Genomes and their evolution

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Presentation transcript:

Genomes and their evolution Chapter 21

You must know How prokaryotic genomes compare to eukaryotic genomes. Applications of bioinformatics to medicine, evolution, and health. The activity and role of transposable elements and retrotransposons in generating genetic diversity. How evo-devo relates to our understanding of the evolution of genomes. The role of homeotic genes and homeoboxes in developmental patterns and sequences.

3-stage Approach to genome sequencing: Human genome project Linkage map- ordering of genetic markers, showing the relative distance between them. The markers can be genes or other identifiable sequences in the DNA. Like RFLP’s or short tandem repeats (STRs): We will talk more about these next class. Physical mapping- A genetic map in which the actual physical distances between genes or other genetic markers are expressed, usually as the number of base pairs along the DNA. DNA sequencing- Determination of nucleotide sequence of each fragment and assembly of the partial sequences into the complete genome sequence. The ultimate goal in mapping is to determine the complete nucleotide sequence of each chromosome.

Whole-genome Shotgun approach Essentially skips the linkage mapping and physical mapping stages and starts directly with the sequencing of DNA fragments from randomly cut DNA. These technology advances have facilitated an approach called metagenomics, which DNA from a group of species is collected and sequenced. This eliminates culturing each species separately.

Scientists use bioinformatics to analyze genomes and their functions Bioinformatics is the use of computers, software, and mathematical models to process and integrate the incredible volume of data from sequencing projects such as the Human Genome Project. Using DNA sequences scientists can study genes directly, without having to infer genotype from phenotype. This approach (reverse genetics) poses a new challenge: determining the phenotype from the genotype. Scientist aim to identify all proteins-coding genes in the sequence and ultimately their functions, this is called gene annotation. Which can now be done by computers. In addition to DNA sequences, protein interactions are analyzed in an approach called proteomics.

Medical applications Understanding and treatment of cancer. The Cancer Genome Atlas: set out to find the three most common types of cancer (lung, ovarian and glioblastoma of the brain). By comparing gene sequences and patterns of gene expression in cancer cells with those of normal cells, specific treatments can be administered. Personalized medication, disease prevention and treatment. The more we can learn about the arrangement and interactions of the components of the genetic systems, the deeper our understanding will be.

Genomes vary is size, number of genes and gene density More than 3,700 genomes have been sequenced with thousands more in progress. In general, bacteria and archaea have fewer genes than eukaryotes, and the number of genes in eukaryotic genomes is less than was expected. There does not seem to be any correlation between the complexity of an organism and its number of genes. The 1mm nematode C. elegans and humans both have between 20,000 and 21,000 genes. The human genome is able to function with relatively few genes by utilizing alternative splicing of RNA transcripts. *Recall: This process results in more than one functional protein from a single gene. Density: (amount of genes in a given length of DNA) Gene density is relatively low in humans.

Noncoding DNA Only about 1.5% of the human genome codes for proteins or is transcribed into rRNAs or tRNAs. The rest, located between functional genes, includes some unique noncoding DNA, such as gene fragments and pseudogenes, former genes that have accumulated mutations over a long time and no longer produce functional proteins. Much of the rest is repetitive DNA, sequences that are present in multiple copies in the genome.

Transposable Elements Both prokaryotes and eukaryotes have stretches of DNA that can move from one location to another within the genome. These are known as transposable elements. During a process called, transposition, a transposable element moves from one site in a cells DNA to a different target sit by a type of recombination process. These stretches of DNA move from one location to another in the genome with the aid of an enzyme, transposase. Transposase can interrupt normal gene function if inserted in the middle of a functional gene, or alter gene expression if inserted into a regualatory element. Although these effects may be harmful or lethal, over many generations some may have small beneficial effects.

Multigene families Are collections of two or more identical or very similar genes. Ex. Human alpha-globlin and beta-globin gene families. The genes are on different chromosomes. This allows for different forms of the beta- globin gene to function at different times in the human life cycle. For example, the embryonic and fetal forms of hemoglobin have a higher affinity for oxygen than the adult forms, ensuring the efficient transfer of oxygen from mother to fetus. This variety allows hemoglobin to function effectively in the changing environment of the developing animal.

Genome evolution Duplication: An accident in meiosis resulting in one or more extra sets of chromosomes, polyploidy. One set of genes can provide essential functions for the organism. This set can diverge by accumulating mutations, which may persist if the organism survives and reproduces. Ex. Hemo-globin This can result in speciation, the development of a new species. Rearrangement: exon duplication and shuffling. Mutations

Comparing genome sequence provides clue to evolution Determining which genes have remained similar, are highly conserved, in distantly related species can help clarify evolutionary relationships among species that diverged from each other long ago. Evo-devo: is a field of biology that compares developmental processes to understand how they may have evolved and how changes can modify existing organismal features or lead to new ones. Homeotic genes are master regulatory genes that control placement and spatial organization of body parts by controlling the developmental fate of groups of cells. A homeobox is a widely conserved 180-nucleotide sequence found within homeotic genes. *highly conserved mean that it is found in many groups ( fungi, animals, and plants). This hints at the relatedness and common evolution of all life-forms.