Lecture Notes for 11/16 Bio 102

If you go outside and you see organisms that seem well fit/adapted to their environment, the process of their becoming fit to the environment is natural selection. Individuals can't be fit to their environment, even though they are fit to their environment, because environments are constantly changing. There are also a variety of constraints, physical constraints (they have to obey the law of physics). For ex, there is a limit to how strong and light wings can be to be best functional. Making it lighter will be better, but if too light, it won't be strong enough. There will always be compromises. There are also historical constraints. For example, the larangele nerve appeared in fishlike creatures long ago as a direct link from the brain to gills near the heart. Over millions of generations, this nerve gradually lengthened, each small step always simpler than a major rewiring, more direct route. Natural selection leads to adaptation, but can only act on variation that is already there. Phylogeny is the evolutionary history of relationships among organisms or their genes. It is portrayed in a diagram called a phylogenetic tree. Based on similarities and differences in any traits we can measure (physical and genetic traits). We can sequence DNA and see how similar it is. Each split or node represents the point at which lineages diverged. Lineages joined together in tree have descended from common ancestry. The common ancestor of all organisms in the tree is called the ROOT. Imagine a lineage that is evolving over time, it is a population, due to the evolutionary forces talked about (selection, migration, drift, gene flow). The point at which 2 lineages diverge, to say that they are now different populations and in different geographic areas, one might be more adapted to a hotter climate than another selection may be responsible for the divergence, well the split is referred to at the NODE. The lineage evolves over time through selection, drift, mutation, and gene flow. At the split, gene flow between lineages stops so that each lineage evolves independently. This node implies there is no more gene flow between the pop., and that allows them to diverge. Implies that there is very little, sporadic, gene flow. Divergence is caused by evolutionary forces. Later as time goes on, the lineages continue to split, and a phylogenetic tree emerges. A phylogenetic tree is a way to portray the evolutionary relationships of lineages. Here is an example of a primate phylogeny, and in some cases, there is time on the x-axis. Chimps and humans are more closely related than to gorillas, etc. One point about phylogenies is that the ordering is not important, but the branching pattern. The important thing is that chimps and humans are more related than anything else on that tree. Each branch can be rotated, but it doesn't matter. People often make these with the ideas that at the top is the most derived lineage, but that is not necessary to arrange the trees in any particular way. You can arrange phylogenies in many different ways, all representing the same thing. Pay attention to where two lineages come together, that represents their common ancestor. A taxon, is any group of species that we can designate or name (e.g., vertebrates). A taxon that consists of all the descendents of a common ancestor is called a clade. Clade=common ancestor and everything after it. Tetrapods is everything from here on, amniotes, mammals, etc (examples of clades). What is Phylogeny? One of the greatest unifying concepts in biology is that all life is connected through evolutionary history. The tree of life is the complete, evolutionary history of life. Knowledge of evolutionary relationships is essential for making comparisons in biology. Tree of life (all life is connected). Darwin had this idea, showing how a tree could represent all lineages on earth, and are all somehow related. Oftentimes, people would draw, humans at the top of the tree , and bacteria at the bottom, implying that, evolution is directed, which is not the case. You could say that humans have more derived traits than bacteria, but it makes no sense to put humans at the top of the tree. So modern trees of life look more different, showing all lineages that exist, and their relationship. There is this huge tree of life that shows the rleationships of all organisms on earth, but the ones we know only make a small portion on earth. There is a huge

diversity of life, and what we know only make a small proportion of it. Now we are going to go into some more details in terms of homologous traits. Phylogenetic trees are constructed basted on shared physical or genetic features. Features shared by 2 or more species that were inherited from a common ancestor are homologous. Remember phylogenetic trees are made based on these shared traits. Homologous means its shared from a common ancestor. Traits in different species that share a common origin. Implies that both species derived from a common ancestor. All these bones colored blue and whatever are from the same common ancestor. Convergent traits; but similar traits can develop in unrelated groups of organisms: CONVERGENT evolution-independently evolved traits subjected to similar selection pressure may become superficially similar. Birds and bats both have wings, but the structures that gave rise to them are not homologous. In fact, they are independent evolutionary origins of wings. The bones in the bat and bird are homologous in some parts, but the actual wing is not homologous. They may have experience the same selective pressure, which is why the wings evolved, but it isn't due to homology. Organisms that appear superficially similar, is due to convergent evolution. Sharks and dolphins have similar bodies due to evolutionary convergence, not homology. Now we will talk about ancestral vs. derived traits. A trait that was present in the ancestor of a group is ancestral. A trait found in a descendent that differs from the ancestral trait is called derived. Derived traits that are shared among a group and are viewed as evidence f the common ancestry of the group are known as synapomorphies. Here is an example of a phylogeny,, here is the last common ancestry. The ancestral trait in this phylogeny is shown in gray, the derived trait is shown in black. A derived trait is a trait found in the descendence that differs from the ancestral trait, so in this case, you are going from gray to black, and black is the derived case, and the ancestral case was gray. Another term is synapomorphy, a trait shared between two lineages, a shared derived traits, it defines the two lineages. Some more exmaples, mice and chimpanzees, you can define a bunch of groups by fur, mamary glands, claws and nails, etc. Traits may be considered ancestral or derived, depending on the point of reference. Fur is an ancestral trait for any particular group of mammals. But in a phylogeny of all living vertabrates, fur would be a derived trait found only among mammals (a synapomorphy of the mammals). Whether we define a trait as ancestral or derived depends on the point of reference. So, jaws is a trait that is ancestral to this whole group, but we can also say relative to the outgroup, to the lamprey, or a larger group, jaws are a derived trait that defines a whole group. Fur is the ancestral group of all mammals, but is is also a derived trait relative to the rest of these lineages. A derived trait that defines mammals, so it just depends on the point of reference.

Lecture notes for 1/18/13 To review, phylogenetic trees represent the evolutionary relationships among lineages and evolutionary history of the lineages. Homologous traits are traits in different lineages that share a common origin. In contrast, traits can be similar not because of shared ancestry, but because of convergent evolution. And then I introduced the concept of ancestral vs. derived traits. The definitions are shown here, and this very simple example, is that if you have this phylogengy, there are only 2 trats shown here, the black and gray, gray is ancestal, and black is derived. The ancestral is the trait common in the group's ancestor, and the derived is only in certain groups. This will be more clear in this next figure. Now we are considered all vertebrates,so the presence of eyes and a backbone, are found in all lineages in this phylogeny, all vertebrates. We know that they were found in a common ancestor, so eyes and bakcbone are ancestral. A lambrey has ancestral eyes and a backbone, but doesnt have any of the derived traits such as jaws, some have lungs, some claws/nails,etc. The trick is that when you define ancestral vs derived, you have to take into context the point of reference, and think about one group at a time, and tis time it is all the vertebrates. You can consider ancestral traits as traits found in the common ancestor. Derived traits are the traits found in the the broken off lineages. Jaws is a derived traits, and jaws is shared derived trait among vertebrates, so it is a synapomorphy. Synapomorphy is a type of homologous trait, a shared, derived trait. Homology implied similar traits because there is a common trait. Not all homologous traits are synapomorphies, but all synapomorphies are homologous traits. Many organisms are considered living fossils, ginkos, horseshoe crab. Ginkos from a million years ago look a lot like the ones today, but even though the ginkos look very similar to the ones back then, they are not the same. All lineages are combinations of ancestral and derived traits, so if we go back here, the lampreys are characterized by eyes and a backbone, they do not have the other derived traits, but there are other traits they have accumulated over time. All lineages are a mixture of ancestral and derived traits. The same concept goes for horshoe crab today, they dont represent the exact ones of the back in the day. To explain a little further. This is a phylogeny of ants, the martialis (looks like from mars) is considered the first branch on the phylogeny of all the ants, so the suggestion is that it has a lot of ancestral ants, it is one of the living fossils, but does this look like the original ant? No, it was named because it looks weird. It may retain many traits ancestral to all ants, but it also has some derived traits relative to the original ants that existed. Living fossils are combos of ancestral and derived traits just like the rest of us. Evolution continues for all lineages: some traits and lineages may experience mainly stabilizing selection and remain constant for long periods (living fossil traits stay for many generations). Other traits and lineages may experience mainly directional selection and change rapidly. It doesn't make sense to say some lineages are more highly evolved, because evolution is always ongoing in every lineage. How are Phylogenetic trees constructed? Phylogenetic trees are typically constructed using hundreds or thousands of traits. Any trait that is genetically determined, and therefore heritable, can be used in a phylogenetic analysis. Traits such as the fossil record is useful for dating fossils, and that helps us to understand when certain branches and phylogenies occurred. Any trait that is genetically determined, and therefore heritable, can be used in a phylogenetic analysis. All kinds of traits-morphological, behavioral-are used to contrust phylogenies. Phylogenes show the evolutionary relatioships among lineages. Here is an example of HIV and other related viruses found in different primates, there is 2 types of HIV found in humans, but they are not closely related (one from chimpps, and one from monkeys). If you did not look at a phylogeny like this, you might not realize hat there are 2 types of

HIV. We can also look at more potentially closely related thins like viruses. WE can do this with flue, and see where they came from ancestrallyand geographically. How does phylogeny relate to systems of classification? The biological classification system was started by Swedish biologist Carolus Linneaus in the 1700's. Every species has two name: the genus (group of closely related species) to which it belongs, and the species name (e.g Homo sapiens). In the system, every organism has a genus and a species, and the genus is always capitalized, and the species name is not capitalized (sapeans). There is a whole system above that going from species , genus, Family, Order, Etc, but an important point is that species actually have a meaning, everything above is just arbitrary. Ideally the grouping above species level reflect evolutionary lineages, but they don't always. Unlike populations and species, higher taxonomic categories are arbitrary. How does phylogeny relate to classification? Taxa are expected to be monophyletic=a clade: one taxon contains an ancestor and all descendents of that ancestor, and no other organisms. A clade is all lineages that shared a common ancestor, and al the descendents after that. Clades are monophyletic. The definition of a monophyletic group (same as clade) is a groups that contains an ancestory and all derivative lineages. The problem in taxonomy, if you wanna name groups, is they often give names to groups are not monophyletic. So for example, this grouping containing E,F, and G, because just E and F are monophyletic, but adding G makes it not so. In one way to tell if you have a monophyletic group, a single cut on the evolutionary tree will remove a monophyletic group, so if you remove G, you get the real monophyletic group. E,F, and G is a a polyphyletic group that does not inlude the common ancestor of the group or all of its descendents. A paraphyletic group includes the common ancestor and some, but not all, of the ancestor's descendents. A monophyletic group contains the common ancestor and all of the descendents of that ancestor. A monophyletic group can be removed with a single cut. Why would you create groups that are not monophyletic. If you know the phylogeny, you are set, but in that past that people created taxonomic groups based on what they thought similarity between organisms were; made such strange groupings.Ex: Here is the phylogeny of vertebrates, and most of the things we call reptiles and birds, most people would combine lizards and crocodiles as reptiles, but this reptile grouping is not a monophyletic groups, because it includes birds too. It does not reflect evolutionary history. If you wanna call things reptiles, you need to include birds to lizards and crocodiles. To most people and the people that named the groups retiles in the past, lizards and crocodiles look similar, but birds dont to them, but they are close relatives to such species. Birds have keratinous scales on their legs. Grouping of lizards and crocodiles would be paraphyletic. Speciations: 3 concepts. Two modes of speciation (allopatric and sympatric-same-speciation). Speciation that occurs between reproductive isolating mechanisms (prezygotic, and postzygotic). What are species. The concept of species sometimes varies among different biologists. Most of the species concepts proposed by biologists are not mutually exclusive-just different ways of approaching the question what are species? There has historically been many species concept, and which makes most sense to use depends on which lineage you are studying. Many species concepts overlap. Linnaeus described species based on their appearance-the morphological species concept. Members of species look alike because they share many alleles. This makes sense, because things that look the same share genes. So grouping things by how the look is going to reflect evolutionary history, but members of the same species often don't look the same due to variation. And members of different species often do look the same. Here are male redwinged blackbirds from NY and British columbia are different species but look the same. But sometimes males and females of a species may be different, and immature individuals may not look like their parents. Cryptic species are morphologically indistinguishable but to not interbreed. Another problem is that females in birds often look very different, so if you go off of how the organism looks, this is the same species, according to the biological species concept, everyone recognizes it s a female redwinged blackbird, but it doesn't look like it. SO this is a flaw in linnaeus morphological concept. Another species concept that's really focused on evolutionary relationships is the linneage species concept; species are branches on the tree of life. Speciation: one species splits into

two or more daughter species, which thereafter evolve as distinct linneages. It fits exactly with the concept of phylogeny. Long term isolation of lineages is a consequence of reproductive isolation: when two populations can no longer exchange genes. So when linneages split, that by this definition, is a speciation event. Each branch in the phylogeny is a species according to this definition. This spliting of branches is due to the cessation of gene flow between the two lineages, in which they are reproductively isolated, and there is no longer changing any genes, so there is no longer reproduction between the two lineages. The biological species concept: in order for organisms to be in the same species, they have to be able to breed or have the potential to breed (you might have 2 geopgrafically isolated populations that never breed, but they could). They are groups of actually or potentially interbreeding populations which are reproductively isolated from other such groups. This concept does not apply to organisms that reproduce asexually (e.g. bacteria) and it is limited to a single point in evolutionary time. The lineage concept species make more sense for bacteria. So the point is that depending on what organism you study and your question, that might change the species concept you will want to use. Significant reproductive isolation between species is necessary for lineages to remain distinct through evolutionary time. The evolution of reproductive isolation is important for understanding the origin of species. Process of speciation, the splitting of lineages, to where they are considered to be different species, is all about the evolution of reproductive isolation, where gene flow between two populations stops, and when gene flow stops, according to biological species concept, we consider those two groups to be different species. How can reproductive isolation evolve? Not all evolutionary change results in new species. Speciation usually requires the evolution of reproductive isolation within a species whose members formerly exchanged genes (gene flow). So how can one lineage ever be split into two reproductively isolated species? The main mechanism that is thought most speciation events occur is allopatric speciation, allopatrick (allo=other, patrick=place) is just the physical separation of 2 populations. That is what can lead to the stopping of gene flow between the two population, and its also known as geographic speciation. Sympatric speciation, where populations are in the same place, but still somehow diverge (rare). Allopatric speciation occurs when populations are separated by a physical barrier (geographic speciation). Thought to be the dominanat mode of speciation in most groups. The main mechanism that is thought most speciation events occur is allopatric speciation, is what can lead to the stopping of gene flow between the two population, and then there is geographic speciation. Initially, a big blue blob represents a population where interbreeding and gene flow occurs, but there is a physical barrier (a mountain or a lake), and that physically prevents organisms from mating with each other. Sub populations will arise over time due to selection, mutation, and genetic drift, and then later on, this barrier may go away, and at some point, these two divergent lineages may come back into contact. What happens to them when they come into contact will tell if they will maintain being separate species/lineages or not. This area of contact between two separate lineages that have diverged is called a hybrid zone. The basic model of allopatric speciation is simple, if a continual population is split, gene flow stops, and the populations diverge, and when they can no longer potentially breed, they are called separate species. Sympatric speciation is different in which it is a partition of a gene pool withot physical isolation. This can occur when certain genotypes have a preference for distinct micro-habitats where mating takes place. It is when organisms in the same place diverge without physical islation. There are a few ways that this can happen, but it is very difficult to prove such speciation. One way is when certain genotypes prefer a different habitat. A case is where that certain geneotyes prefer to eat a specific food, they go to that food source and mate on that food source. And another genotype prefers mating on an alternate food source. Because there are habitat preferences, that goes along with mating, these two lineages, these two genotypes, can diverge and lead to sympatric speciation. An example is apple maggot flies. Ancestrally they only laid eggs on hawthorne fruits, but apples were introduced, and some genotypes started laying eggs on fruits and mated on the apple. There are a group of apple maggot flies

laying eggs on hawthorne fruits, and another on apples, and they mated on where ever they laid their eggs, so over time, these groups were not exchanging genes or mating. Although they existed in the same place, they had a habitat preference, so they diverged to the point that they cannot breed. Can changes in timing of mating lead to sympatric speciation? Yes. Within a population, where half mates in spring, and half in the fall; if that happens, divergence can happen rapidly over time even though they coexist in the same place. What happens when newly formed species come together? Reproductive isolating mechanisms include prezygotic reproductive barriers (act before fertilization to prevent mating) and postzygotic barriers (act after fertilization to prevent the development of viable offspring, or fertility. Now we will talk about the reproductive barriers, what stops the exchange of gene flow between two divergent lineages. There are different timing points that those barriers can happen. Prezygotic reproductive barriers mean before the egg and sperm (fertilization) comes together, there is a barrier. Postzygotic barriers are after fertilization, so it is all about timing. In Prezygotic reproductive barriers include habitat isolation (apple maggot flies), temporal isolationmating periods do not overlap. In sympatric populations of three closely related leopard frogs each species breeds at a different time of the year. There are many pre-and post zygotic barriers that can happen. One is habitat isolation (apple maggot flies). If 2 lineages are using different habitats and mating in different habitats, then they don't come in contact with each other and cant mate. The other one is temporal isolation, if organisms don't mate at the same time, they cannot mate. An example is the leopard frogs (3 types) that mate at different times. This temporal isolation happens often. Most ants mate in the air, and 3 closely related species go at different times of the day for mating (prezygotic reproductive barriers). Mechanical islation (found in many insects)-differences in size and shape of reproductive organs makes mating impossible (lock and key); in plants, mechanical isolation may involve pollenators. The size and shape of reproductive organs might not match. The organs don't fit together, so there is no potential of mating; the evolution of mechanical isolation can happen very rapidly. In plants, two different lineages of plants use different pollenators (hummingbirds vs. bees). Because there are different polenators, thats analogous to this mechanical isolation. Behavioral isolation-individuals reject or fail to recognize potential mating partners. Breeding calls of male frogs quickly diverge between related species. Female frogs ignore calls from other species. Individuals don't recognize each other or there is some mating behavior that don't match up. If that happens then there is no potential for mating to occur. There are often signals that have to be recognized, and they are species specific. Postzygotic reproductive barriers include low hybrid variability (zygotes or adults have low survival rates) and hybrid infertility (offspring are infertile) e.g (mules). In post zygotic barrier, after mates exchange egg and sperm. This doesn't mean the zygote has to live. The term hybrid is very vague, it is used when two different lineages are mating. How far separated lineages need to be to use the word hybrid is unclear. In fact, we talked about neanderthals and humans mating (some people considered both separate species or separate subspecies). The point is that you can use the word hybrid or gene flow depending on how closely related/far apart individuals are. Some things that are closely related, you would say gene flow, things when there is mating and potential for gene flow between divergent lineages, you would use hybrid. There is often low hybrid viability, where even the zygote doesnt live. Sometimes there is complete infertility. With the mule, the fertilized egg grows to an adult, but they are infertile. So as a review: Prezygtic barriers: habitat, behavioral, temporal, mechanical, and gamete isolation; postzygotic barriers: reduced viability, reduced fertility, and hybrid breakdown. Gametic isolation is where for some reason the sperm and the egg cannot come together either physically or chemically (mechanical is that the sex organs cant come together). What happens when newly formed species come together? If hybrid offspring survive poorly, natural selection may favor prezygotic barriers. Individuals that can avoid mating with members of another species would have a selective advantage. Strengthening of prezygotic barriers is known as

reinforcement. This is a pretty simple, important concept. Two lineages diverge, and they can mate, but what happens after they mate, after the hybridization. If hybrids have low survival, there can be selection for those lineages not to reproduce. IF offspring do very well, it doesn't matter if you mate in or outside population. And if they don;t survive well, its a sign not to mate with them. What happens when the lineages come together and start hybridizing? If the offspring dont do well/are inviable, there is reinforcement, selection to increase the reproductive isolating mechanisms (red lineage+blue lineage, and their offspring don't do well, then they wanna recognize each other as being a separate species and don't wanna mate. There can be fusion if in fact the offspring do well, then it doesnt matter who they mate with, and the diverged lineages may come together and form one lineage. There can also be stability of the hybrid zone if the hybrids do ok, but have intermediate fitness (they do ok). Or the two lineages are separate, with a small hybrid zone (small # of hybrids produced), so there can be different outcomes. Lineages can continue to diverge, or come back togeher, or stay with continual hybrids being produced. sin

Postzygotic barriers: Zygotic mortality: The egg is fertilized, but the zygote does not develop. Hybrid inviability: Hybrid embryo forms, but is not viable. Hybrid sterility: Hybrid is viable, but the resulting adult is sterile. Hybrid breakdown: First generation (F1) hybrids are viable and fertile, but further hybrid generations (F2 and backcrosses) are inviable or sterile.

11/23/2013 Lecture A bit of review now. Morphological species concept; members of species look alike because they share many alleles (cryptic species contradicts this)Lineage species concept; species as branches on the tree of life/phylogeny (works for bacteria). Biological species concept: groups of actually or potentially interbreeding populations which are reproductively isolated from other such groups. Organisms that can potentially breed together are the same species. Breed is pretty vague, it means sort of a lineage, but breed is usually referred to as a sub group of species (like dogs); same species, different lineages. So we talked about allopatric speciation (primary form of speciation). Starts with initially a population thats physically separated, and the 2 populations can diverge through evolutionary forces, and later on if the barrier is lost, a hybrid zone occurs where the populations come back together. What happens in the hybrid zone determines if they turn back to one species, or diverge into 2 species, or whether the hybrid zone is stable. We also talked about mechanisms for reproductive isolation (prezygotic vs. postzygotic). Question: Which of the following is false? E. The differences between gorillas and chimpanzees accumulated over the course of approximately 10 million years of evolution. Which two evolutionary forces contribute to the inevitable divergence of the two split populations separated by a mountain range? Selection, mutation, and genetic drift. So lets talk about genes and genome. Genomes are simply the full set of genes (protein coding regions) plus the non-coding regions of DNA (for some viruses it is RNA). In eukaryotes, most genes are on the chromosomes in the nucleus, but some are in mitochondria and chloroplasts. Let's define genes, because there are different definitions, but its usually protein coding regions that give rise to proteins. There are also organelles that contain DNA as well (mitochondria and chloroplasts). The DNA alphabet, different letters (ATGC), and whats often called the central dogma of molecular biology/genetics; DNA that gives rise to mRNA through transcription, which is translated into protein through translation. Another flow of info that can occur is through DNA replication. Information doesn't do the reverse of the dogma (protein, to mRNA to DNA). I want to make a point that the definition of dogma does not fit here (a principle/set of princicples laid down by an authority as incontrovertibly true). Nothing in science is incontrovertibly true, but there are not really authorities. Science is built on being skeptical and testing, and we can always find evidence that undo what we say before. 21 years ago, the human genome project started, a monumentous porject in sequencing. The result of that and many other sequencing projects is a string of letters (3k base pairs, 3.1% of human genome). What can this tell us? Well, remember that different strings of 3 nucleotides (codons) are transcribed and translated into amino acids, and there is redundancy in the genetic code (3 codons can give the same amino acids hen translated). SO a small portion of the DNA is involved in the direct transcription and translation to proteins, representing of 1.5% of all of our DNA involved in protein coding (21k genes, aprox), depending on the definition of a gene, where here we say it is a region of DNA that codes for a protein. A good question is, what is the purpose of the other DNA? Why is only 1.5% of DNA coding proteins. WE compare human genome to genome of closer relatives, like mammals. What are some genes conserved across these mammals, and what aren't. The ones vital for existance would of course be conserved, a core set of genes that have very basic functions. This is one approach, and you find that 5% of the human genome is conserved across mammals. You can make the assumption that because it is conserved, it has an important function. And you can take that as a lower bound for the amount of DNA that has a function. We assume that is has an important function; only 5%. What is the other 95% doing, and what is that other 5% doing if not encoding genes? Well, the 5% can regulate the expression of genes (operon, enhancer, silencer, etc). There is a variety of ways DNA can regulate the expression of protein coding regions. Don't remember the details of all the ways DNA can regulate expression. These different blocks represent protein coding regions (exons that will be transcribed). The dots show the regulating expression regions of the DNA (Promoter, enhancer). Keep in mind that

regions regulating the expression of any given gene can be close by, but they can also be far away as well.. There is a wide array of regulatory elements that affect whether a gene is expressed/transcribed or not. Since the human genome, there is a huge project called ENCODE (encyclopedia of DNA elements). The purpose of this was to look further at the purpose of the 98.5% of DNA that is noncoding, and how much of that DNA may be functional? It could do nothing, junk DNA, where you keep junk in the room, but garbage is what you throw away (it might do something). WE are still not sure what a lot of the DNA is doing, but more is doing stuff that we know. Approx 80% is transcribed with no known function. If you use the definition of function (any biochemical activity, being transcribed), then 80% is functional. 20% binds to regulatory proteins (18.5%) or encodes proteins (1.5%). The encode could help us find clues on what some of our DNA is doing. Some could just be there from past events, do something unknown, or not do nothing at all. 5% of human genome sequence is constrained across mammals (and presumed functional);5% of 3B bases= 150 M bases;Do not know yet the position of these 150 million functional bases;Lower bound for the amount that is functional. 1.5% encodes for protein (genes); Corresponds to 18-22k genes; many more than 22k different proteins. More than 3.5% is functional,but non-coding; gene regulatory elements, chromosomal functional elements, and undiscovered functional elements. WE would estimate 3.5% as the lower limit for functional proteins. Are protein coding regions evenly distributed? No, it spread all over. Variation between humans. 6 billion bases (3 from mom, 3 from dad). Compared to person sitting next to you, about 3-5 million single nucleotide differences, 10s of thousand larger structural differences. There is variation even on the biological level between individuals. Whole chunks of our genome could be different. Given all this variation, what does that do? Many do nothing, some are good in certain environments, and some are clearly bad (some of them are associated with a disease risk). You may have a dna sequence that predisposes you to something like heart disease. But there are single genes that are strongly associated with a gene. There is some common variants, or some rare genetic variants (a particular allele). Remember from one of the first lectures that mutation is the ultimate source of variation. Mistakes in DNA replication result in mutations-these are the raw material for evolutionary change. One type of mutation is nucleotide substitutions (like putting in A instead of G). What do genomes reveal about evolutionary processes? Many nucleotide substitutions have no effect on phenotype because most amino acids are specified by more than one codon (equal to set of 3 nucleotides that encodes for an amino acid). A substitution that does not change the amino acid that is specified is a synonymous or silent substitution. A substitution that does cause a change in the amino acid specified is a nonsynonymous substitution. There is redunancy, 3 different combos o letters that give rise to some amino acids. Ex: uua to uug is still leucine ( a substitution that has no affect on the amino acid). Nonsynonomous do have an effect;going from uua to uuc changes from leucine to phenylalenine, or uua to uGA is a stop signal (transcript is stopped). There is a variety of changes that can occur in nucleotide sequence that can or cant affect amino acid sequences and thus affect protein production and function. Signatures of evolution in DNA sequence; evolutionary changes are determined by comparing nucleotide or amino acid sequences among different organisms. Highly conserved regions are constrained, divergent regions are not. You can compare, lineup, different lineages, and compare directly their amino or DNA sequence to look for regions of the sequence that is highly conserved or highly variable. Regions conserved across lineages are assumed to have important function, whereas regions highly variable are less important (experiencing diversifying selection). Our genome sequence is the notebook, comparing close lineages and having close idea just by comparing DNA sequence what kinda selection has been going on, being highly conserved or divergent. For the last 3.5 million years, evolution has been taking notes ,and the genome is the notebook. You can compare the close lineages,and have some idea just by comparing the dna sequences what type of selection occurred; whether regions are highly conserved or divergent. You can compare the relative rate of sononymous

and nonsononymous mutations, differing depending on what kind of selection. Relative rates of synonymous and nonsynonomous substitutions should vary in genes undergoing different types of selection. If an amino acid replacement is neutral with respect to fitness, the two rates are expected to be similar (close to the same number); the ratio would be close to one. We expect the two rates to be aprox the same number, and the ratio of the two to be close to 1. In contrast, if the amino acid position is under positive selection for change, the rate of nonsynonomous substitutions should be much higher than sononymous. If there is contrast for change, postitive selection. People use slightly different terms for molecular evoluton (positive selection), whereas if talking about traits, it is directional selection. If there is selection for an protein to change, there is positive selection for that change, and we would expect more nonsynonomous substitutions than otherwise, because the NS changes are the ones changing the protein sturcture, so the NS:S would be higher than 1 in the ratio; more changes that would do something to accumulate. Finally, if an amino acid position is under purifying selection, the rate of synonumous substitions should be much higher than sononymous. This is analogous to balancing selection. If you compare human, to chimp, to mouse, DNA there are some regions that are the same, highly conserved, that experienced purifying selection, the idea that any change to that DNA sequence at all is bad for the organism and causes it to die. So purifying selection means there is no change, and we expect more S than NS substitutions, very few NS (fiddling with proteins is bad in this case). Just by comparing the number and proportion of NS to S changes, you have some kind of idea of what kind of selection has been going on. You can see a stretch of amino acids across plants, rice, up through mammals, and humans. Even across such a wide comparison, you find regions that are completely invariant, that experienced purifying selection (any change that is not goo for the organism). Then there are areas that are variable, wheer the constraint is not so strong across the regions. Some regions of the genome are experiencing strong purifying selection, others are experiencing other types of selection.

11/25 Lecture Notes Today we will finish talking about the evolution of genomes, and then talk about the history of life on earth. Back to the question asking about how orangutans may be expected to look more like the last common ancestry of all great apes than chimps and humans, and it doesn't make sense unless asking about specific traits. You can imagine scenarios where it would be true, but after these lineages split, the orangutan lineage has been evolving over time just like the others have, so you would expect like the ants and living fossils example that each species would include derived and ancestral traits. The orangutan has been evolving just as much as chimps and humans have, even if the splits were at different times (so the timing of branching doesn't matter in terms of similarity measures with the original ancestor). When changing one nucleotide does or doesn't make a difference. Remember that synonumous changes are changes in DNA sequence that does not affect the DNA sequence (gives you the same amino acid sequence), nonsynonymous does change the amino acid, and changes the whole sequence potentially. So, if NS# (no affect on AA) is = to #S and NS/S=1, and the number of changes to changes is the same, then the changes are neutral. For positive selection, NS/S>1, where changes are expected. And for purifying, where NS is bad, only S will accumulate, so N/S