Chapter 20: The Evolution of Genomes PDF

Chapter 20 The Evolution of Genomes Lecture Presentations by Nicole Tunbridge and © 2021 Pearson Education Ltd....

Chapter 20 The Evolution of Genomes Lecture Presentations by Nicole Tunbridge and © 2021 Pearson Education Ltd. Kathleen Fitzpatrick Figure 20.1b © 2021 Pearson Education Ltd. Identifying Protein-Coding Genes and Understanding Their Functions Using available DNA sequences, geneticists can study genes directly The identification of protein-coding genes within DNA sequences in a database is called gene annotation © 2021 Pearson Education Ltd.  Gene annotation uses three lines of evidence to identify a gene First computers search for patterns that indicate the presence of genes – This includes translational start and stop signals, RNA splicing sites, and other signs, such as promoter sequences – The software also looks for short sequences that specify known mRNAs © 2021 Pearson Education Ltd.  The second step is to obtain clues about the identities and functions – Software is used to compare the sequence of a protein to the products of known genes from other organisms The final step is to use RNA-seq or some other method to show that the relevant RNA is actually expressed from the proposed gene © 2021 Pearson Education Ltd. Understanding Genes and Gene Expression at the Systems Level Genomics is a rich source of new insights into questions about genome organization, regulation of gene expression, embryonic development, and evolution The ENCODE (Encyclopedia of DNA Elements) project ran from 2003 to 2012 The aim was to learn about the functionally important elements in the human genome © 2021 Pearson Education Ltd.  Besides working to identify enhancers and promoters, investigators also extensively characterized histone and DNA modifications and chromatin structure This project allows comparison of results from different projects, yielding a richer picture of the whole genome © 2021 Pearson Education Ltd.  About 75% of the genome is transcribed at some point in at least one cell type studied Biochemical functions have been assigned to DNA elements making up at least 80% of the genome The ENCODE project analyzed cells in culture, so its potential for clinical applications was limited © 2021 Pearson Education Ltd.  A related project called the Roadmap Epigenomics Project set out to characterize the epigenetic features of the genome (the epigenome) A useful finding was that the original tissue in which a cancer arose can be identified in a secondary tumor based on its epigenomic features © 2021 Pearson Education Ltd. Systems Biology Proteomics is an approach to studying large sets of proteins and their properties A proteome is the entire set of proteins expressed by a cell or group of cells Biologists have begun to compile catalogs of genes and proteins and have begun to focus on their functional integration in biological systems This approach is called systems biology © 2021 Pearson Education Ltd.  Researchers working on the yeast Saccharomyces cerevisiae used sophisticated techniques to disable pairs of genes one pair at a time, creating double mutants Computer software then mapped genes to produce a network-like “functional map” of their interactions The systems biology approach is possible because of advances in bioinformatics © 2021 Pearson Education Ltd. Figure 20.4 © 2021 Pearson Education Ltd. Application of Systems Biology to Medicine The Cancer Genome Atlas project culminated in 2018 with publications called the Pan-Cancer Atlas In this project, many interacting genes and gene products were analyzed together as a group High-throughput techniques are increasingly being applied to the problem of cancer Overall, the Pan-Cancer Atlas contributed significantly to understanding how, where, and why tumors arise © 2021 Pearson Education Ltd.  DNA microarrays on glass or silicon chips and, increasingly, RNA-seq are used to analyze gene expression patterns in patients with cancers or other diseases Analyzing which genes are overexpressed or underexpressed in a cancer allows physicians to tailor the treatment to unique genetic makeup of the patient and the cancer © 2021 Pearson Education Ltd. Figure 20.5 © 2021 Pearson Education Ltd. CONCEPT 20.3: Genomes vary in size, number of genes, and gene density The sequences of thousands of genomes have been completed Tens of thousands of genomes are either in progress or are considered permanent drafts Among the sequences in progress are roughly 22,000 metagenomes © 2021 Pearson Education Ltd. Genome Size Genomes of most bacteria and archaea range from 1 to 6 million base pairs (Mb) Eukaryotic genomes tend to be larger Most plants and animals have genomes greater than 100 Mb; humans have 3,000 Mb Within each domain, there is no systematic relationship between genome size and phenotype © 2021 Pearson Education Ltd. Table 20.1 © 2021 Pearson Education Ltd. Number of Genes Free-living bacteria and archaea have 1,500 to 7,500 genes Unicellular fungi have about 5,000 genes and multicellular eukaryotes up to at least 40,000 genes Number of genes is not correlated to genome size © 2021 Pearson Education Ltd.  It is estimated that the nematode C. elegans has 100 Mb and 20,100 genes, while Drosophila melanogaster has 165 Mb and 14,000 genes Researchers predicted the human genome would contain about 50,000 to 100,000 genes; however, the number is around 21,300 Vertebrate genomes can produce more than one polypeptide per gene because of alternative splicing of RNA transcripts © 2021 Pearson Education Ltd. Gene Density and Noncoding DNA Humans and other mammals have the lowest gene density, or number of genes in a given length of DNA Multicellular eukaryotes have many introns within genes and a large amount of noncoding DNA between genes © 2021 Pearson Education Ltd. CONCEPT 20.4: Multicellular eukaryotes have a lot of noncoding DNA and many multigene families Sequencing of the human genome revealed that 98.5% does not code for proteins, rRNAs, or tRNAs Gene regulatory sequences and introns account for 5% and 20%, respectively, of the human genome © 2021 Pearson Education Ltd.  