1. Chapter 21 Genes and their Evolution

2. Overview: Reading the Leaves from the Tree of Life Genome sequencing enabled scientists to sequence the human genome by 2003 and the genome of the chimp by 2005. Complete genome sequences exist for a human, chimpanzee, E. coli, brewer’s yeast, nematode, fruit fly, house mouse, rhesus macaque, and other organisms Fragments of DNA have been sequenced from extinct species, including the woolly mammoth. Comparing the genomes of more distantly related animals should reveal the sets of genes that control group-defining characteristics. Comparing the genomes of plants and prokaryotes provides information about the long evolutionary history of shared ancient genes and their products. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

3. Genomics & Bioinformatic With the genomes of many species fully sequenced, scientists can study whole sets of genes and their interactions, an approach called genomics. The sequencing efforts that contribute to this approach generate enormous volumes of data. The need to deal with this information has spawned the field of bioinformatics- the application of computational methods to the storage and analysis of biological data. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

4. New approaches have accelerated the pace of genome sequencing The most ambitious mapping project to date has been the sequencing of the human genome Officially begun as the Human Genome Project in 1990, the sequencing was completed by 2003 The project had three stages: 1. Genetic (or linkage) mapping 2. Physical mapping 3. DNA sequencing Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

5. Fig. 21.2 Cytogenetic map Genes located by FISH Chromosome bands Linkage mapping 1 2 3 Genetic markers Physical mapping Overlapping fragments DNA sequencing Identification of RFLPs, STRs, and polymorphisms. Large DNA fragments are cloned into YAC/BAC vectors and smaller fragments into phage vectors.

6. Linkage Map The starting point for the human genome project was an incomplete picture of the organization of many genomes. Geneticists had karyotypes for many species, showing the number and banding pattern of chromosomes. The locations of some genes had been identified by fluorescence in situ hybridization (FISH), in which fluorescently labeled probes hybridize to an immobilized array of chromosomes. The initial stage in the three-stage approach to mapping the human genome was to construct a linkage map of several thousand genetic markers spaced throughout each of the chromosomes. The order of the markers and the relative distances between them on such a map are based on recombination frequencies. The markers can be genes or any other identifiable sequences in the DNA, such as restriction fragment length polymorphisms (RFLPs) or simple tandem repeats (STRs). By 1992, researchers had compiled a human genetic map with about 5,000 markers, enabling them to locate genes by testing for genetic linkage to known markers. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

7. Physical Mapping of the Human Genome In a physical map, the distances between markers are expressed by some physical measure, usually the number of base pairs along the DNA. A physical map is made by cutting the DNA of each chromosome into a number of restriction fragments and then determining the original order of the fragments in the chromosomal DNA. The key is to make fragments that overlap, to identify the overlaps, and then to assign fragments to a sequential order that corresponds to their order in a chromosome. Supplies of the DNA fragments used for physical mapping are prepared by DNA cloning into YAC, BAC, and phage vectors. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

8. Complete DNA Sequence of each Chromosome The sequencing of all 3.2 billion base pairs in a haploid set of human chromosomes presented a huge challenge. This challenge was met by sequencing machines, using the dideoxy chain-termination method. The development of technology for faster sequencing has accelerated the rate of sequencing dramatically— from 1,000 base pairs a day in the 1980s to 1,000 base pairs per second in 2000. Methods that can analyze biological materials very rapidly and produce enormous volumes of data are said to be “high-throughput”; sequencing machines are an example of high-throughput devices. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

9. Whole-Genome Shotgun Sequencing The whole-genome shotgun approach was developed by J. Craig Venter in 1992. Powerful computer programs are used to order fragments into a continuous sequence The shotgun approach skips the linkage mapping and physical mapping stages and begins with the sequencing of randomly generated DNA fragments. The whole-genome shotgun method can miss some duplicated sequences, thus underestimating the size of the genome and missing some genes in those regions. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

