Chapter 8 Genome Evolution

8.2 DNA Sequences Evolve by Mutation and a Sorting Mechanism The probability of a mutation is influenced by the likelihood that the particular error will occur and the likelihood that it will be repaired. synonymous mutation – A change in DNA sequence in a coding region that does not alter the amino acid sequence of the polypeptide product. nonsynonymous mutation –A change in DNA sequence in a coding region that alters the amino acid sequence of the polypeptide product.  

8.2 DNA Sequences Evolve by Mutation and a Sorting Mechanism In small populations, the frequency of a mutation will change randomly and new mutations are likely to be eliminated by chance. fixation –The process by which a new allele replaces the allele that was previously predominant in a population.

8.2 DNA Sequences Evolve by Mutation and a Sorting Mechanism The frequency of a neutral mutation largely depends on genetic drift, the strength of which depends on the size of the population. The frequency of a mutation that affects phenotype will be influenced by negative or positive selection. Data courtesy of Kent E. Holsinger, University of Connecticut [http://darwin.eeb.uconn.edu] Data courtesy of Kent E. Holsinger, University of Connecticut [http://darwin.eeb.uconn.edu] Figure 08.01: The fixation or loss of alleles by random genetic drift.

8.3 Selection Can Be Detected by Measuring Sequence Variation The ratio of nonsynonymous to synonymous substitutions in the evolutionary history of a gene is a measure of positive or negative selection. Low heterozygosity of a gene may indicate recent selective events. genetic hitchhiking – The change in frequency of a genetic variant due to its linkage to a selected variant at another locus.

Figure 08.02: Nonsynonymous and synonymous variation in the Adh locus in Drosophila melanogaster (“polymorphic”) and between D. melanogaster, D. simulans, and D. yakuba (“fixed”). Adapted from J. H. McDonald, J. H. and M. Kreitman, Nature 351 (1991): 652-654.

8.3 Selection Can Be Detected by Measuring Sequence Variation Comparing the rates of substitution among related species can indicate whether selection on the gene has occurred. linkage disequilibrium – A nonrandom association between alleles at two different loci, often as a result of linkage. Figure 08.03: A higher number of nonsynonymous substitutions in lysozyme sequences in the cow/deer lineage as compared to the pig lineage. Adapted from N. H. Barton, et al. Evolution. Cold Spring Harbor Laboratory Press, 2007. Original figure appeared in J. H. Gillespie, The Causes of Molecular Evolution. Oxford University Press, 1991.

8.3 Selection Can Be Detected by Measuring Sequence Variation Reproduced from R. M. Clark, et al., Proc. Natl. Acad. Sci. USA 101 (2004): 700-707. Copyright © 2004 National Academy of Sciences, U.S.A. Courtesy of John F. Doebley, University of Wisconsin, Madison Figure 08.04: Nucleotide diversity (pi) of the tb1 region in domesticated maize is much lower than in wild teosinte, indicating strong selection on this locus in maize. Figure 08.05: The fraction of recombinants between an allele of G6PD and alleles at nearby loci on a human chromosome remains low. Adapted from E. T. Wang, et al., Proc. Natl. Acad. Sci. USA 103 (2006): 135-140.

8.4 A Constant Rate of Sequence Divergence Is a Molecular Clock The sequences of orthologous genes in different species vary at nonsynonymous sites (where mutations have caused amino acid substitutions) and synonymous sites (where mutation has not affected the amino acid sequence). Synonymous substitutions accumulate ~10× faster than nonsynonymous substitutions.

8.4 A Constant Rate of Sequence Divergence Is a Molecular Clock Reproduced with kind permission from Springer Science+Business Media: J. Mol. Evol., The structure of cytochrome and the rates of molecular evolution, vol. 1, 1971, pp. 26-45, R. E. Dickerson, fig. 3. Courtesy of Richard Dickerson, University of California, Los Angeles. Figure 08.06: The rate of evolution of three types of proteins over time. The approximately constant rate of evolution of each protein type is a molecular clock.

8.4 A Constant Rate of Sequence Divergence Is a Molecular Clock The evolutionary divergence between two DNA sequences is measured by the corrected percent of positions at which the corresponding nucleotides differ. Substitutions may accumulate at a more or less constant rate after genes separate, so that the divergence between any pair of globin sequences is proportional to the time since they shared common ancestry. Figure 08.07: Divergence of DNA sequences depends on evolutionary separation. Each point on the graph represents a pairwise comparison.

8.4 A Constant Rate of Sequence Divergence Is a Molecular Clock Figure 08.08: All globin genes have evolved by a series of duplications, transpositions, and mutations from a single ancestral gene. Figure 08.09: This tree accounts for the separation of classes of globin genes.

8.4 A Constant Rate of Sequence Divergence Is a Molecular Clock codon bias – A higher usage of one codon in genes to encode amino acids for which there are several synonymous codons.

8.5 The Rate of Neutral Substitution Can Be Measured from Divergence of Repeated Sequences The rate of substitution per year at neutral sites is greater in the mouse genome than in the human genome, probably because of a higher mutation rate. Figure 08.10: An ancestral consensus sequence for a family is calculated by taking the most common base at each position.

