Genomes and Their Evolution Chapter 21

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

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

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

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

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 50,000-100,000 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

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

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

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

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

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

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

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