10. Both the three-stage process and the whole- genome shotgun approach were used for the Human Genome Project and for genome sequencing of other organisms At first many scientists were skeptical about the whole-genome shotgun approach, but it is now widely used as the sequencing method of choice A hybrid of the two approaches may be the most useful in the long run

11. Scientists use bioinformatics to analyze genomes and their functions The goals of the Human Genome Project included establishing databases and analytical software, both of which are centralized and readily accessible on the Internet. –National Center for Biotechnology Information (NCBI) database of sequences is called Genbank Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

12. Centralized Resources for Analyzing Genome Sequences Bioinformatics resources are provided by a number of sources: –National Library of Medicine and the National Institutes of Health (NIH) created the National Center for Biotechnology Information (NCBI) –European Molecular Biology Laboratory –DNA Data Bank of Japan

13. Genbank, the NCBI database of sequences, doubles its data approximately every 18 months Software is available that allows online visitors to search Genbank for matches to: –A specific DNA sequence –A predicted protein sequence –Common stretches of amino acids in a protein The NCBI website also provides 3-D views of all protein structures that have been determined

14. Fig. 21-4

15. Protein-coding genes can be identified within DNA sequences Software is used to scan DNA sequences for transcriptional and translational start and stop signals, for RNA-splicing sites, and for other signs of protein-coding genes. Software also looks for certain short sequences that correspond to sequences present in known mRNAs. –Thousands of such sequences, called expressed sequence tags, or ESTs, have been collected from cDNA sequences and are cataloged in computer databases. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

16. Genes and their products can be understood at the systems level Genomics gives new insights into fundamental questions about genome organization, regulation of gene expression, growth and development, and evolution. The success in sequencing genomes and studying entire sets of genes has encouraged scientists to attempt similar systematic study of the full protein sets (proteomes) encoded by genomes, an approach called proteomics. Biologists have begun to compile catalogs of genes and proteins— listings of all the “parts” that contribute to the operation of cells, tissues, and organisms. Using these catalogs, researchers have shifted their attention from the individual parts to their functional integration in biological systems. One basic application of the systems biology approach is to define gene circuits and protein interaction networks. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

17. How Systems Are Studied: An Example A systems biology approach can be applied to define gene circuits and protein interaction networks Researchers working on Drosophila used powerful computers and software to predict 4,700 protein products that participated in 4,000 interactions The systems biology approach is possible because of advances in bioinformatics

18. Fig. 21-5 Proteins

19. The Cancer Genome Atlas is another example of systems biology in which a large group of interacting genes and gene products is analyzed together to identify how changes in biological systems leads to cancer. In a three-year pilot project running from 2007 to 2010, researchers are analyzing three types of cancer—lung, ovarian, and glioblastoma of the brain—by comparing gene sequences and patterns of gene expression in cancer cells with those in normal cells. A set of approximately 2,000 genes from the cancer cells will be sequenced during the progression of the disease, to monitor changes due to mutations and rearrangements. The GeneChip is a microarray containing most of the known human genes. The GeneChip is being used to analyze gene expression patterns in patients suffering from various cancers and other diseases, with the eventual aim of tailoring their treatment to their unique genetic makeup and the specifics of their cancers. Ultimately, all of us may carry with our medical records a catalog of our DNA sequence, a sort of genetic bar code, with regions highlighted that predispose us to specific diseases. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Application of Systems Biology to Medicine

20. Fig. 21-6

21. Genomes vary in size, number of genes, and gene density Genomes had been sequenced for 500 bacteria, 45 archaea, and 65 eukaryotes including vertebrates, invertebrates, and plants. Genomes of most bacteria and archaea range from 1 to 6 million base pairs (Mb); genomes of eukaryotes are usually larger in size. Most plants and animals have genomes greater than 100 Mb; humans have 3,200 Mb in size. Bacteria and archaea have fewer number of genes than eukaryotes. Free-living bacteria and archaea have 1,500 to 7,500 genes Unicellular fungi have from about 5,000 genes and multicellular eukaryotes from 40,000 genes. Humans have around 20,000 genes.

