1. Genomes and Their Evolution
Chapter 21

2. Bioinformatics
Scientists have used the advances of genetics and computers to further understanding
GenBank
BLAST
Protein Data Bank
National Library of Medicine and National Institute for Health created National Library for Biotechnology Information
GenBank – NCBI database of genetic sequences
*119 million fragments as of may 2010, 114 million base pairs
*constantly updated
BLAST – can compare a DNA sequence with every sequence in GenBank base by base
A third program can search any protein sequence and show its three d shape
Protein Data Bank is managed by Rutgers and University of California, San Diego

3. Bioinformatics No longer have to infer genotype from phenotype
Goal now is to identify all protein coding regions – gene annotation
Software looks for certain short sequences that specify known mRNA’s
Use of known proteins is used to predict new protein sequences

4. Bioinformatics Project ENCODE
Researchers focused on 1% of human genome
Looked for protein coding genes, noncoding RNA’s, and regulatory sequences
90% of the region was transcribed into RNA
BUT only 2% coded for proteins

5. Bioinformatics Cancer Genome Atlas
Project of the National Cancer Institute and NIH
Analyzed interacting genes and their role in cancer
Three types: Lung, ovarian, and glioblastoma
Glioblastoma research has shown the most promise
Looked at common mutations in the tree types of cancers
Glioblastoma has shown the role of several suspected genes and identified a few unknown genes which may provide targets for therapy

6. Genomes Genomes vary in size, density, and number of genes
Size – Both bacteria are similar in size and much smaller than eukaryotes
Density – Eukayotes have a smaller gene density that bacteria
Genes – same as size
Size – bacteria roughly 4 Mb (million base pairs) compared to humans with 3,000 Mb
Density – bacteria use most of their genomes for coding regions therefore much more dense while most eukaryotes have noncoding regions that decrease the density
Genes – as expected eukaryotes have more genes that bacteria
Interesting – during Human Genome Project researchers expected to find between 50, ,000 genes but in actuallity there are fewer than 21,000 – why?
Due to alternative RNA splicing which gives more than one protein for a gene
One day people may carry their entire genome on a chip which can be analyzed by physicians and researchers for individualized treatment

7. Noncoding DNA Previously called “junk DNA”
Only 1.5% of the human genome codes for proteins or RNA’s
Gene regulatory sequences (5%) and introns (20%)
Pseudogenes
Regions that have accumulated mutations over time

8. Transposable Elements
Made up of repetitive DNA
Account for 25-50% of the genome
Elements move from one spot in the DNA to another – transposition
Can occur through the DNA bending
Eukaryotic types:
Transposons
Retrotransposons
Transposons – move via a DNA intermediate, either by cut and past (removes the element) or copy and paste (leaves a copy)
*uses transposase
Retrotransposons – move via an RNA intermediate
Always leaves a copy of the original site during transposition
*Uses reverse transcriptase like a retrovirus
Alu elements – transposable elements in humans that make up ~10% of the genome
-About 300 nucleotides long
-Do not code for any protein
-Do code for RNA
-Function unknown
L1- (Line 1) element
-Much longer than Alu
-6,500 base pairs
-Low rate of transposition
-Recent research shows they block RNA polymerase which is necessary for transposition
-May regulate gene expression

9. Alteration of DNA
Meiosis errors can result in extra chromosomes – polyploidy
If the organism survives one set of chromosomes can mutate and form new, novel genes
Typically polyploidy events are lethal but if they survive and one set of chromosomes can drive function, the other can mutate and give rise to new genes

10. Alteration of DNA Humans and chimps diverged about 6 million years ago
Humans 23 chromosomes
Chimps 24 chromosomes
Chimp chromosomes formed to make a human chromosome
Banding pattern of chimp chromosome 12 and 13 matches bands on human chromosome 2
Chromosome 16 matches chromosomes 7, 8, 16, and 17 – shoes the evolution of the mouse and human together

11. Alteration of DNA
Crossing over or replication errors can lead one chromosome with a deletion and one with a duplication
Over time this can lead to STR’s or repeating units
Can be used for analysis

12. Transposable elements and Evolution
These elements can play an important role evolution
Promote recombination
Disrupt cellular genes or control elements
Carry genes/exons to new locations

13. Comparing Genomes
Comparing conserved genes in distantly related species can clarify evolutionary relationships – show lines of divergence
Comparing closely related species serves many functions:
Sequences can be used as a scaffold for another species
Comparing different species allows for determination what makes a species
FOXP2 – involved in the vocalization in vertebrates
Evolving faster in humans than mice
Humans and chimps only differ by 1.2% comparing single nucleotides
Researchers when looking at phenotype have found a number of genes evolving faster in humans than in chimps or mice
FOXP2 is found in brains of zebra finch and canaries when they are learning their songs
Researchers further demonstrated the effects of FOXP2 in mice – knocked out the gene - mice didn’t develop brains fully and didn’t produce normal ultrasonic vocalizations
Placed a humanized copy of FOXP2 in mice – mice showed fully developed brains but also showed different vocalization patterns