Noncoding DNA, found between genes, includes: – Pseudogenes, former genes that have accumulated mutations and are nonfunctional – Repetitive DNA, present in multiple copies in the genome A high level of sequence conservation in some noncoding DNA among humans, rats, and mice suggests that these regions have important functions © 2021 Pearson Education Ltd. Figure 20.6 © 2021 Pearson Education Ltd. Transposable Elements and Related Sequences Prokaryotes and eukaryotes have stretches of DNA that can move from one location to another within the genome, called transposable elements About 75% of human repetitive DNA is made up of transposable elements and the sequences related to them The first evidence of these mobile elements came from Barbara McClintock’s breeding experiments with Indian corn (maize) © 2021 Pearson Education Ltd. Figure 20.7 © 2021 Pearson Education Ltd. Sequences Related to Transposable Elements Multiple copies of transposable elements and related sequences are scattered throughout eukaryotic genomes In humans and other primates, a large portion of transposable element–related DNA consists of a family of similar sequences called Alu elements Many Alu elements are transcribed into RNA molecules; some are thought to help regulate gene expression © 2021 Pearson Education Ltd. Genes and Multigene Families Many eukaryotic genes are present in one copy per haploid set of chromosomes The rest of the genes occur in multigene families, collections of two or more identical or very similar genes Some multigene families consist of identical DNA sequences, usually clustered tandemly, such as those that code for rRNA products © 2021 Pearson Education Ltd. Figure 20.10 © 2021 Pearson Education Ltd.  The classic examples of multigene families of nonidentical genes are two related families of genes that encode globins α-globins and β-globins are polypeptides of hemoglobin coded by genes on different human chromosomes and are expressed at different times in development © 2021 Pearson Education Ltd. CONCEPT 20.5: Duplication, rearrangement, and mutation of DNA contribute to genome evolution The basis of change at the genomic level is mutation, which underlies much of genome evolution The earliest forms of life likely had only those genes necessary for survival and reproduction The size of genomes has increased over evolutionary time, with the extra genetic material providing raw material for gene diversification © 2021 Pearson Education Ltd. Duplication of Entire Chromosome Sets Accidents in meiosis can lead to one or more extra sets of chromosomes, a condition known as polyploidy The genes in one or more of the extra sets can diverge by accumulating mutations These variations may persist if the organism carrying them survives and reproduces In this way, genes with novel functions can evolve © 2021 Pearson Education Ltd. Alterations of Chromosome Structure Humans have 23 pairs of chromosomes, while chimpanzees have 24 pairs Following the divergence of humans and chimpanzees from a common ancestor, two ancestral chromosomes fused in the human line Large blocks of genes on human chromosome 16 are found on four mouse chromosomes This indicates that the genes in each block stayed together in both the human and mouse lineages © 2021 Pearson Education Ltd. Figure 20.11 © 2021 Pearson Education Ltd. Figure 20.12 © 2021 Pearson Education Ltd.  Comparative analysis between chromosomes of humans and six other mammalian species paints a hypothetical chromosomal evolutionary history The rate of duplications and inversions seems to have accelerated about 100 million years ago This coincides with when large dinosaurs went extinct and mammals diversified Chromosomal rearrangements are thought to contribute to the generation of new species © 2021 Pearson Education Ltd. Evolution of Genes with Novel Functions One copy of a duplicated gene can undergo alterations that lead to a completely new function for the protein product For example, the lysozyme gene was duplicated and evolved into the gene that encodes α-lactalbumin in mammals Lysozyme is an enzyme that helps protect animals against bacterial infection α-lactalbumin is a nonenzymatic protein that plays a role in milk production in mammals © 2021 Pearson Education Ltd. Figure 20.15 © 2021 Pearson Education Ltd. Rearrangements of Parts of Genes: Exon Duplication and Exon Shuffling Errors in meiosis can result in an exon being duplicated on one chromosome and deleted from the homologous chromosome In exon shuffling, errors in meiotic recombination lead to some mixing and matching of exons, either within a gene or between two nonallelic genes The current version of the gene for tissue plasminogen activator (TPA) is thought to have arisen by several instances of exon shuffling and subsequent duplication © 2021 Pearson Education Ltd. Figure 20.16 © 2021 Pearson Education Ltd. How Transposable Elements Contribute to Genome Evolution Multiple copies of similar transposable elements facilitate recombination, or crossing over, between different chromosomes Insertion of transposable elements within a protein- coding sequence may block protein production Insertion of transposable elements within a regulatory sequence may increase or decrease protein production © 2021 Pearson Education Ltd.  Transposable elements may carry a gene or groups of genes to a new position Transposable elements may also create new sites for alternative splicing in an RNA transcript In all cases, changes are usually detrimental but may on occasion prove advantageous to an organism © 2021 Pearson Education Ltd.