Eukaryotic Genomes  The Organization and Control of Eukaryotic Genomes

Gene Expression  In multicellular organisms, the first place gene expression is controlled is through cell differentiation  After the zygote forms and cells are forming through mitosis, cells are “programmed” to become specific cell types  Depending on the cell type, certain “sets” of genes will be expressed

Gene expression  Since each cell has all the DNA of the organisms’ genome, the cell type is not controlled by the presence of “certain” genes  Instead, only certain genes are “active” (only about 17% of a cells genes)  This process of differential gene expression determines cell type and function  NOTE: Only about 3% of the DNA in your genome actually codes for proteins

 Overview of the different ways that eukaryotic genes can be expressed in cells

Chromatin Structure:  Tightly bound DNA less accessible for transcription  DNA methylation : methyl groups added to DNA; tightly packed;  transcription  Histone acetylation : acetyl groups added to histones; loosened;  transcription

Acetylation of histone  The protein side chains of the histone molecule normally have charges associated with them  REMINDER: Protein structure – the side chains allow the amino acids to bind to each other and create a tertiary protein structure  When you acetylate the histone tails, you BLOCK these charges and allow the chromatin to unravel.

DNA Methylation  DNA methylation also seems to be responsible for inactivating certain genes (blocks them from transcription)  Again, this aids in cell differentiation  Methylation is what is responsible for genomic imprinting  From previous unit (where gene expression is determined by the parent the allele was inherited from)

Epigenetic Inheritance  Modifications on chromatin can be passed on to future generations  Unlike DNA mutations, these changes to chromatin can be reversed (de- methylation of DNA)  This can affect the expression of different genes (do you have transcriptional access?)  Explains differences between identical twins

Transcription Initiation:  Control elements: segments of noncoding DNA that can bind transcription factors (proteins that aid RNA polymerase in transcription)  Enhances gene expression

Activator vs. Repressor  There are distant control elements (enhancers) on the DNA strand that can affect transcription  Activators is a protein complex that binds to the enhancer help initiate transcription  Repressors are protein complexes that inhibit transcription

Enhancer promoter activators Enhancer regions bound to promoter region by activators

Regulation of mRNA: One way to regulate mRNA is by alternate splicing This allows the splicing of different exons and introns to alter protein expression micro RNAs (miRNAs) small interfering RNAs (siRNAs) micro RNAs (miRNAs) and small interfering RNAs (siRNAs) can bind to mRNA and degrade it or block translation

RNA inhibition microRNAs (miRNAs)  Single stranded RNA molecules that bind to mRNA  These allow the mRNA strand to be degraded or blocks translation Small interfering RNAs (siRNAs)  Similar to miRNAs  Since these usually destroy the mRNA strand, it is believed to have developed to fight viruses

Translation Controls  Regulatory proteins can alter translation:  Certain mRNA sequences can be blocked and prevent attachment to the ribosome  Enzymes can add to the poly-A tail of mRNA to aid translation of the mRNA  Global regulation:  Either activate or inactivate protein factors that affect the initiation of translation

Protein modification  Regulatory proteins can affect the modification of proteins created after translation:  Can affect phosphorylation (alter shape)  Alter protein markers to alter the destination of protein  Regulate the life-span of proteins  Label proteins with a molecule called ubiquitin  Proteins called proteasomes recognize the ubiquitin and degrade the protein

Genomic DNA and evolution

Mutation  The basis for change at the level of DNA is mutation  Earliest life probably had a limited number of genes (simple organisms)  Mutations allowed for genetic sequences not only to change, but to grow and incorporate additional genetic information into the genome

Chromosome duplication  Because of an accident in meiosis (nondisjunction), the number of chromosomes can be altered in a cell (remember trisomy)  These extra sets of genes can persist and acquire mutations (eventually new species)  Therefore, it is possible to acquire new “traits” that can be passed on to offspring  If the trait is lethal, the individuals that have the gene are carriers  Possible method that genetic diseases arose

Crossing over  Crossing over allows for a tremendous amount of variability  Errors in crossing over can cause deletions or duplications of genetic material  If you have duplication errors, you can create a lot of genes with similar functions (create similar proteins)  EXAMPLE: Similarities in the globin proteins (a family of proteins with varied functions)

Transposable elements  Sometimes there are segments of DNA that can “cross-over” when the chromosomes are not aligned or cross- over to non-sister chromatids  These “jumping genes” introduce even more chances for mutation  There are still quite a few transposable elements remaining in the eukaryotic genome... possible future mutations

Exon duplication/shuffling  Not all DNA codes for proteins (introns vs. exons)  Some exons could be duplicated or deleted from chromosomes  Gives the freedom to rearrange exon sequence and alter amino acid sequence  This shuffling of amino acids can create variations of the protein with similar (but new) functions