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Regulation of Gene Expression Regulation of Gene Expression by Eukaryotes-typical human cell: only 20% of genes expressed at any given time-different cell types (with identical genomes) turn on different genes to cary out specific functions-differences between cell types is due to differential gene expression Eukaryotic gene expression regulated at different stages-Chromatin structure – tightly bound DNA less accessible for transcription-DNA methylation – methyl groups added to DNA; tightly packed; decreased transcription-histone acetylation – acetyl groups added to histones; loosened; increases transcription--histone tails protrude outward from a nucleosome – acetylation of tails promotes loose chromatin structure that permits transcription 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)-explains differences in identical twins Transcription initiation:-control elements bind transcription factors-enhances gene expression-Transcription Initiation Complex: enhancer regions bound to promoter region by activators Regulation of mRNA:-micro RNAs (miRNAs) and small interfering RNAs (siRNAs) can bind to mRNA and degrade it or block translation SUMMARY OF EUKARYOTIC GENE EXPRESSIONChromatin Modification:-genes in highly compacted chromatin are generally not transcribed-histone acetylation seems to loosen chromatin structure, enhancing transcription-DNA methylation generally reduces transcription-small or large noncoding RNAs can promote the formation of heterochromatin in certain regions, blocking transcription Transcription:-regulation of transcription initiation – DNA control elements in enhancers bind specific transcription factors. Bending of DNA enables activators to contact proteins at the promoter, initiating transcription.-coordinate regulation RNA Processing:-alternative RNA splicing mRNA Degradation:-each mRNA has a characteristic lifespan determined in part by sequences in the 5’ and 3’ UTRs-miRNA or siRNA can target specific mRNAs for destruction Translation:-initiation of translation can be controlled via regulation of initiation factors-miRNA or siRNA can block the translation of specific mRNAs Protein processing and degradation:-protein processing and degradation by proteasomes are subject to regulation Genomes and Their Evolution Human Genome Project-Purpose: to sequence the entire human genome-completed in 2003->1,200 genomes sequenced now (1000 bacteria, 80 archea, 124 eukaryotic species)-done via linkage mapping with genetic markers, physical mapping with overlapping fragments, and DNA sequencing Human DNA-3 billion base pairs- approx.. 20,000 genes-exons: only 1.5% codes for proteins (or RNA)-repetitive DNA: sequences present in multiple copies-transposable elements: -make up 75% of repetitive DNA -can be moved from one location to another in genome -discovered by Barbara McClintock – corn breeding experiments -2 kinds: transposons and retrotransposons--transposons: moves within genome via DNA intermediate. ‘Cut and paste’ or ‘copy and paste’ mechanisms. Requires enzyme transposase--retrotransposons: moves by means of RNA intermediate. Leaves copy at original site. Involves enzyme reverse transcriptase. Genome Evolution-duplication à genes with related function-genes diverge by accumulating mutations-some become nonfunctional pseudogenes-eventually new genes with new functions can occur Multigene families-collections of 2 or more identical or very similar genes-ex: hemoglobin: alpha-globin and beta-globin gene families-ex: antifreeze gene in fish-antifreeze proteins (AFP): produced by vertebrates, plants, fungi, bacteria to aid survival in sub-zero environments -function: bind to ice crystals and prevent growth-antarctic fish: old protein gene transformed into a new gene with new structure/function -gene mutates à duplicated à divergent-transpositions à chromosomal rearrangements Transposable Elements Contribute to Evolution-promote recombination, disrupt genes or control elements, and carry genes to new locations-may be harmful or lethal, but can also have small beneficial effects-provides raw material for natural selection Evolutionary Development (Evo-devo)-compares developmental processes to understand how changes can lead to evolution of organisms-homeotic genes = master regulatory genes – control placement and spatial organization of body parts-homeobox: widely conserved 180-nucleotide sequence within homeotic (Hox) gene sequence -found in many groups (fungi, animals, plants) -hints at relatedness between all life forms
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