Eukaryotic Gene regulation

We started with a brief detour to talk about antibody varition. Figs 17-22, 23 and 24 in your book. What is interesting is that it is an example of DNA itself being rearranged by mitotic crossing over, to produce variation in IgG genes. By randomly mixing and matching segments of the gene, it can produce huge numbers of variants. But each B cell produces only one kind.

Drosophila development

• Drosophila is the best studied animal in terms of the genetics of development. But the general principles are basic to almost all eukaryotes.
• Formation of gradients
• Formation of segments (threshold effects)
• Interactions among overlapping signals

Much of what we know about genes for development comes from a huge search for mutants, where they identified the major classes of mutants. Three main classes:

• maternal genes
• segmentation genes (gap genes, pair-rule genes and segment polarity genes)
• homeotic genes

General Rules

• Specify broad patterns first (body axis, etc)
• Early genes affect expression of later genes
• Interactions (+ and -) among genes specify fine-scale patterns
• Combinatorial control

Maternal genes

• "Bicoid" gene: expressed in maternal (oocyte) tissue.
• mRNA are at one end of cell (head)
• Bicoid protein diffuses through the cell. Creates a gradient of protein content, head to tail
• Bicoid mutants have tails at both ends
• Transcription factor for head genes and translation repressor of caudal
• "Nanos" is another maternal gene that creates the opposite gradient

Gap genes

• Gap genes are zygotic
• Gap Mutants have deletions of several segments
• Example: Hunchback
• • Responds to bicoid signal
  • Expressed in front section of embryo
  • controls other gap genes

Pair Rule genes

• Result in deletion of every other segment
• • Even-skipped
  • Fushi-tarazu

Segment polarity genes

• Create mirror image parts of segments
• • engrailed
  • gooseberry

See these genes in action

Go to the section on "processes" and then "pattern formation"

We looked at several interactive figures that show interactions and expression patterns of the various genes. Explore those interactive graphics to help yourself understand the regulatory networks.

Homeotic Genes

Bithorax complex

• Huge region of DNA; only 3 transcription units (ubx, abdA, abdB)
• Lots of upstream regulators (responding to various developmental signals like bicoid or hunchback)

Homeobox

• All of the homeotic genes have a conserved sequence of amino acids, the homeobox
• 8 hox genes in Drosophila (lab, pb, Dfd, Scr, Antp, Ubx, abdA and AbdB)
• Homeobox sequence binds DNA (8 bp)
• • Helix-turn-helix structure
  • Act as transcription regulator
• Also found in mammals, with similar gene effects and gene order.

I showed a figure that highlights the conserved anterior/posterior order of gene expression of these genes in flies and mice.

Flower development

We barely had time to talk about flower development. The basic processes of pattern formation: signaling cascade, positive and negative feedback loops, major genes that act as transcription factors, etc. are basically the same in plants and animals.

Here is what I would have said:

• Plants have more flexible develoment than animals
• Flowers do have deterministic development
• 4 whorls: Sepal, petal, stamens, carpel
• Controlled by overlapping gradients of gene expression.
• Many are MADS box genes (like homeobox, they bind DNA and are transcription factors)

3 main classes of mutants:

1. Meristem identity mutants: no floral meristem mutant: "leafy" in Arabidopsis
2. mutants that affect symmetry of flowers, bilateral ---> radial
3. Organ identity mutants (i.e. wrong organ at wrong place) (Homeotic mutants)

Expression of floral identity genes

• ABC model:
• 3 major patterning genes; Each affects two whorls
• A expressed in whorls 1,2
• B expressed in whorls 2,3
• C expressed in whorl s 3 and 4

Combinations of A,B, and C uniquely define each whorl.

(i.e. if both A and B are present, it must be whorl 2, etc).

Like all homeotic mutants, ddeletions of one of those pattern formation genes will produce incorrect floral organs. For example, deletions in A produces petals where stames should be and carpels where sepals should be.

Chapter 17 problems: