Controlling

 Gene  Expression  
 

Understand  how  cells  become  specialized  through  differential  gene  expression,  producing  active  mRNA,  leading  to  the  
synthesis  of  proteins  which,  in  turn,  control  cell  processes  or  determine  cell  structure  in  animals  and  plants  

The zygote and its very early descendants are totipotent - these cells have the potential to develop into a
complete organism.

Totipotency is common in plants, but is uncommon in animals after the 2-4 cell stage. As development
proceeds, the developmental potential of individual cells decreases until their fate is determined.

The determination of different cell types (cell fates) involves progressive restrictions in their developmental
potentials (The developmental potential, or potency, of a cell describes the range of different cell types it
CAN become).

Differentiation follows determination, as the cell elaborates a cell-specific developmental program.

Differentiation results in the presence of cell types that have clear-cut identities, such as muscle cells, nerve
cells, and skin cells.

Differentiation results from differential gene expression: The specific components of a given cell provide its
special characteristics. These components are either synthesized by proteins, or are themselves proteins. By
expressing different subsets of genes, two cells contain different subsets of gene products (proteins).
 
How  cells  become  specialized  through  differential  gene  expression?  

1)   All stem cells contain the same genes, but not all of them get expressed.
2)   under right conditions / stimuli some genes are activated and others inactivated this is brought about
by specific transcription factors getting activated.
3)   These transcription factors bind to the promoter region and form transcription initiation complex.
4)   RNA polymerase binds to this complex and the gene gets transcribed.
5)   mRNA is only transcribed from active genes.
6)   mRNA from active genes is then translated into proteins
7)   Proteins modify the cell- determine cell structure and control cell processes- activated more genes
8)   Permanent changes to cell by proteins cause the cell to become specialized (differentiate) changes
are difficult to reverse so stay like that.
 

understand  how  one  gene  can  give  rise  to  more  than  one  protein  through  post-­‐transcriptional  changes  to  messenger  
RNA  (mRNA)  

1.   After the mRNA is formed during transcription, it goes trough post-transcription modification
(spicing).
2.   The introns are removed and exons are put together by enzymes spliceosomes.
3.   The order in which the exons are joined can vary resulting in different types of mRNA molecules to
be formed from the same pre m RNA.
4.   These mRNAs when translated produce different proteins.

Post-­‐translation  control:  

Further modification of proteins takes place after it is made. A protein may remain intact or may be
shortened by enzymes to give a variety of proteins.
Epigenetics:  

Define Epigenetics: The study of changes in organisms caused by modification of gene expression rather
than alteration of the genetic code itself.

Example: mRNA splicing, Protein modification are forms of epigenetics.

Many times the environment also plays an important role in epigenetics, i.e., the environmental stimuli can
initiate

i.   DNA methylation
ii.   Histone modification
iii.   Non-coding RNA
To produce different phenotypes.

DNA  methylation:  

•   DNA methylation is a process by which methyl groups are added to the DNA molecule.
•   The addition of methyl group always occurs at the site where cytosine occurs next to guanine in the
DNA chain.
•   Addition of methyl group happens with the help of enzyme DNA methyltransferase.
•   Methylation can change the activity of a DNA segment without changing the sequence.
•   When located in a gene promoter, DNA methylation typically acts to repress/silences
gene transcription.

In mammals DNA methylation is essential for normal development and is associated with a number of key
processes including genomic imprinting, X-chromosome inactivation, repression of transposable
elements, aging, and carcinogenesis.

NOTE: Demethylation also plays an important role as it activates a gene.

Histone  modification:  

A histone modification is a covalent post-translational modification (PTM) to histone proteins which

includes methylation, phosphorylation, acetylation. The PTMs made to histones can impact gene
expression by altering chromatin structure.
When the chromatin is densely supercoiled and condensed, the genes are not available to be copied to
make protein. This is known as heterochromatin.

Histone  Acetylation  

Histone acetylation occurs by the enzymatic addition of an acetyl group (COCH3) from acetyl coenzyme A
to one of the lysine molecules in the histones.

