and histone-modification profiles (Fraga et al, 2005).

M.F. Fraga et al, Epigenetic differences arise during the lifetime of monozygotic twins, Proc. Natl. Acad. Sci. 102: 10604-9.  July 26, 2005

 

 

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