How We Learned How Genes are Regulated! Pt. 3 Maddie Ostergaard

What this section is about ▪ How different cells become specialized ▪ Timing the expressions of genes ▪ The cell cycle ▪ How organisms adapt to inhibiting mutations

What determines the diversity of cells in the same organism? a)The type of DNA that is located in the nucleus of that particular cell a)The genes that are transcribed and translated in that cell

B! ▪ Nearly all somatic cells in multicellular organisms contain the same DNA content ▪ The diversification of tissues and organs is determined by the genes that are translated into proteins ▪ The set of genes expressed is determined by signals received by the cells and its activators and repressors ▪ The different types of genes – Housekeeping Genes: Genes expressed in all cell types ▪ Ex. Actin – Tissue-Specific Genes: Genes that are expressed in certain cell types only ▪ Ex. Hemoglobin

In what cells is hemoglobin synthesized? a) Erythrocytes a)Somatic cells a)Gametes a) Lymphocytes

A! ▪ Hemoglobin: Found in erythrocytes (or RBCs), this cell- specific protein is in charge of transporting O 2 and CO 2 throughout the body ▪ Different forms of hemoglobin are expressed during different stages of human development – See chart Hemoglobin Type Embryotic (< 8 weeks) ζ2ε2 α 2 ε 2 ζ 2 γ 2 Fetal (3-9 months) α 2 Υ 2 Adult (From birth) α2β2α2β2

Globin gene arrangement The order the genes are arranged in within the genome is the same organization as the order of expression during development

What regulates hemoglobin gene expression? ▪ There are many potential sites for gene regulation ▪ Scientists have studied this question through laboratory experiments and studies with mutated forms of the genes that might cause regulation ▪ In order to do this, scientists have had to understand the type of mutations that hemoglobin undergoes

Which type of mutations does hemoglobin undergo? a)Mutations within the parts of the hemoglobin genes b)Mutations outside of the coding regions (in regulatory genes)

Both! ▪ Mutations both in the hemoglobin genes and the surrounding genes have been evaluated – Scientists are particularly interested in genes that cause forms of the disease thalassemia ▪ One of the most promising finds was the hypersensitivity of the β- globin gene cluster ▪ The β-globin gene cluster has four sites that are extremely sensitive to degradation when treated with DNase ▪ Scientists predict that this is due to transcription factors binding to the cluster and altering the genes expressed

Gene Synchronization How different genes are timed to be expressed at the right time

What are the four stages of the cell cycle? ▪ No hints!

Coordinating different gene expressions ▪ Movement from each phase is either restricted or enabled by the threshold levels and signals of the cell ▪ Cyclin proteins: Proteins that govern the cell cycle by peaking in concentration at specific times and enabling the cell to move on to the next phase – Labeled A-E ▪ Repairing DNA before replication: – Checkpoint Genes: DNA repair proteins that prevent cells from entering the S phase of the cell cycle before DNA is repaired ▪ Rad9: Discovered in the 1970s by Leland Hartwell while he was studying the cell division cycle using mutated yeast – The rad9 mutant carried on with cell division despite ionizing radiation that prevented the DNA replication of other yeast cells

Apoptosis ▪ Apoptosis: programmed cell death – Enables organisms with millions of cells to maintain the right amount of cells ▪ Ced-3: a gene discovered by Robert Horvits and Michael Hengartner that assists in apoptosis – C. elegans with ced-3 mutations did not die when they normally would have

Does Apoptosis have to do with cancer? a)Yes b)No

A! ▪ Cancer: uncontrolled cell division ▪ Alterations in apoptosis can contribute heavily to cancer ▪ Even some human tissues are sculpted by apoptosis

Organism Development in Fruit Flies! ▪ Drosophila fruit flies were experimented on by Christiane Nüsslein- Volhard and Eric Wieschaus in the late 1970s ▪ Larvae express genes that set up orientation and segmentation – Establish bilateral symmetry through dorsal/ventral, anterior/posterior orientation ▪ During metamorphosis, genes are expressed to produce appendages in the thorax and head ▪ Gap Genes: Genes that are involved in the development of segmented embryos – Mutations occur such that an organism will lack an entire segment

Homeotic Genes ▪ In the 1950s, Edward Lewis discovered how the drosophila body plan is determined ▪ Homeotic Genes: Genes that control the development of an animal’s body plan ▪ In the Drosophila organism, the homeotic genes control specialization of body parts within the segments ▪ Homeosis: The process in which one body part becomes like another by assuming its identity – If a fly lacks a segment where a pair of legs are located (due to gap genes), its antennae are converted into an extra set

Homeotic genes in fruit flies But wait there’s more! ▪ Found in two clusters – Bithorax cluster – Antennapedia cluster ▪ These genes control the specialization of the segments they code for depending upon the mutations o the organism

Homeotic genes in vertebrates! Hox genes: Arranged in clusters Like the homeotic genes in Drosophila, hox genes are located in a 180-nucleotide region called the homeobox This section of DNA is responsible for regulation of gene transcription

Have a great day!