Genomes and their Evolution

Comparisons of genomes among organisms provide information about the evolutionary history of genes and taxonomic groups What genomic information distinguishes a human from a chimpanzee?

New approaches have accelerated the pace of genome sequencing

Cut the DNA into overlapping fragments short enough for sequencing Clone the fragments in plasmid or phage vectors. Sequence each fragment. Order the sequences into one overall sequence with computer software. Whole-Genome Shotgun Approach to Genome Sequencing- developed by Craig Venter

Scientists use bioinformatics to analyze genomes and their functions

Bioinformatics resources are provided by a number of sources

Comparison of sequences of “new” genes with those of known genes in other species may help identify new genes

Most recent common ancestor of all living things Billions of years ago Bacteria Eukarya Archaea Chimpanzee Human Mouse Millions of years ago Genome comparisons of closely related species help us understand recent evolutionary events

Translation and ribosomal functions Nuclear- cytoplasmic transport RNA processing Transcription and chromatin- related functions Mitochondrial functions Nuclear migration and protein degradation Mitosis DNA replication and repair Cell polarity and morphogenesis Protein folding, glycosylation, and cell wall biosynthesis Secretion and vesicle transport Metabolism and amino acid biosynthesis Peroxisomal functions Glutamate biosynthesis Serine- related biosynthesis Amino acid permease pathway Vesicle fusion Understanding Genes and Gene Expression at the Systems Level Danny Hillis Ted Talk Start at 8 minutes

By summer of 2007, the sequencing of more than 600 genomes had been completed.

Fig Exons (regions of genes coding for protein or giving rise to rRNA or tRNA) (1.5%) Repetitive DNA that includes transposable elements and related sequences (44%) Introns and regulatory sequences (24%) Unique noncoding DNA (15%) Repetitive DNA unrelated to transposable elements (15%) L1 sequences (17%) Alu elements (10%) Simple sequence DNA (3%) Large-segment duplications (5–6%) Eukaryotic genomes are larger and have more protein-coding genes. Eukaryotic genomes have more regulatory sequences. Greater complexity requires more regulation. Much of eukaryotic DNA is noncoding, including introns, gene control sequences, and repeated sequences.

Transposable Elements The first evidence for wandering DNA segments – Came from geneticist Barbara McClintock’s breeding experiments with Indian corn Nobel Prize 1983

Transposon New copy of transposon Insertion Transposon is copied Mobile transposon DNA of genome (a) Transposon movement (“copy-and-paste” mechanism) Retrotransposon New copy of retrotransposon Insertion Reverse transcriptase RNA (b) Retrotransposon movement Transposons, move by means of a DNA intermediate Retrotransposons move by means of an RNA intermediate

The transposable element can alter the expression of a gene at the new location

How Transposable Elements Contribute to Genome Evolution Movement of transposable elements – Occasionally generates new sequence combinations that are beneficial to the organism Some mechanisms – Can alter the functions of genes or their patterns of expression and regulation

Alu inserts as markers of primate evolution (retrotransposon) Salem, et al PNAS 100:

Genes and Multigene Families Many eukaryotic genes are present in one copy per haploid set of chromosomes The rest of the genome occurs in multigene families, collections of identical or very similar genes Some multigene families consist of identical DNA sequences, usually clustered tandemly, such as those that code for RNA products.

Fig a (a) Part of the ribosomal RNA gene family 18S 28S 18S5.8S rRNA DNA RNA transcripts Nontranscribed spacer Transcription unit

Heme Hemoglobin  -Globin  -Globin  -Globin gene family  -Globin gene family Chromosome 16 Chromosome 11 22 11   22 11   GG AA    Embryo Fetus and adult Adult α-globins and β-globins are examples of multigene families of nonidentical genes

Figure Duplication of ancestral gene Mutation in both copies Transposition to different chromosomes Further duplications and mutations Ancestral globin gene  -Globin gene family on chromosome 16  -Globin gene family on chromosome 11 Evolutionary time             2  1 22 11   GG AA   ICE FISH GENE DUPLICATION EVOLUTIONARY HISTORY CLIP

Alterations of Chromosome Structure Human chromosome 2 Telomere sequences Centromere sequences Chimpanzee chromosomes 12 Telomere-like sequences Centromere-like sequences Human chromosome (a) Human and chimpanzee chromosomes(b) Human and mouse chromosomes Mouse chromosomes Humans have 23 pairs of chromosomes, while chimpanzees have 24 pairs Chromosomal rearrangements are thought to contribute to the generation of new species

Most recent common ancestor of all living things Billions of years ago Bacteria Eukarya Archaea Chimpanzee Human Mouse Millions of years ago The accumulation of changes in the genome provides a record of evolutionary history

Comparing Genomes Within a Species As a species, humans have only been around about 200,000 years and have low within- species genetic variation Variation within humans is due to single nucleotide polymorphisms, inversions, deletions, and duplications These variations are useful for studying human evolution and human health

Other Repetitive DNA, Including Simple Sequence DNA Simple sequence DNA contains many copies of tandemly repeated short sequences This repeat number can vary from person to person, producing variation useful in forensic science.

STRBase: a short tandem repeat DNA database for the human identity testing community Christian M. Ruitberg, Dennis J. Reeder and John M. Butler* Biotechnology Division, National Institute of Standards and Technology, 100 Bureau Drive, Mail Stop 8311, Gaithersburg, MD , USA Abstract The National Institute of Standards and Technology (NIST) has compiled and maintained a Short Tandem Repeat DNA Internet Database ( since 1997 commonly referred to as STRBase. This database is an information resource for the forensic DNA typing community with details on commonly used short tandem repeat (STR) DNA markers. From: Nucl. Acids Res. (2001) 29 (1):

Comparing Developmental Processes Evolutionary developmental biology, or evo-devo, is the study of the evolution of developmental processes in multicellular organisms Genomic information shows that minor differences in gene sequence or regulation can result in major differences in form

Adult fruit fly Fruit fly embryo (10 hours) Fly chromosome Mouse chromosomes Mouse embryo (12 days) Adult mouse Molecular analysis of the homeotic genes in Drosophila has shown that they all include a sequence called a homeobox Hox genes Neil Shubin and Sean Carroll Discuss homeobox genes

GHOSTS

Fig Cut the DNA into overlapping fragments short enough for sequencing 1 2 Clone the fragments in plasmid or phage vectors. Whole-Genome Shotgun Approach to Genome Sequencing- developed by Craig Venter

Fig Cut the DNA into overlapping fragments short enough for sequencing Clone the fragments in plasmid or phage vectors. Sequence each fragment.

Fig Cytogenetic map Genes located by FISH Chromosome bands Three-Stage Approach to Genome Sequencing

Fig Cytogenetic map Genes located by FISH Chromosome bands Linkage mapping 1 Genetic markers

Fig Cytogenetic map Genes located by FISH Chromosome bands Linkage mapping 1 2 Genetic markers Physical mapping Overlapping fragments

Fig Cytogenetic map Genes located by FISH Chromosome bands Linkage mapping Genetic markers Physical mapping Overlapping fragments DNA sequencing

From: National Academy of Science, 2009 Metagenomics Genetic diversity is explored without isolating intact organisms.