8.6 How Did Interrupted Genes Evolve? A major evolutionary question is whether genes originated with introns or whether they were originally uninterrupted. “introns late” model – The hypothesis that the earliest genes did not contain introns, and that introns were subsequently added to some genes.

8.6 How Did Interrupted Genes Evolve? Interrupted genes that correspond either to proteins or to independently functioning nonprotein-encoding RNAs probably originated in an interrupted form (the “introns early” hypothesis). exon shuffling – The hypothesis that genes have evolved by the recombination of various exons encoding functional protein domains. Figure 08.11: An exon surrounded by flanking sequences that is translocated into an intron may be spliced into the RNA product.

8.6 How Did Interrupted Genes Evolve? A special class of introns is mobile and can insert themselves into genes.

8.7 Why Are Some Genomes So Large? There is no clear correlation between genome size and genetic complexity. C-value – The total amount of DNA in the genome (per haploid set of chromosomes). C-value paradox – The lack of relationship between the DNA content (C-value) of an organism and its coding potential. Figure 08.12: DNA content of the haploid genome increases with morphological complexity of lower eukaryotes, but varies extensively within some groups of higher eukaryotes.

8.7 Why Are Some Genomes So Large? There is an increase in the minimum genome size associated with organisms of increasing complexity. There are wide variations in the genome sizes of organisms within many taxonomic groups. Figure 08.13: The minimum genome size found in each taxon increases from prokaryotes to mammals.

8.8 Morphological Complexity Evolves by Adding New Gene Functions In general, comparisons of eukaryotes to prokaryotes, multicellular to unicellular eukaryotes, and vertebrate animals to invertebrate animals show a positive correlation between gene number and morphological complexity as additional genes are needed with generally increased complexity. Figure 08.15: Human genes can be classified according to how widely their homologues are distributed in other species.

8.8 Morphological Complexity Evolves by Adding New Gene Functions Figure 08.16: Common eukaryotic proteins are concerned with essential cellular functions. Figure 08.17: Increasing complexity in eukaryotes is accompanied by accumulation of new proteins for transmembrane and extracellular functions.

8.9 Gene Duplication Contributes to Genome Evolution Most of the genes that are unique to vertebrates are concerned with the immune or nervous systems. Duplicated genes may diverge to generate different genes, or one copy may become an inactive pseudogene. Figure 08.18: After a globin gene has been duplicated, differences may accumulate between the copies. The genes may acquire different functions or one of the copies may become inactive.

8.10 Globin Clusters Arise by Duplication and Divergence All globin genes are descended by duplication and mutation from an ancestral gene that had three exons. The ancestral gene gave rise to myoglobin, leghemoglobin, and α and  globins. The α- and -globin genes separated in the period of early vertebrate evolution, after which duplications generated the individual clusters of separate α- and -like genes. Figure 08.19: Each of the alpha-like and beta-like globin gene families is organized into a single cluster that includes functional genes and pseudogenes (psi).

8.10 Globin Clusters Arise by Duplication and Divergence nonallelic genes – Two (or more) copies of the same gene that are present at different locations in the genome (contrasted with alleles, which are copies of the same gene derived from different parents and present at the same location on the homologous chromosomes). Once a gene has been inactivated by mutation, it may accumulate further mutations and become a pseudogene (), which is homologous to the active gene(s) but has no functional role.

8.10 Globin Clusters Arise by Duplication and Divergence Figure 08.20: Different hemoglobin genes are expressed during embryonic, fetal, and adult periods of human development. Figure 08.21: Clusters of -globin genes and pseudogenes are found in vertebrates.

8.11 Pseudogenes Are Nonfunctional Gene Copies Processed pseudogenes result from reverse transcription and integration of mRNA transcripts. Nonprocessed pseudogenes result from incomplete duplication or second-copy mutation of functional genes. Some pseudogenes may gain functions different from those of their parent genes, such as regulation of gene expression, and take on different names. Figure 08.22: Many changes have occurred in a -globin gene since it became a pseudogene.

8.12 Genome Duplication Has Played a Role in Plant and Vertebrate Evolution Genome duplication occurs when polyploidization increases the chromosome number by a multiple of two. autopolyploidy – Polyploidization resulting from mitotic or meiotic errors within a species. allopolyploidy – Polyploidization resulting from hybridization between two different but reproductively compatible species.

Figure 08.24: Genomnic Duplication 8.12 Genome Duplication Has Played a Role in Plant and Vertebrate Evolution Genome duplication events can be obscured by the evolution and/or loss of duplicates as well as by chromosome rearrangements. Genome duplication has been detected in the evolutionary history of many flowering plants and of vertebrate animals. 2R hypothesis – The hypothesis that the early vertebrate genome underwent two rounds of duplication. Figure 08.24: Genomnic Duplication Adapted from G. Blanc and K. H. Wolfe, Plant Cell 16 (2004): 1667-1678.

8.13 What Is The Role of Transposable Elements in Genome Evolution? Transposable elements tend to increase in copy number when introduced to a genome but are kept in check by negative selection and transposition regulation mechanisms.

8.14 There May Be Biases in Mutation, Gene Conversion, and Codon Usage Mutational bias may account for a high AT content in organismal genomes. Gene conversion bias, which tends to increase GC content, may act in partial opposition the mutational bias. Codon bias may be a result of adaptive mechanisms that favor particular sequences, and of gene conversion bias.