This addition opens the structure of chromatin allowing the genes to be transcribed.

Histone  Methylation  

Histone methylation is defined as the transfer of one, two, or three methyl groups from S-adenosyl-L-
methionine to lysine or arginine residues of histone proteins by histone methyltransferase (HMTs).

HMTs control or regulate DNA methylation through chromatin-dependent transcriptional repression or

activation.
 Non-coding RNA.
A non-coding RNA (ncRNA) is a functional RNA molecule that is transcribed from DNA but not translated
into proteins.

About 90% of the human genome is transcribe into mRNA, but only 2% of those RNA molecules code for
proteins. Most of the ncRNA are used to silence genes and chromosomes.

In female one X chromosome is inactivated randomly (supercoiled), this is done mostly by ncRNA. This
results in X-chromosome inavtivation.

Genetics  
∗ Homologous  chromosomes  are  a  pair  of  chromosomes  in  a  diploid  cell  that  have  the  same  structure  as  each  
other,  with  the  same  genes  (but  not  necessarily  the  same  alleles  of  those  genes)  at  the  same  loci,  and  that  pair  
together  to  form  a  bivalent  during  the  first  division  of  meiosis.      
•   There  are  22  matching  chromosomes  in  humans  (homologous  chromosomes)  –  autosomes  –  and  a  non-­‐
matching  pair  labelled  X  and  Y  (sex  chromosomes);  two  sets  of  23  chromosomes  –  one  set  of  23  from  
the  father  and  one  set  of  23  from  the  mother    
*  A  gene  is  a  length  of  DNA  that  codes  for  a  particular  protein  or  polypeptide    
*  An  allele  is  a  particular  variety  of  a  gene    
•   A  locus  is  the  position  at  which  a  particular  gene  is  found  on  a  particular  chromosome;  the  same  gene  is  
always  found  at  the  same  locus    
*  Diploid  cell:  one  that  possesses  two  complete  sets  of  chromosomes;  the  abbreviation  for  diploid  is  2n    
*  Haploid  cell:  one  that  possesses  one  complete  set  of  chromosomes;  the  abbreviation  for  haploid  is  n  
-­‐   Without  halving  the  number  of  chromosomes  into  haploid  gametes  (meiosis  –  reduction  division),  it  
would  double  every  generation    
•   A  genotype  is  the  alleles  possessed  by  an  organism    
•   Homozygous  means  having  two  identical  alleles  of  a  gene  (e.g.  HbAHbA)    
•   Heterozygous  means  having  two  different  alleles  of  a  gene  (e.g.  HbAHbS)    
 
Genotype  affects  phenotype:    
Ø HbSHbS:  coding  for  the  production  of  the  sickle  cell  -­‐globin  polypeptide,  sickle  cell  anaemia    
Ø HbAHbA:  coding  for  the  normal  -­‐globin  polypeptide    
Ø HbAHbS:  Half  of  the  person’s  Hb  will  be  normal,  and  half  will  be  sickle  cell  Hb  -­‐  sickle  cell  trait  –  can  be  
referred  to  as  ‘carriers’  –  they  have  enough  normal  haemoglobin  to  carry  enough  oxygen,  and  so  will  have  no  
problems  at  all  and  immune  to  malaria    
 
An  organism’s  phenotype  is  its  characteristics,  often  resulting  from  an  interaction  between  its  genotype  and  its  
environment    
 
During  every  fertilisation,  either  an  HbA  sperm  or  an  HbS  sperm  may  fertilize  either  an  HbA  egg  or  an  HbS  egg.  
The  possible  results  can  be  shown  like  this:    

Monohybrid  crosses    

 
Genetic  diagram  of  flower  colour  in  snapdragons  (Antirrhinum)  -­‐  codominant:    
ØOne  of  the  genes  for  flower  colour  has  two  alleles,  namely  CR,  which  gives  red  flowers,  and  CW,  which  gives  
white  flowers.  The  phenotypes  produced  by  each  genotype  are: