Evolution and Population Genetics Notes PDF

Process of Evolution Modern organisms have descended from ancient ancestors Responsible for both the remarkable similarities across all life and the amazing diversity of that life Genetic variation upon which selective forces can act in order for evolution to occur. A population evolves becau...

Process of Evolution Modern organisms have descended from ancient ancestors Responsible for both the remarkable similarities across all life and the amazing diversity of that life Genetic variation upon which selective forces can act in order for evolution to occur. A population evolves because the population contains the collection of genes called the gene pool. As changes in the gene pool occur, a population evolves. Microevolution vs. Macroevolution The term “microevolution” applies to evolutionary change within a lineage, It occurs continuously. Depending upon the organism and the circumstances, it can transform a lineage, dramatically over time. Alternately, a lineage may appear to remain the same over time-this is called stasis. Macroevolution is the origin and extinction of lineages. It can happen gradually, or slowly. Both processes are essential to evolution. Microevolution is probably better understood, and better documented, because in some organisms it takes place on timescales we can study directly by experiment and direct observation. The Population is the Basic Unit of Microevolutionary Change The genotype of an individual is, essentially, fixed at birth. The population is the smallest unit where evolutionary change is possible. Unlike individuals, populations permit the origin of new alleles through mutation, and the change in the frequency of alleles through selection, genetic drift, etc.. Individuals do not evolve; populations and species evolve. Population Genetics Population genetics refers to the study of evolution via the observation and modeling of allele frequencies and genetic change in populations of organisms. There are three parameters to keep in mind: allele frequency: the proportion of a specific allele at a given locus, considering that the population may contain from one to many alleles at that locus. genotype frequency: the proportion of a specific genotype at a given locus, considering that many different genotypes may be possible. phenotype frequency: the proportion of individuals in a population that exhibit a given phenotype. Phenotype Frequencies To calculate the frequency of a phenotype, count the number of individuals with that phenotype, and divide by the total. Genotype Frequencies To calculate the frequency of a genotype in the population, find the total number of individuals in the population with that genotype, and divide by the population size, N. f(AA)= #(AA)/N f(Aa)= #(Aa)/N f(aa)= #(aa)/N Allele Frequencies By convention, the frequency of the dominant allele is called p, thus the frequency of the recessive allele, q=1-p. To calculate the frequency of an allele in the population, add the total number of homozygotes for that allele to half the heterozygotes, and divide by the population size, N. p= ((#AA) + (1/2)(#Aa))/N q= ((#aa) + (1/2)(#Aa))/N If you already know the genotype frequencies, p=f(AA)+(1/2)f(Aa) q=f(aa)+(1/2)f(Aa) Evolutionary Change is a Consequence of Changes in Allele Frequencies This is the genetic definition of evolution…a synthesis between Mendel’s and Darwin’s theories. All of the evolutionary change between our single-celled ancestors and ourselves can be described as the sequential origin of new alleles, their replacement of old ones, and occasionally the origin of new genes through duplication. Evolution as Change in Allele/Genotype Frequency Microevolutionary change is inherent in the change in the frequencies of alleles over time. To be able to see if evolution IS occurring, we need to consider what we would expect if evolution IS NOT occurring. Once we know that, then if we see a departure, we know that evolution is occurring. The Hardy-Weinberg Equilibrium Hardy-Weinberg Equilibrium is defined as the situation in which no evolution is occurring. It is a genetic equilibrium. It was the solution to a nineteenth century misconception-the notion that the dominance or recessiveness of an allele alone could cause evolutionary change (it can’t). The Hardy-Weinberg Equilibrium refers to a particular locus: one locus may be undergoing rapid allele-frequency change, while other loci are in equilibrium. Assumptions of the Hardy-Weinberg Equillibrium A locus with two or more alleles will be in Hardy-Weinberg Equilibrium if five assumptions are met. These are: infinite population size (there are infinitely many individuals in the population.) no allele flow (i.e., no movement of individuals from population to population.) no mutation (no biochemical changes in DNA that produce new alleles.) random mating (this means that with regard to the trait we're looking at, individuals mate at random they don't select mates based on this trait in any way.) no Selection: the different genotypes (for the genetic trait we're studying) have equal fitness. Consider a population of diploid, sexually reproducing individuals. Imagine a gene with two alleles, A and a, so there are three genotypes, AA, Aa, and aa. Assume this population meets the five assumptions of Hardy-Weinberg Equilibrium. Because mating is random, alleles mix together at random. Because the population is infinitely large, the probability of getting a gamete with a particular allele in it is simply the frequency of that allele. Similarly, determining the probabilities of getting particular genotypes will tell us the frequencies of those genotypes in the population. To get AA, you need an egg with allele A, with probability p, and a sperm with allele A, also with probability p. The probability of getting both of these is p2 Similarly, for aa, the chance of a sperm with an "a" allele is q and the chance of an egg with an "a" allele is also q, so: q2 There are two ways of getting the heterozygous genotype, Aa. These are: 1. an "A" bearing sperm and an "a" bearing egg 2. an "A" bearing egg and an "a" bearing sperm The probability of an "A" bearing sperm is p; the probability of an "a" bearing egg is q, so the probability of the first way of getting an Aa is (p)(q) = pq. Similarly, the probability of aA (a sperm, A egg) is also (p)(q)=pq. So to get the probability of getting the Aa genotype, we add together the probabilities of the two ways of getting this genotype. So: The genotype frequency of Aa is pq+pq=2pq As long as the conditions of the Hardy-Weinberg equilibrium are met, allele frequencies will remain constant. After one round of random mating, there will exist a stable, mathematical set of genotype frequencies for any given allele frequencies. This relationship will hold as long as the conditions of the Hardy-Weinberg equilibrium are met. This means that if you know allele frequencies, you can solve for expected genotype frequencies. If you know the frequency of a recessive genotype, you can usually infer the expected frequency of the recessive allele as well.  Question The albino color in rabbits is caused by a recessive allele. Aa and AA individuals are normally pigmented, and aa Freq Recessive phenotype 1/10000=.0001 individuals are albino. Freq (aa) genotype, 1/10000,.0001 Imagine a population with 9999 normally pigmented q2=.0001, therefore q=(.0001)1/2 q=.01 rabbits, and a single albino rabbit. p+q=1, so p=1-.01=.99 What is the frequency of the recessive phenotype? What 2pq=(.01x.99x2)=.0198 is the frequency of the (aa) genotype? Note that while 1 in 10,000 rabbits is an albino, approximately one in Under Hardy-Weinberg equilibrium, what are the expected fifty individuals carry the allele. This is a fairly common situation for frequencies of the dominant and recessive alleles? What a recessive allele which is selected against. is the expected frequency of the (Aa) genotype?  The Chi-Square test is ideal for this: Generate expected values from HW expectations and compare them to observed values. The “null hypothesis” in this case is that the population IS in HW equilibrium, and thus, no evolution is occurring at that locus at the moment. A violation might signal that some force of evolution is at work. For instance, imagine that you had a population of river grapes Vitis riparia. There is an enzyme locus you find interesting,(could be anything, superoxide dismutase for instance). It has two codominant alleles, SODF, for fast (because DNA fragments of it migrate rapidly on a gel), and SODS for slow, because DNA fragments migrate less quickly on a gel. You don’t actually know much about evolution in this species, and you want to know if this locus is evolving. You census 1000 individuals (at least you think so, they are grapes). You get: 460 SODF SODF 23 SODF SODS 517 SODS SODS Is the population in HW equilibrium? Genetic Basis of Variation: Mendelian genetics and inheritance patterns Genetic variation and polymorphisms: Types of genetic variation (SNPs, INDEL, CNV etc) Source of genetic variation (mutation, recombination, gene conversion) Impact of genetic variation on phenotype Human genome structure and organization. Molecular Basis of Evolution: Molecular mechanisms of evolution (e.g., gene duplication, gene regulation changes). Comparative genomics and phylogenetics. Molecular evidence for evolutionary relationships and patterns. Mutation Biochemical change in DNA that one allele into another and creates alleles. It not a common event (typical mutation rates are about one mutation in a million genes passed from generation to generation ); as a result, evolution through mutation is extremely slow. Mutation is very important for evolution because, ultimately, mutation is the source of genetic variation. Other forms of evolution cannot occur without genetic variation. With regard to the fitness of alleles, mutation is random -- it may produce alleles that result in high fitness (rare) or low fitness (much more common), and the probability of a mutation is independent of an evolutionary “need” for the mutation.  A mutation is a change in the organism’s DNA. Mutations may affect somatic (nonreproductive tissue), or they may affect the germ line (reproductive tissue). Except in clonal organisms, somatic mutations cannot generally be passed on. Evolutionary biologists are interested in heritable mutations, the kind that can be passed on to the next generation. A heritable mutation changes one allele into another, sometimes creating an allele that is not already present in the population. Some mutations create dominant alleles, some create recessive or codominant alleles. Some mutations are harmful or lethal, many are totally neutral-they have no effect, a few are favorable. Whether a mutation is harmful, neutral, or favorable, depends upon its environment Some types of mutations. Point mutations vs chromosomal mutation Substitution: one nucleotide is substituted for another, frequently this causes no change in the resulting organism, sometimes the change can be dramatic. Insertion: DNA is inserted into a gene, either one nucleotide or many. Sometimes, entire genes are inserted by viruses and transposable elements. Deletion: DNA bases are removed. Small insertions and deletions can inactivate large stretches of a gene, by causing a frame shift that renders a gene meaningless. Duplication: an entire gene is duplicated. Transposition: DNA is moved to a new place in the genome, frequently this happens because of errors in meiosis or transposable elements. Mutations are random events: their occurrence is independent of their selective value - i.e., they do not occur when they are needed any more often than they would otherwise. Mutations at any single locus are rare events: mutation rates at a typical locus are about 1 in 106 gametes. Since each individual has thousands of alleles, the cumulative effect of mutations is considerable: Consider that each of us has about 3.5x104 loci, and the mutation rates are about 1x10-6 per locus, thus, about 1 in 30 of our gametes has a new mutation somewhere in its genome. That means about 7% of us are mutants, more or less. YOU could be a mutant. Mutations are the ultimate source of genetic variation Mutations are the only source of new alleles (other than the occasional transfer of alleles by viruses). Mutation is thus the ultimate source of genetic variation, it creates the raw material upon which natural selection acts. Example-an interesting mutation In humans, one interesting mutation is called the CCR-delta32 allele (the locus is named CCR, it is one of many alleles at that locus) This allele codes for a 32 base pair deletion that makes the protein nonfunctional. Lacking this protein on the surface of their blood cells, homozygous individuals (it is effectively codominant) are essentially resistant to HIV-HIV cannot infect their cells. This mutation did not arise because of HIV, best we can figure, it predates the evolution of HIV by hundreds or thousands of years, and was neutral (or possibly maintained by selection induced by the bubonic plague) until HIV entered out species! Population genetics: Hardy-Weinberg equilibrium and its implications. Genetic drift, gene flow, and population structure. Natural selection and its role in shaping genetic variation. Adaptation and Evolutionary Processes: Types of adaptations (physiological, behavioral, morphological). Evolutionary mechanisms (mutation, gene flow, genetic drift, natural selection). Evolutionary theories (Darwinian evolution, modern synthesis, punctuated equilibrium). Genetic Drift Change in allele frequency by random chance. It occurs if a population is not infinite in size. In populations that are not infinitely large, there will be random error in which alleles are passed from generation, and allele frequencies will change at random. Since no population is really infinitely large, there is always some genetic drift occurring; however, the effect is very small in large populations. The effect of genetic drift is larger in small populations. Effects of Genetic Drift Does not generally result in adaptation. In a large population - it has little effect unless enormous spans of time are involved. (if vast spans of time ARE involved, the cumulative effects of drift on any species can be considerable-genetic drift is the primary mechanism for the substitution of neutral alleles over time, which is the mechanism of the molecular clock used in systematics.) In a small population - alleles can be lost (usually the rare ones) other alleles are fixed-their frequency reaches 1.0 genetic variation is lost, resulting in at population can become homozygous at many loci Genetic drift contributes to evolution in many ways by decreasing genetic diversity, it can put the population at risk of extinction its random nature increases the genetic differentiation between two or more populations this may lead to speciation if one or more populations become reproductively isolated. Genetic differentiation caused by genetic drift may change the genetic background against which new mutations act. If there is epistasis, a new mutation may be favorable in some populations and unfavorable in others. (Wright’s shifting balance theory) The evolution of human blood groups is a good example of genetic drift. Different Native American tribes show different blood group frequencies. For ex, Blackfoot Indians are mainly group A but Navajos are mainly group O. Blood group doesn’t affect survival or reproduction so the differences aren’t due to evolution by natural selection. In the past, human populations were much smaller and were often found in isolated groups so the blood group differences were due to evolution by genetic drift. Evolution by genetic drift also has a greater effect if there’s a genetic bottleneck (e.g. when a large population suddenly becomes smaller because of a natural disaster). For example, the mice in a large population are either black or grey (this doesn’t affect survival or reproduction). A large flood hits the population and the only survivors are grey mice and one black mouse. So, grey becomes the most common colour due to genetic. d Founder Effect The founder effect is genetic drift that occurs when when a few individuals, representing a fraction of the original allele pool, invade a new area and establish a new population. Examples: California Cypress-a very large population was established from a small number of individuals. Amish-a religious minority, which is essentially an isolated population, established from a relatively small number of individuals. Bottlenecks Bottlenecks are periods of very low population size or near extinction. This is another special case of genetic drift. The result of a population bottleneck is that even if the population regains its original numbers, genetic variation is drastically reduced Examples: Cheetahs -nobody knows exactly why it occurred, but cheetahs underwent an extreme population bottleneck several thousand years ago. As a result, they have very little genetic variation. Northern Elephant Seal-underwent an extreme population bottleneck resulting from fur hunting in the 19 century. Ashkenazic Jews-a religious minority in Central Europe that has rebounded from attempted genocide. Endangered Species Allele flow/Gene flow/migration Change in allele frequency that occurs because individuals move among populations. If there are different allele frequencies in different populations of a species, then when individuals move to a new population, they will change the allele frequencies in the new population. Allele flow (or gene flow) is an evolutionary force that results from migration of individuals or the dispersal of seeds, spores, etc. Allele flow can potentially cause evolutionary change, provided that: 1) the species has multiple subpopulations. 2) there are differences in allele frequency among populations, or among subpopulations within populations. Effects of Allele Flow Even small amounts of allele flow can negate genetic drift. If natural selection favors certain alleles in some populations, and different alleles in others, allele flow can oppose natural selection and prevent the evolution of genetic forms suited to each environment. If sufficiently strong allele flow will cause allele frequencies in different populations to converge on a single, population-wide mean. Allele Flow v.s. Genetic Drift When does allele flow negate the effects of genetic drift? Let us consider a whole bunch of semi-isolated populations, that exchange occasional migrants with each other; exchange of migrants is random Let m=the proportion of migrants exchanged per generation. Let N=the number of individuals in each population. Although famous, it runs several pages…. Allele flow will negate the effects of genetic drift if m>(1/(2N)). This is a very small number, one migrant every other generation is sufficient to prevent genetic drift from causing evolutionary differences among populations of a species, or subpopulations within a populations of a species. Allele flow and selection Note that allele flow can also oppose selection. On the edge of the range of a species, there might be local populations adapted to special conditions. Allele flow from a large, central population adapted to a different environment might swamp the effects of natural selection, by causing an influx of less fit alleles every generation to counterbalance the unfit alleles lost to selection. Non-random mating is evolution that occurs because individuals select mates based on their characteristics. Natural selection is evolution that occurs because different genotypes have different fitness. More about this later. Nonrandom Mating Two important patterns of nonrandom mating affect evolution: 1) Inbreeding, or mating between relatives (selfing is a form of inbreeding) 2) Assortative Mating Inbreeding Inbreeding, including selfing, is common in many species. Inbreeding was formerly common in humans, before the advent of increasingly sophisticated forms of transportation. High levels of inbreeding lead to the loss of the heterozygous genotype, although allele frequencies are not necessarily changed. Inbreeding exposes recessive alleles to selection, since they are more likely to be present in the homozygous state if the population is inbred. Inbreeding can cause a dramatic decline in the fitness of a population, possibly extinction, because many species harbor numerous deleterious recessive alleles that are effectively hidden from selection (i.e. the Florida Panther), although other species are unaffected by inbreeding (i.e., certain groups of parasitic Hymenopetera). Assortative Mating Assortative mating occurs when individuals choose their mates based on their resemblance to each other at a certain locus or a certain phenotype. Positive assortative mating occurs when like genotypes or phenotypes mate more often than would be expected by chance. Negative assortative mating occurs when similar genotypes or phenotypes mate less often than would be expected by chance. Examples : Dwarfs very high positive assortative mating, individuals with achronoplastic dwarfism pair up much more often than would be expected by chance IQ: slight positive assortative mating Height: slight positive assortative mating Redheads: moderate negative assortative mating-red haired individuals pair up less often than would be expected by chance. Natural Selection What is it? Principles of natural selection (variation, heritability, differential reproductive success). Natural selection is the differential survival and reproduction of individuals with certain traits. It acts on phenotypes. Because most phenotypes are, in part, determined by an organism’s genotype at one or several loci, natural selection has the potential to cause change in the frequency of alleles through time. Any allele that affects the ability of an organism to survive and reproduce will be subject to natural selection. In populations, natural selection operates whenever individuals in the population vary in their ability to survive and reproduce. Natural selection causes evolutionary change whenever there is genetic variation for traits that affect fitness. Darwin's grand idea of evolution by natural selection is relatively simple but often misunderstood. To find out how it works, imagine a population of beetles For Natural Selection to Operate: 1) there must be variation – some beetles are geen some are brown 2) some of the variation must affect survival and reproduction of individuals – green beetles tend to get eaten by birds & survive to reproduce less often than brown beetles. (Beetles brown have brown baby beetles because this traits has a genetic basis.) For Natural Selection to Cause Evolutionary Change 1) there must also be allelic variation for characteristics that affect fitness. What is Fitness? Fitness is the ability of an individual to survive and make copies of its alleles that are represented in the next generation. The fitness of an individual organisms is essentially the same as its lifetime reproductive success. The fitness of a genotype is the average fitness of all the individuals in the population that have that genotype. It is NOT physical performance. Differences in fitness may be due to differences in survivorship, differences in fecundity, or both. Absolute fitness vs. relative fitness. An organism’s absolute fitness is the total number of surviving offspring that an individual produces during its lifetime (its lifetime reproductive success). Some things that contribute to fitness are: its chance of living to a certain age (age specific survivorship), its number of offspring during a certain time interval (age specific fecundity). These are called components of fitness Relative Fitness For mathematical purposes, absolute fitness is standardized to get relative fitness. Imagine there are several genotypes, each codes for a different phenotype. The genotype with the highest absolute fitness has a relative fitness of 1.0 For every other genotype, their relative fitness is: absolute fitness of that genotype/absolute fitness of fittest genotype Directional Selection Most extreme phenotype is the most fit. When applied to a single locus, that means one allele becomes more common until it reaches fixation (I.e., frequency 1.0) Directional selection tends to eliminate genetic variation over time. If directional selection is to proceed for a long time, new mutations must replace lost genetic variation. In laboratory experiments, directional selection causes rapid change in phenotypes, followed by a plateau, caused by the loss of genetic variation. Example of Directional Selection: The peppered moth, Biston bettularia One of the best known cases of directional selection is the evolution of “industrial melanism” in this species. It has two forms: dark (melanic) and light. Controlled by a single locus with two alleles. Melanic is dominant, so that MM and Mm are dark, mm is light the moth rests on trees during the day, and uses crypsis as protection from predation by birds. Kettlewell (1955) showed that the two forms differ in their suceptibility to bird predation. The melanic form was rare in 1848. When it was first reported outside Manchester, it was visible against the lichen-covered trees and often eaten by birds. Museum collections indicate that by 1898, the melanic form had increased from 98% of the population Soot had darkened the trees, making the light form most visible. In rural areas with no soot, the melanic form was still rare. (Since the passage of clean air laws in Britain, the trend has reversed, and the light form is more common once again.) Stabilizing Selection Intermediate phenotypes, somewhere close to the mean are most fit. When applied to a single locus, it implies that the heterozygous genotype is most fit, and is called Balancing Selection. Generally, stabilizing selection maintains the mean value for the trait, and decreases the variation for the trait (thus, it usually decreases genetic variation). In the special case of balancing for a single locus, genetic variation is actually preserved, since both alleles will be maintained. Examples of Stabilizing Selection Stabilizing selection is probably common in nature. Birth Weight in Humans: It is well known that early mortality is highest for extreme birth weights. Both very small and very large infants suffer high mortality. Clutch Size in Birds and Parasitoids: Females that lay intermediate numbers of eggs have the highest reproductive success. Too many, and the offspring all starve. Too few, and the mother could have laid more. Called the Lack optimum, it applies to many birds, also to parasitoids. Example of Balancing Selection, and of the Differing fitness of an Allele in Different Environments: Sickle Cell Anemia in Humans Sickle cell anemia in humans is caused by an allele that causes hemoglobin to deform under low oxygen conditions, causing the red blood cell to “sickle”. Homozygotes for normal hemoglobin Hb+ Hb+ have no illness. Homozygotes for the sickle allele HbSHBShave a very serious genetic disease. Heterozygotes HbS Hb+ appear normal, but occasionally their blood cells sickle under stress. This is not particularly debilitating. In countries without malaria: There is strong selection against homozygotes for the sickle cell disease, w(HbSHBS)=0, because, they rarely survive long enough to have many offspring. The other two genotypes have a the same relative fitness w(Hb+ Hb+)=w(HbS Hb+ )=1, because carriers are essentially indistinguishable from those possessing normal hemoglobin. There is thus directional selection against the sickle cell allele. In countries With malaria: Heterozygotes for the sickle cell allele have some limited resistance to malaria, because the cells sickle and kill plasmodium within. The heterozygote is most fit w(HbS Hb+ )=1, w(Hb+ Hb+)=.90, w(HbSHBS)=0. Selection acts to balance maintain both alleles because the heterozygote is favored, this is an example of balancing selection. This explains why the original distribution of the sickle cell allele roughly matches the worldwide prevalence of malaria. Disruptive or Diversifying Selection Two or more phenotypes are most fit, but the intermediates have low fitness. - Not particularly common in nature. In most cases, it increases the variance for a trait, while not affecting the mean. Combined with assortative mating, it has the potential to form a polymorphic population. Frequency-Dependent Selection Selection can be frequency-dependent + frequency dependent selection: most common type is the most fit - frequency dependent selection: least common type is the most fit. Example-Eye-eating cichilids in Lake Victoria. Example-Color polymorphism in elderflower orchids.  Elderflower orchids have two colors, yellow and purple. Populations typically have both color morphs, generally with the yellow morph being slightly more common. Bumblebees are the primary pollinator. Like many orchids, elderflower orchids are deceptive. They advertize to bees, but offer no nectar reward. Bumblebees learn to recognize the most common morph, and learn to avoid it, giving an advantage to the least common morph. Gigold demonstrated this by experiment, planting arrays of orchids where the color morphs occurred in different frequencies. The least common morph had higher reproductive success, whichever form that was. Thus, selection is -frequency dependent. Natural Selection has been documented and studied in nature many times. Despite Darwin’s intuition, many documented examples of natural selection in the natural world show rapid evolution and a dramatic response to natural selection, rather than slow, gradual change. Interestingly, since the environment changes, selection in the real world often reverses direction and is not consistent over time and from one location to the next. The best know study of natural selection in the wild was the study of Galapagos finches by Rosemary and Peter Grant, and their colleagues. They documented dramatic changes in finch populations, in response to strong natural selection imposed by drought. The Environment affects the Fitness of Alleles Alleles may have different fitnesses in different environments. An allele that is favored in one environment may have a disadvantage in another environment. For systems of epistasis, the genetic environment may affect the fitness of an allele. The frequency of an allele may also affect its fitness. Examples: Sickle cell anemia, the Lap locus in mussels, color patterns in Heliconia butterflies, chromosomal inversions in Drosophila. Environmental change may reverse the effects of selection. Over evolutionary time, this seems to be the rule rather than the exception. Selection has no memory, no plan, and no goal. There was no special driving force in evolution to produce human beings, or anything like us. This does not exactly make us an “accident:”, more precisely, it makes us one species among billions of potential evolutionary outcomes. Selection does not act for the good of the species, nor for the good of the planet. Selection is weak against rare recessive alleles As you can see from the preceding equation, as recessive alleles become rare, selection against them becomes weaker and weaker, because most copies are likely to exist in the heterozygous state Likewise, selection in favorable of new mutations is very weak if that mutation is recessive. Favorable, recessive mutations can be lost by genetic drift before they have a chance to spread by selection. Speciation: Processes of speciation (e.g., allopatric, sympatric). Factors contributing to speciation (e.g., geographic isolation, reproductive barriers). Speciation's role in biodiversity and evolutionary history Mutation-Selection Balance a concept in evolutionary biology that describes the equilibrium between the introduction of deleterious mutations into a population through mutation and their removal through natural selection. This balance is crucial for understanding the maintenance of genetic diversity and the evolutionary dynamics of populations. Mutation-Selection Balance: In a population, mutation continuously introduces new genetic variants, including deleterious mutations. Natural selection then acts to remove these deleterious mutations. Mutation-selection balance occurs when the rate at which deleterious mutations are introduced by mutation equals the rate at which they are removed by selection. Imagine that allele ‘A’ mutates into disadvantageous allele ‘a’ at rate ‘u’. ‘u’ is usually