22. Genomes vary in size, number of genes, and gene density Number of genes is not correlated to genome size For example, it is estimated that the nematode C. elegans has 100 Mb and 20,000 genes, while humans have 3,200 Mb and 20,488 genes This lower number, similar to the number of genes in the nematode C. elegans, has surprised biologists. How do humans (and other vertebrates) get by with no more genes than a nematode? Vertebrate genomes use extensive alternative splicing of RNA transcripts. This process generates more than one functional protein from a single gene. Nearly all human genes contain multiple exons, and an estimated 75% of these multi-exon genes are spliced in at least two different ways. Additional polypeptide diversity can result from post-translational modifications. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

23. Table 21-1

24. Gene density is the number of genes present in a given length of DNA Eukaryotes have larger genomes but lower gene density than prokaryotes. The bulk of most eukaryotic genomes consists of noncoding DNA sequences, often described in the past as “junk DNA” Much evidence indicates that noncoding DNA plays important roles in the cell For example, genomes of humans, rats, and mice show high sequence conservation for about 500 noncoding regions Sequencing of the human genome reveals that 98.5% does not code for proteins, rRNAs, or tRNAs Humans have hundreds or thousands of times as many base pairs in their genome as most bacteria, but only 5–15 times as many genes—thus, the gene density is lower. In bacterial genomes, most of the DNA consists of genes for protein, tRNA, or rRNA. –Nontranscribed regulatory sequences, such as promoters, make up only a small amount of the DNA. –Bacterial genes lack introns. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

25. Eukaryotic DNA Most eukaryotic DNA does not code for protein and is not transcribed into functional RNA molecules (such as tRNAs). Eukaryotic DNA includes more complex regulatory sequences. Some of the DNA in multicellular eukaryotes is present as introns within genes. Introns account for most of the difference in average length between human genes (27,000 base pairs) and bacterial genes (1,000 base pairs). Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

26. Multicellular eukaryotes have much noncoding DNA and many multigene families The coding regions of protein-coding genes and the genes for RNA products such as rRNA, tRNA, and miRNA make up only 1.5% of the genomes of most multicellular eukaryotes. Gene-related regulatory sequences and introns account for 24% of the human genome. The rest, located between functional genes, includes unique noncoding DNA such as gene fragments and pseudogenes, nonfunctional former genes that have accumulated mutations over a long time. Eukaryotic DNA also contains repetitive DNA, sequences that are present in multiple copies in the genome. Three-quarters of this repetitive DNA (44% of the entire human genome) is made up of units called transposable elements and sequences related to them. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

27. Fig. 21.7 p434 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%) The Human Genome

28. Transposable Elements and Related Sequences The first evidence for wandering DNA segments came from geneticist Barbara McClintock’s breeding experiments with Indian corn McClintock identified changes in the color of corn kernels that made sense only by postulating that some genetic elements move from other genome locations into the genes for kernel color These transposable elements move from one site to another in a cell’s DNA; they are present in both prokaryotes and eukaryotes

29. Fig. 21-8

30. Transposable elements can move from one location to another within the genome Both prokaryotes and eukaryotes have stretches of DNA that can move from one location to another within the genome. These stretches are known as transposable elements. During transposition, a transposable element moves from one site in a cell’s DNA to another by a recombination process. Transposable elements were called “jumping genes,” but in fact, they never completely detach from the cell’s DNA. The original and new DNA sites are brought together by DNA bending. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

31. Movement of Transposons and Retrotransposons Eukaryotic transposable elements are of two types: transposons and retrotransposons Transposons move within a genome by means of a DNA intermediate by a “cut-and-paste” mechanism, which removes the element from the original site, or by a “copy-and-paste” mechanism, which leaves a copy behind. Most transposable elements are retrotransposons, which move by means of an RNA intermediate. –Retrotransposons always leave a copy at the original site during transposition because they are initially transcribed into an RNA intermediate. –To insert at another site, the RNA intermediate is first converted back to DNA by reverse transcriptase, an enzyme encoded in the retrotransposon itself. –A cellular enzyme catalyzes insertion of the reverse-transcribed DNA at a new site. Retroviruses, which use reverse transcriptase to produce their DNA, may have evolved from retrotransposons. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

