The Making of the Fittest: The Birth and Death of Genes

1. The Making of the Fittest:The Birth and Death of Genes The Molecular Evolution of Gene Birth and Death Author: Ann Brokaw AP Biology Teacher Rocky River High School Rocky River, Ohio

2. The Birth and Deathof Genes To the student: The following slides provide examples of how genes can be gained and lost through evolution. Answer the questions on the student handout when prompted.

3. The Birth of Genes Mutations are the ultimate source of new genes. A mutation is a change in an organism’s genetic information, or DNA. Mutations occur at random. When mutations occur in genes, they may result in new phenotypes that natural selection acts upon. Student Handout:Answer Question 1

4. Heritable Mutations Mutations can occur at any time and in the DNA of any type of cell. Mutations that occur in somatic (body) cells only impact the individual in which they occur. Mutations that occur in gametes (egg and sperm) can be passed on to the next generation. Student Handout:Answer Question 2

5. Types of Mutations Mutations can occur on a small scale, most often affecting one or two nucleotides of DNA, or can involve large segments of a chromosome or even an entire chromosome. Regardless of the type, mutations in a gene’s DNA can alter the function of the protein encoded by the gene.

6. Point Mutations Most mutations involve changes to a single nucleotide or a few nucleotides of an organism’s DNA. Point mutations are changes in a single nucleotide of the DNA sequence. They include substitutions, insertions, and deletions. Insertions and deletions are not only point mutations; they can involve two or more nucleotides. Student Handout:Answer Questions 3 - 4

7. Substitutions A substitution mutation is the replacement of a single nucleotide with another. It can be classified in one of three ways depending on the effect it has on the protein produced: • Silent mutations have no effect on the protein. • Missense mutations result in a single amino acid change in the translated sequence. • Nonsense mutations result in an amino acid codon being replaced by a “stop” codon.Nonsense mutations cause a premature end to translation, resulting in a truncated protein.

8. Substitution Examples Student Handout:Answer Questions 5 - 6

9. Sickle Cell Anemia Sickle cell anemia is a disease caused by a point mutation that affects the shape of red blood cells. People with sickle cell anemia, which is also called sickle cell disease, experience frequent pain, infections, and other symptoms. Click to view an animation on sickle cell anemia From the BioInteractive.org website: http://www.hhmi.org/biointeractive/dna/DNAi_sicklecell.html A. B. C. Student Handout:Answer Question 7

10. Rett Syndrome Rett syndrome is a disorder that primarily affects girls and causes severe problems with communication, learning, and coordination. The most common cause of Rett syndrome are mutations in the MECP2 gene on the X chromosome. This gene provides instructions for making a protein that is critical for normal brain function. Click to view a lecture clip on Rett syndrome From the BioInteractive.org website: www.biointeractive.org/neuroscience/ child_dev+rett.html A. A. B. B. C. C. D. D. Student Handout:Answer Question 8

11. Insertions and Deletions Insertion and deletion mutations occur when one or more base pairs are inserted or deleted from the DNA sequence. Since mRNA is translated three nucleotides at a time, insertions and deletions that do not involve three or multiples of three nucleotides change how all the mRNA downstream of the mutation is translated. These mutations are known as frameshift mutations. Frameshift mutations almost always result in a nonfunctional protein. Student Handout:Answer Question 9

12. Repeat Expansion Some protein-coding genes contain sequences of three nucleotides, repeated several times. This type of repeat is called a trinucleotide repeat.The number of repeats can increase, or “expand,” due to an error during DNA replication. The repeat expansion gives rise to a new allele but can still result in a functioning protein. However, if the number of repeats exceeds a certain “normal” threshold for that gene, the resulting protein will no longer function properly. Student Handout:Answer Question 10

13. Spinocerebellar Ataxia Type 1 An example of a disease caused by a trinucleotide repeat expansion is spinocerebellar ataxia type 1 (SCA1). SCA1 is an inherited disease of the central nervous system. The mutations cause malfunctioning of the nerve fibers that carry messages to and from the brain. The overall result is degeneration of the cerebellum, the coordination center of the brain. Click to view a lecture clip on spinocerebellar ataxia type 1 From the BioInteractive.org website: http://media.hhmi.org/hl/03Lect3.html?start=12:26&end26:16 Student Handout:Answer Question 11

14. Are All Mutations “Bad”? It is a common misconception that “all mutations are bad.” We have already learned that some mutations in genes have no effect, such as silent mutations, whereas others cause disease. But mutations can also be beneficial to an organism. Here is an example: View the short film The Making of the Fittest: Natural Selection and Adaptation From the BioInteractive.org website: www.biointeractive.org/shortfilms Student Handout:Answer Question 12

15. Chromosomal Alterations Changes to the number or structure of chromosomes can also affect an organism’s phenotype. Such large-scale changes most often occur during the S phase of interphase, when DNA is replicating; during prophase I of meiosis, when crossing over occurs; or upon exposure to damaging agents, such as radiation. There are four main types of alterations in chromosome structure: deletions, inversions, translocations, and duplications. Student Handout:Answer Questions 13 - 14

16. Types of Chromosomal Alterations • Chromosomal deletions occurwhen part or all of a chromosome is lost. • Chromosomal inversions occurwhen a segment of a chromosome breaks off and reattaches in the reverse orientation. • Chromosomal translocations occur whena part of a chromosome breaks off and attaches to a nonhomologous chromosome. • Chromosomal duplications occur whenpart or all of a chromosome is repeated. Student Handout:Answer Question 15

17. Cri-du-chat Syndrome Cri-du-chat is a rare disorder caused by a chromosomal alteration on chromosome 5. Infants with this condition often have a high-pitched cry that sounds like that of a cat. A drawing of an affected individual’s chromosome 5 is shown below. Student Handout:Answer Question 16

18. Chronic Myelogenous Leukemia Chronic myelogenous leukemia (CML) is a rare form of cancer caused by a chromosomal alteration that occurs in somatic cells. It is characterized by increased and unregulated growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood. Click to view a lecture clip on chronic myelogenous leukemia From the BioInteractive.org website: http://media.hhmi.org/hl/03Lect2.html?start=32:20&end36:11 Click to view an animation on CML and Gleevec From BioInteractive.org website: www.biointeractive.org/dna/DNAi_cml_gleevec.html Student Handout:Answer Question 17

19. A Closer Look at Duplications Chromosomal duplications occur when all or part of a chromosome is repeated, resulting in two copies of a gene or genes. Two genes are said to be paralogousif they exist at different chromosomal locations in the same organism and if they arose from a common ancestral gene. Gene duplication can lead to new traits and has played a major role in the evolution and diversification of life. Student Handout:Answer Question 18

20. Causes of Gene Duplications • Mechanisms by which complete genes are duplicated include: • Unequal crossing over: Chromatids from homologous chromosomes are misaligned during crossing over in prophase I of meiosis, causing one chromatid to gain a second set of genes from the homologous chromatid. • Chromosome breaks: A piece of a chromosome breaks off and becomes attached as an extra segment to another chromosome during meiosis. • Retrotransposition: mRNAs are reverse transcribed into DNA, and these reverse copies of genes are inserted at random sites in the genome.

21. Gene Duplication Outcomes • When a gene is duplicated: • one of the two gene copies can lose its function by accumulating mutations over generations. • one of the two gene copies can gain a novel function through subsequent mutation; this can only happen if the original gene duplication event does not have severe effects on the organism and can persist over generations. • the two copies of the gene can partition the total function of the ancestral gene into two unique but related functions for more efficient expression. Student Handout:Answer Question 20

22. Duplicated Genes in Animals Lysozyme is an enzyme in animals that protects against bacterial infection by hydrolyzing the cell walls of bacteria. α-Lactalbumin is a nonenzyme protein that plays a role in mammalian milk production. Both proteins have similar amino acid sequences and three-dimensional structures. They are both present in mammals, but only lysozyme is present in birds. Student Handout:Answer Question 21

23. Duplicated Genes in Flowering Plants The flowering plant genes P1 and paleoAP3 are involved in stamen development. Scientists have traced the origin of these genes to the duplication of a gene called MADS. This duplication took place prior to the evolution of flowering plants. More recently, the paleoAP3 gene duplicated again. The new gene evolved a novel function in petal development. Student Handout:Answer Question 22

24. Other Examples of Duplicated Genes The following examples of gene duplications demonstrate the evolutionary significance of these events: Human olfactory genes Early mammals carried a single gene for detecting odors; today, humans have 1,000 olfactory receptor genes. Genes that break down RNA Most primates have one gene for the pancreatic enzyme RNAse, which breaks down dietary RNA and degrades double-stranded RNA, perhaps as a defense against viruses. The colobine monkey, douc langur, has two genes that produce two RNA-degrading enzymes—RNAse1 and RNAse1B—which work best at different pH levels. Douc langurs primarily eat leaves, and the new gene improved the efficiency of digestion. Student Handout:Answer Questions 23

25. The Death of Genes Duplication can lead to new genes. But genes can also lose their protein-producing abilities or stop being expressed. Such genes are called pseudogenes, or “molecular fossils.” As species have evolved, diverged, and gone extinct, so too have their genes. Genes become pseudogenes when they accumulate mutations over long periods of time. Note that this only happens if the mutations do not compromise the organism’s survival, or else natural selection would eliminate the mutations. Student Handout:Answer Questions 24 - 25

26. Examples of Gene Death There are several examples of genes losing their functions that demonstrate the evolutionary significance of these events. Olfactory receptor genes in humans and mice Mice have about 1,500 olfactory receptor genes, while humans have about 1,000. Only 20 percent of mouse olfactory receptor genes are pseudogenes, compared to about 60 percent in humans. Myoglobin gene in some icefish species Myoglobin is an oxygen-binding protein found in muscles, similar to hemoglobin in red blood cells. Myoglobin is absent from muscles, including the heart, of several, but not all, icefish species. Student Handout:Answer Question 26

27. Gene Birth and Death in Icefish Icefish provide an excellent example of both the birth and death of genes. Click to view the short film The Making of the Fittest: The Birth and Death of Genes From the Biointeractive.org website: www.biointeractive.org/shortfilms Student Handout:Answer Questions 27 - 30

28. Evolutionary Significance ofGene Birth and Death “Natural selection acts only in the moment. It cannot preserve what is no longer used, and it cannot plan for the future.” Dr. Sean Carroll, Into the Jungle Student Handout:Answer Questions 31 - 34

29. Resources: • Campbell, Neil A. and Jane B. Reece. Biology, AP Edition. Eighth Edition. Pearson Benjamin Cummings Publishing. San Francisco, California. 2008. • Carroll, Sean B. In Cold Blood: The Tale of the Icefish, Chapter 9, Into the Jungle, Benjamin Cummings, San Francisco, California. 2008. • Deng, Cheng, et al. Evolution of an Antifreeze Protein by Neofunctionalization Under Escape from Adaptive Conflict. Proceedings of the National Academy of Sciences, Vol. 107, No. 50. December 14, 2010. • Howard Hughes Medical Institute, 2003 Holiday Lectures on Science, Learning from Patients – The Science of Medicine, Chevy Chase, Maryland, 2003. • Howard Hughes Medical Institute, Making of the Fittest: Natural Selection and Adaptation, Chevy Chase, Maryland, 2011. • Howard Hughes Medical Institute, Making of the Fittest: The Birth and Death of Genes, Chevy Chase, Maryland, 2011. • Howard Hughes Medical Institute, www.BioInteractive.org, DNA animations, Chevy Chase, Maryland, 2011. • Hurles, M. Gene Duplication: The Genomic Trade in Spare Parts. PLoS Biol. 2(7): e206. doi:10.1371/journal.pbio.0020206, 2004. • Raven, Peter H. and George B. Johnson. Biology. Ninth Edition. (McGraw-Hill Publishing. New York, New York. 2011.) • Zhang, Xhang, et al. Gene Duplication Adapts to Changing Environment.Nature Genetics (online). March 4, 2002.