very small, on the order of 10-8. Selection will reduce the frequency of ‘a’ to a low level, but selection is weak against uncommon recessive alleles. A mutation-selection balance will be reached where q*=equilibrium frequency of allele ‘a’=(u/s)1/2 Factors Influencing Mutation-Selection Balance Mutation Rate: The rate at which new mutations arise in a population can vary depending on factors such as the organism's biology, environmental exposures, and genetic mechanisms. Strength of Selection: The strength of natural selection against deleterious mutations depends on factors like the effect size of mutations on fitness and the population size. Stronger selection leads to more efficient removal of deleterious mutations. Population Size: Smaller populations are more susceptible to genetic drift, which can affect the maintenance of mutation-selection balance. In small populations, random fluctuations in allele frequencies can influence the fate of mutations. Genetic Variation: The existing genetic variation in a population can influence the effectiveness of selection against mutations. High genetic diversity may provide a reservoir of beneficial alleles that can offset the negative effects of deleterious mutations. Implications of Mutation-Selection Balance Genetic Diversity: contributes to the maintenance of genetic diversity within populations. It allows for the persistence of genetic variants, including rare alleles, which can be important for adaptation to changing environments. Evolutionary Dynamics: influences the rate of evolutionary change, the prevalence of genetic diseases, and the adaptive potential of species. It provides an explanation for the continued existence of alleles which, when homozygous, cause severe hereditary illnesses….most of these are in mutation-selection balance. Alleles which occur in unexpectedly high frequencies in some populations, such as sickle cell anemia, thallassemia, or cystic fibrosis, may have been subject to balancing selection in the past. The agent of selection for Sickle Cell Anemia, and for thallasemia (Mediterranean populations of humans), was probably malaria, for CF, it was most likely typhus. Alternately, it is possible that genetic drift has caused them to become more common that would be expected under this model. This may be the mechanism causing Tay Sachs disease to be unexpectedly common in certain Jewish populations. The Neutral Theory of Molecular Evolution. One of the most interesting breakthroughs in evolutionary biology in the 1960’s-1990’s, has been the development of the neutral theory of molecular evolution. It was introduced by the Japanese theoretician Motoo Kimura, in the late 1960’s. It is a theory of evolution that Darwin never could have anticipated (evolutionary biology does not begin and end with Darwin). It runs in parallel with Darwinian evolution by natural selection, though its effects are most noticeable and easiest to understand on loci for which there are no differences in fitness between alleles (thus, it is called the neutral theory). It causes change over vast spans of time, at a more-or-less constant rate, when averaged over many loci. For that reason, it can be used to develop a “molecular clock”..to tell how long it has been since two lineages have diverged.  In the 1960’s techniques of observing genetic variation in natural populations became available, and were pioneered by researchers such as Richard Lewontin. It was discovered that, in natural populations, many selectively neutral genetic polymorphisms exist. Kimura based his theory upon this. Thus, he hypothesized that much of genetic variation is actually neutral He also asserted that most evolutionary change is the result of genetic drift acting on neutral alleles. New alleles originate through the spontaneous mutation of a single nucleotide within the sequence of a gene. In single-celled organisms, or asexual, this immediately contributes a new allele to the population, and this allele is subject to drift. In sexually reproducing, multicellular organisms, the nucleotide substitution must arise within the germ line that gives rise to gametes. Most new alleles are lost due to genetic drift, but occasionally one becomes more common, and by random accident, replaces the original. The chance of this is small, but over time, it happens occasionally, at a predictable rate. In this way, neutral substitutions tend to accumulate, and genomes tend to evolve. Many of the polymorphisms we see may be “transient”-one allele is in the process of replacing another. Population Structure Most species do not exist as many populations, which are isolated from each other to some extent. Populations occasionally exchange members. Most populations are spatially structured; individuals tend to cluster in areas of suitable habitat. These local aggregations, called subpopulations, regularly exchange members. Cultural and Environmental Influences on Variation: Cultural practices and their impact on genetic variation. Environmental factors (climate, diet, disease) influencing human variation and adaptation. Human Genetic Diversity and Health: Genetic diversity in human populations. Genetic diseases and their prevalence across populations. Pharmacogenomics and personalized medicine. Ethical and Societal Implications: Ethical considerations in studying human variation and evolution. Societal impact of genetic research (identity, discrimination, privacy).