6.1.3

• Homeobox gene sequences

  several of genes (large and ancient family of genes, the homeotic genes; involved in controlling anatomical development), contain homeobox sequences, sometimes called homeobox genes

  • each homeobox sequence is a stretch of 180 DNA base pairs (excluding introns) encoding a 60-amino acid sequence, homeodomain sequence
• Homeobox gene sequences 2

  • the homeodomain sequence can fold into a particular shape + bind to DNA, regulating the transcription of adjacent genes

  → these proteins are transcription factors ++ act within the cell nucleus

  • the shape that these homeodomain-containing proteins fold into is called H-T-H

  → consists of two alpha-helices (H) connected by one turn (T)

  • part of the homeodomain amino acid sequence recognises the TAAT sequence of the enhancer region (a region that initiates or enhances transcription) of a gene to be transcribed
• How Hox genes control body plan development in animals

  the Hox genes regulate the development of embryos along the anterior-posterior (head-tail) axis

  • they control which body parts grow where
  • if Hox genes are mutated, abnormalities can occur such as the antennae on the head of Drosophila developing as legs
  • hox genes are arranged in clusters + each cluster may contain up to 10 genes

  → in tetrapods (four-limbed vertebrates) including mammals + therefore humans, there are 4 clusters

  at some stage during revolution, the Hox clusters have been duplicated

  figure 2

  
• in early embryonic development, Hox genes are active + are expressed in order along the anterior-posterior axis of the developing embryo

  • the sequential + temporal (in time) order of the gene expressions corresponds to the sequential + temporal development of the various body parts, a phenomenon known as colinearity

  figure 3

  
• Hox genes encode homeodomain proteins that act in the nucleus as transcription factors + can switch on cascades of activation of other genes that promote mitotic cell division, apoptosis, cell migration + also help to regulate the cell cycle

  • Hox genes are similar across different classes of animals e.g. a fly can function properly with a chicken Hox gene inserted in place of its own
• How are the regulators regulated?

  Hox genes are regulated by other genes called gap genes + pair-rule genes

  • in turn, these genes are regulated by maternally supplied mRNA from egg cytoplasm
• Mitosis

  part of cell cycle that is regulated with help of homeobox + Hox genes, ensuring that each new daughter cell contain the full genome + clone of parent cells

  • during cell differentiation some of the genes in a particular type of cell are ‘switched off’ + not expressed

  → Leonard Hayflick showed that normal body cells divide a limited number of times (about 50 times - known as Hayflick constant)
• Apoptosis

  programmed cell death

  the sequence of events during apoptosis

  1. enzymes break down the cell cytoskeleton
  2. the cytoplasm becomes dense with tightly packed organelles
  3. cell surface membrane changes + small protrusions called blebs form
  4. chromatin condenses, the nuclear envelope breaks + DNA breaks into fragments
  5. the cell breaks into vesicles that are ingested by phagocytic cells, so that cell debris does not damage any other cells or tissues. The whole process happens quickly.

  
• Control of apoptosis

  many cell signals help to control apoptosis

  • some of these molecules may be released by cells when genes that are not involved in regulating the cell cycle + apoptosis respond to internal cell stimuli + external stimuli like stress
  • these signalling molecules include cytokines from cells of the immune system, hormones, growth factor + nitric oxide

  → nitric oxide can induce apoptosis by making the inner mitochondrial membrane more permeable to hydrogen ions + dissipating the proton gradient
• Control of apoptosis 2

  proteins are released into the cytoplasm where they bind to apoptosis inhibitor proteins, allowing apoptosis to occur
• Apoptosis + development

  apoptosis is an integral part of plant + animal tissue development

  • extensive proliferation of cell types is prevented by pruning through apoptosis, without release of any hydrolytic enzymes that could damage surrounding tissues
  • during limb development, apoptosis causes the digits to separate from each other

  → apoptosis removes ineffective or harmful T-lymphocytes during the development of the immune system
• Apoptosis + development 2

  in children aged between 8-14, 20-30 billion cells per day apoptose; in adults, about 50-70 million cells per day apoptose

  the rate of cells dying should equal the rate of cells produced by mitosis:

  • not enough apoptosis leads to tumour formation
  • too much apoptosis leads to cell loss + degeneration