32. Fig. 21.9 p435 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

33. Sequences Related to Transposable Elements Multiple copies of transposable elements are scattered throughout eukaryotic genomes Transposable elements and related sequences are usually hundreds to thousands of base pairs long, and the dispersed “copies” are similar but not identical. These sequences make up 25–50% of most mammalian genomes and even higher percentages of the genomes of amphibians and many plants. In primates, a large portion of transposable element– related DNA consists of a family of similar sequences called Alu elements Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

34. Commonly occuring transposable elements Alu elements account for about 10% of the human genome. –Many Alu elements are transcribed into RNA molecules, although their cellular function, if any, is unknown. An even larger percentage (17%) of the human genome is made up of a type of retrotransposon called LINE-1, or L1. –L1 sequences have been found within the introns of nearly 80% of the human genes analyzed, suggesting that L1 may help regulate gene expression. –Sequences within L1 block RNA polymerase. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

35. Some repetitive DNA is not related to transposable elements Repetitive DNA that is not related to transposable elements probably arose by mistakes during DNA replication or recombination. –Such duplication of long sequences of DNA accounts for about 15% of the human genome. Simple-sequence DNA contains many copies of tandemly (one right after another) repeated short sequences. Repeated units may contain as many as 500 or as few as 15 nucleotides. When the unit contains 2–5 nucleotides, the series of repeats is called a short tandem repeat, or STR. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

36. Simple-sequence DNA Simple-sequence DNA is less dense than the rest of the cell’s DNA. Much of a genome’s simple-sequence DNA is located at chromosomal telomeres and centromeres, suggesting that this DNA plays a structural role for chromosomes. –The DNA at centromeres is essential for the separation of chromatids in cell division. –The simple-sequence DNA located at telomeres, at the tips of chromosomes, prevents genes from being lost as the DNA shortens with each round of replication. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

37. Genes and Multigene Families Gene-related DNA makes up about 25% of the human genome DNA sequences that code for proteins or produce tRNA or rRNA make up 1.5% of the human genome. If introns and regulatory sequences associated with genes are included, the total amount of gene-related DNA—coding and noncoding—constitutes about 25% of the human genome. Some of the transcribed DNA occurs in multigene families, collections of two or more identical or very similar genes that are clustered together along a chromosome. –Except for genes that code for histone proteins, these families have RNAs as final products. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

38. Genes for the three largest rRNA molecules are a family of identical DNA sequences These rRNA molecules are transcribed from a single transcription unit, repeated tandemly hundreds to thousands of times in one or several clusters in the genome of a multicellular eukaryote. The many copies of this rRNA transcription unit help cells to quickly make the millions of ribosomes needed for active protein synthesis. The primary transcript is cleaved to yield the three rRNA molecules. Fig. 21.10 p437 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

39. Multigene families of nonidentical genes Multigene families of nonidentical genes are two related families of genes that encode globins, a group of proteins that include the α and β polypeptide subunits of hemoglobin. One family, located on chromosome 16 in humans, encodes various forms of α-globin; the other, on chromosome 11, encodes forms of β-globin. The different forms of each globin subunit are expressed at different times in development, allowing hemoglobin to function properly in the changing environment of the developing animal. Fig. 21.10 p437 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

40. 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 probably only had genes necessary for survival and reproduction. The size of genomes has increased over evolutionary time, and the extra genetic material promotes gene diversification. An accident in meiosis can result in one or more extra sets of chromosomes, a condition known as polyploidy. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

41. Polyploidy In rare cases, the polyploidy condition can facilitate the evolution of genes. In a polyploid organism, one set of genes can provide essential functions for the organism. The genes in the extra set may diverge by accumulating mutations. These variations may persist if the organism carrying them survives and reproduces. In this way, genes with novel functions may evolve. The accumulation of mutations may lead to the branching off of a new species (this happens often in plants). Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

42. 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 Duplications and inversions result from mistakes during meiotic recombination Comparative analysis between chromosomes of humans and 7 other mammalian species suggests that several large blocks of genes are conserved between species. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

43. Chromosomal rearrangements are thought to contribute to the generation of new species Fig. 21.11 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

44. 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 Some of the recombination “hot spots” associated with chromosomal rearrangement are also locations that are associated with diseases

45. Duplication and divergence of gene-sized regions of DNA Unequal crossing over during prophase I of meiosis can result in one chromosome with a deletion and another with a duplication of a particular region. Transposable elements can provide sites for crossover between nonsister chromatids. This produces one chromatid with 2 copies of the gene and one chromatid with 0 copies of the gene. Fig. 21.12 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

46. Unequal crossing over during DNA replication leads to duplication of genes and the emergence of multigene families The genes encoding the various globin proteins evolved from one common ancestral globin gene, which duplicated and diverged about 450–500 million years ago After the duplication events, differences between the genes in the globin family arose from the accumulation of mutations Subsequent duplications of these genes and random mutations gave rise to the present globin genes, which code for oxygen- binding proteins The similarity in the amino acid sequences of the various globin proteins supports this model of gene duplication and mutation Fig. 21.13 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

47. Table 21-2

48. Evolution of Genes with Novel Functions In some gene families, one copy of a duplicated gene can undergo alterations that lead to a completely new function for the protein product. Example: The genes for lysozyme and  -lactalbumin –The two proteins are similar in their amino acids sequences and three-dimensional structures but have totally different functions 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

49. Rearrangements of Parts of Genes: Exon Duplication and Exon Shuffling Fig. 21.14 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings The duplication or repositioning of exons has contributed to genome evolution 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 gene with the duplicated exon would code for a protein with a second copy of the encoded domain, thus changing protein’s structure and function.

50. How Transposable Elements Contribute to Genome Evolution Multiple copies of similar transposable elements allows for 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

51. Transposable elements may carry a gene or groups of genes to a new location Transposable elements may also create new sites for alternative splicing in an RNA transcript In most cases these genetic changes are usually detrimental but may on occasion prove advantageous to an organism How Transposable Elements Contribute to Genome Evolution Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

52. Comparing genome sequences provides clues to evolution and development Comparisons of genome sequences from different species tell about the evolutionary history of life and Help explain how the evolution of development leads to morphological diversity The more similar in sequence the genes and genomes of two species, the more closely related those species are in their evolutionary history. Comparing the genomes of closely related species provides information about recent evolutionary events; comparing the genomes of distantly related species sheds light on ancient evolutionary history. Relationships among species can be represented by a tree-shaped diagram Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

53. Fig. 21.15 Most recent common ancestor of all living things Billions of years ago 4 3 21 0 Bacteria Eukarya Archaea Chimpanzee Human Mouse 0102030 40 50 60 70 Millions of years ago

54. Comparing Distantly Related Species Highly conserved genes are genes that have changed very little over time and are very similar in different species These inform us about relationships among species that diverged from each other a long time ago. Bacteria, archaea, and eukaryotes diverged from each other between 2 and 4 billion years ago. Highly conserved genes can be studied in one model organism, and the results applied to other organisms –For example, scientists can utilize yeast cells to study certain human diseases because certain genes (and proteins) are so similar Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

55. Comparing Closely Related Species Genetic differences between closely related species can be correlated with phenotypic differences – What genomic information makes a human or a chimpanzee? For example, genetic comparison of several mammals with nonmammals helps identify what it takes to make a mammal Identifying the genes shared by chimpanzees and humans but not by rodents gives information about primates. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

56. Human and chimpanzee genomes differ by 1.2%, at single base-pairs, and by 2.7% because of insertions and deletions Several genes are evolving faster in humans than chimpanzees These include genes involved in defense against malaria and tuberculosis, regulation of brain size, and genes that code for transcription factors

