The developing hindbrain

Winning essays 2005

Sumayya Shahid of the Latymer School wrote the winning essay, 'If all the cells in the human body have the same DNA, why are there so many types of different kinds of cell?', and received the first prize of £100. The two runners up, who received £50 each, were:

As part of their prize the three winners also spent a day at NIMR, seeing some of the most interesting aspects of a research institute. Every entrant received a certificate recording their participation in the competition, and a copy of the latest Mill Hill Essays.

Read the winning essay

If all the cells in the human body have the same DNA, why are there so many types of different kinds of cell? by Sumayya Shahid of the Latymer School

The human body consists of many kinds of cells such as those in the skin, muscle, liver and brain. These cells vary greatly in structure and function, yet they all contain identical DNA. Information encoded in genes (segments of DNA) is transcribed by mRNA and translated to proteins – this is known as gene expression. Every cell needs different proteins for specific functions – however, if the DNA in every cell of the human body is the same why are cells so functionally diverse? What allows cells to become different (differentiate) or specialised (have a particular function)? The answer lies in the regulation of our gene expression. In fact not all the genes in a cell are “switched on” ready to be expressed1. Different genes are active in different cell types, producing the necessary proteins for the cell1. For example the gene for producing haemoglobin is only expressed in red blood cells, whilst the gene coding for insulin will be expressed in pancreatic cells alone. Cells produce different proteins according to their needs – they do not waste chemical energy producing proteins that will not be used2. This essay aims to look at how these gene expression is controlled, thus allowing body cells to differentiate and specialise despite having the same genome (genetic code).

Cell differentiation begins when a fertilised egg (zygote) divides repeatedly to for an embryo, with all daughter cells (cells produced from the original) having identical genomes. It is believed these unspecialised cells respond to chemical stimuli, which activate specific genes known as developmental control genes3. These code for the production of regulatory proteins. The proteins in turn control which genes are expressed (transcribed) or turned off in the cell, i.e. they determine what proteins a cell will produce and so determine its function, resulting in a differentiated cell3. The mechanism of these regulatory proteins is looked at later. Certain cells (stem cells) remain undifferentiated, but have the ability to differentiate into any organ type4. Scientists researching this phenomenon believe that stem cells, contained in the bone marrow (all with the same DNA) could be induced to form different tissues, composed of different cell types5. This would allow low cost, efficient regenerative medicine for replacing damaged tissue5. It can be seen that despite all cells having the same DNA, differentiation of cells can occur – it is basically dependent on which genes are expressed in the cells.

Gene expression is constantly occurring in the human body. However, at any one time the average cells is expressing only 1/3 of its available genes6. Control of gene expression occurs mainly at the transcriptional level6, as this is the first step towards manufacturing proteins needed by a cell. Certain regulatory proteins operate at this stage and determine which genes are to be activated, ready for transcription. During transcription mRNA (a mobile copy of a gene) is made from DNA. The process is initiated when the enzyme RNA polymerase, binds to a site on the DNA called a promoter sequence, usually adjacent to the gene that is to be transcribed2. However RNA polymerase cannot bind without assistance by a type of regulator protein known as transcription factors. These proteins are attracted to only certain promoter sequences, as they are specific, and then encourage the RNA polymerase to bind and begin transcribing2. By attaching to certain promoter sites, transcription factors activate certain genes, allowing them to be expressed2. Put simply, RNA polymerase requires transcription factors to know which promoter sites to bind to i.e. which genes are to be transcribed or expressed. It is clear therefore that transcription factors, along with promoter sequences are responsible for activating certain genes. They dictate which genes a cell will express, so which proteins are made, hence determining the type of cell it is.

Just as genes can be activated they can also be “switched off” by regulatory proteins called repressor proteins. These function by blocking a cell’s unneeded genes, hence inhibiting transcription7. For example brain cells do not need to make digestive enzymes, so the genes coding for these are “switched off”8. Repressor proteins bind to DNA sequences called silencers7. Upon doing so they can block promoter sites for certain genes so that RNA polymerase cannot bind, therefore the gene cannot be transcribed7. Another important mechanism for preventing gene expression is methylation. Unnecessary genes for a cell’s function can be tagged with a methyl group (CH3). The methyl tags provide a signal saying that the gene should not be expressed8. In effect the gene is switched off, therefore a cell does not produce unneeded proteins and can exist as a different, specialised cell. The effect of methylation is important in cloning technology. Cloning involves inserting a fully differentiated cell’s nucleus into an egg cell that has had its nucleus removed8. The problem is that inserted DNA is methylated according to the need of a fully differentiated adult cell. The DNA must be remethylated so that developmental genes become active8 and it can grow. Scientists have fund this difficult to achieve and this probably accounts for the low success rate in cloning8. Mechanisms such as repressor proteins, silencers and methylation show how different genes can be blocked in different cells. Therefore despite all cells having the same genome, they do not all produce the same proteins, consequently resulting in cells of different kinds.

It is evident that despite having identical genomes, different cells in the human body control which genes are being expressed. This may be through the use of regulatory proteins, DNA sequences and chemical tagging, which can assist or prevent RNA polymerase transcribing a gene. I think that the regulation of gene expression is extremely important in humans for cells to be able to perform the right functions. For example we do not need our brain cells to produce haemoglobin, which helps carry oxygen around in the blood. It is this control of gene expression, which is responsible for making cells different to one another allowing them to perform their functions efficiently.

References
  1. http://www.biology-online.org/3/1_genetic_control.htm (January 2004)
  2. http://www.esf.edu/efb/course/EFB325/lectures/expressi.htm (November 2004)
  3. http://www.sci.uidaho.edu/bionet/biol115/t8_cell_diff/lesson01/lesson1.htm (March 2004)
  4. Tom Strachan & Andrew P. Read (2004) Human Molecular Genetics 3 Garland Publishing
  5. Nowak, Rachel (2003) The sweet way to make cells do what you want New Scientist 2418
  6. Bruce Alberts et al. (1994) Molecular Biology of the Cell, 3rd edn Part II. Molecular genetics, Chapter 9
  7. http://web.indstate.edu/thcme/mwking/gene-regulation.html#top (October 2004)
  8. http://www.dnamethsoc.com (March 2004)

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