57. Some genes evolve faster than others Biologists have identified a number of genes that are apparently evolving faster in humans than in either the chimpanzee or the mouse. These include genes involved in defense against malaria and tuberculosis and at least one gene regulating brain size. The genes evolving the fastest in humans are those that code for transcription factors. Transcription factors regulate gene expression and thus play a key role in orchestrating the overall genetic program. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

58. FOXP2 One transcription factor whose gene shows evidence of rapid change in the human lineage is called FOXP2. Several lines of evidence suggest that this gene functions in vocalization in vertebrates. Researchers are exploring whether differences between the human and chimpanzee FOXP2 proteins account for the ability of humans, but not chimpanzees, to communicate by speech. –There are only two amino acid differences between the human and chimpanzee FOXP2 proteins. Mutations in the FOXP2 gene can produce severe speech and language impairment in humans. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

59. Fig. 21-16 Wild type: two normal copies of FOXP2 EXPERIMENT RESULTS Heterozygote: one copy of FOXP2 disrupted Homozygote: both copies of FOXP2 disrupted Experiment 1: Researchers cut thin sections of brain and stained them with reagents, allowing visualization of brain anatomy in a UV fluorescence microscope. Experiment 2: Researchers sepa- rated each newborn pup from its mother and recorded the number of ultrasonic whistles produced by the pup. Experiment 1Experiment 2 Wild typeHeterozygoteHomozygote Number of whistles Wild type Hetero- zygote Homo- zygote (No whistles) 0 100 200 300 400

60. Comparing Genomes Within a Species As a species, humans have only been around about 200,000 years and have do not have much 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

61. 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

62. Widespread Conservation of Developmental Genes Among Animals Molecular analysis of the homeotic genes in Drosophila has shown that they all include a sequence called a homeobox An identical or very similar nucleotide sequence has been discovered in the homeotic genes of both vertebrates and invertebrates Homeobox genes code for a domain that allows a protein to bind to DNA and to function as a transcription regulator Homeotic genes in animals are called Hox genes, or homeotic genes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

63. Hox genes are conserved between a fruit fly and a mouse Hox genes (green, orange, and brown bands in figure) that control anterior and posterior structures of the mouse and fruit fly body are very similar. These same Hox genes are also similar in yeast, plants, and prokaryotes. –Similar in sequence –Similar chromosomal arrangement Fig. 21.17 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

64. How can Hox genes be involved in the development of animals whose forms are so different? Small differences in the regulatory sequences of particular genes cause changes in gene expression patterns that can lead to major changes in body form. The differing patterns of expression of the Hox genes along the body axis in insects and crustaceans explain the variation in the number of leg-bearing segments among these segmented animals. The same Hox gene product may have different effects in different species, turning on new genes or turning on the same genes at higher or lower concentrations. Fig. 21.18 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

65. In addition to hox genes, many other developmental genes are highly conserved from species to species. Related homeobox sequences have been found in regulatory genes of yeasts, plants, and even prokaryotes In addition to homeotic genes, many other developmental genes are highly conserved from species to species Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

66. Comparison of Animal and Plant Development In both plants and animals, development relies on a cascade of transcriptional regulators turning genes on or off at specific times Mads-box genes in plants are the regulatory equivalent of Hox genes in animals –Although Hox genes can be found in plants and Mads- box genes in animals, the genes do not perform the same major roles in development in both groups. These types of differences support the theory that evolution of developmental programs in plants and animals occurred separately Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

67. Fig. 21-UN1 Bacteria Archaea Genome size Number of genes Gene density Most are 1–6 Mb 1,500–7,500 Higher than in eukaryotes Introns None in protein-coding genes Other noncoding DNA Very little Present in some genes Can be large amounts; generally more repetitive noncoding DNA in multicellular eukaryotes Unicellular eukaryotes: present, but prevalent only in some species Multicellular eukaryotes: present in most genes Lower than in prokaryotes (Within eukaryotes, lower density is correlated with larger genomes.) 5,000–40,000 Most are 10–4,000 Mb, but a few are much larger Eukarya