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Are Mutations Harmful?

by
Copyright =A9 1999-2003
[Text Last updated: May 23, 1999]
[Links edited: = June 20,=20 2003]

3D""

Outline

3DP=20eople often ask questions such as "Doesn't evolution depend = on=20 mutations, and aren't most mutations harmful?" and "Are there favorable=20 mutations?". In this FAQ we try to answer these questions. Briefly:

  • Mutations happen.=20
  • They happen with great regularity.=20
  • Almost all mutations are neutral.=20
  • Of the remainder, benefit/harm depends on circumstances

Biology is complicated; the jargon of the biological sciences is = formidable.=20 In this FAQ I = have tried=20 to answer common questions in simple language for the lay reader. At the = same=20 time I have tried also to provide material in greater depth for the = reader who=20 wants scientific substance.

Q: Doesn't evolution = depend on mutations=20 and aren't most mutations harmful?

A: No. Most mutations are neither harmful nor = helpful.

That's the short answer. The long answer is that mutations can be = neutral=20 (neither helpful nor harmful), strictly harmful, strictly helpful, or = (and this=20 is important) whether they are harmful or helpful depends on the = environment.=20 Most mutations are either neutral or their effect depends on the = environment.=20 Let's look at an example of a mutation which may be harmful or helpful,=20 depending upon circumstances.

English peppered moths come in two varieties, light and dark. Before = the=20 industrial revolution dark moths were very rare. During the worst years = of the=20 industrial revolution when the air was very sooty dark moths became = quite=20 common. In recent years, since the major efforts to improve air quality, = the=20 light moths are replacing the dark moths. A famous paper by H.B.D. = Kettlewell=20 proposed the following explanation for this phenomenon:

Birds eat the kind of moth they can see the best.

In England before the Industrial Revolution trees are often covered = with=20 light colored lichens. As a result light moths were favored because = they were=20 hard to see on the bark of trees whereas the dark moths were easy to = see;=20 birds ate the dark moths. During the worst years of the Industrial = Revolution=20 the air was very sooty so tree bark was dark because of soot. Dark = moths were=20 hard to see whereas the light moths were easy to see; birds ate the = light=20 moths. As a result the dark moths became common and the light moths = became=20 rare.

Despite creationist=20 criticisms, this explanation has stood the test of time. Before the=20 Industrial Revolution, a mutation which changed light moths into dark = moths was=20 an unfavorable (harmful) mutation, whereas during the dark years it was = a=20 favorable (helpful) mutation.

To see why most mutations are neither harmful nor helpful it helps to = know a=20 bit about what mutations actually are. A mutation is a change in the = genetic=20 material that controls heredity. The genetic material is contained in=20 chromosomes. Plants and animals have two copies of each chromosome = whereas=20 bacteria only have one copy. Organisms which have two copies of each = chromosomes=20 are called diploids. Those which only have one copy of each chromosome = are=20 called haploids.

Chromosomes are divided into genes, each gene being a stretch of DNA, = i.e., a=20 sequence of nucleotides (A,G,C,T for short). The location of a gene is = called a=20 locus. (The position of a nucleotide within a gene is called a site. = Don't=20 mix up locus and site.) At a given locus you may find that the DNA = sequence=20 is different from one critter to another in some small way. These are = usually=20 known as different alleles although sometimes they are confusingly = called=20 different genes. Let's call them different alleles so that we don't get=20 confused; besides that's the standard term.

If we look at populations of animals and plants we find that there = are=20 multiple alleles at 10-20% of the genes. In other words if we look at a = given=20 locus in all the members of a population about 10-20% of the time we = will find=20 more than one sequence at that locus. There can be more than two alleles = within=20 a population for a given gene locus.

Our peppered moths have a gene which controls whether the moth is = light or=20 dark.[1]=20 Since moths are diploids each moth has two copies of the gene. If both = copies of=20 a given gene are the same allele then the moth is said to be homozygous = for that=20 gene. If the two copies are different alleles then the moth is said to = be=20 heterozygous for that gene. If both alleles are the same then the moth = will be=20 light or dark, depending on which allele it has. People sometimes say = "which=20 gene it has" but that is confusing because it mixes up genes and = alleles. If a=20 moth has two different alleles (i.e. if it is heterozygous) then the hue = depends=20 on which allele is dominant. In the case of peppered moths dark is = dominant,=20 i.e., a heterozygote will be dark rather than light.

Now let's talk about how a gene might change, i.e., how one allele = might=20 change into another. There are a number of ways this might happen. We = might get=20 a point mutation, one nucleotide being replaced by another. A section = might get=20 swapped end for end. A section might be snipped out. A section might be=20 inserted. Or the entire gene might be duplicated. See the next section= for a=20 fuller description of the different kinds of mutations and their = effects.

What is the consequence when one of these things happens? Most of the = time=20 the change either has no perceptible effect at all, or it is fatal. = Coding genes=20 map into proteins using the genetic code. The genetic code is redundant = (the=20 technical term is degenerate), i.e., different triplets of nucleotides = will=20 produce the same amino acid. Because of the redundancy a point mutation = may have=20 no effect at all on the protein being coded for; these are known as = silent=20 mutations. If the sequence is altered by snipping or swapping the result = is=20 likely to be fatal because the coding sequence [the readout in terms of=20 triplets] will be messed up. However this isn't always true because = there are=20 processes that snip and insert sections of DNA into genes in a way that = doesn't=20 mess up the coding sequence.

Supose we have one of these mutations that isn't fatal but isn't = silent. What=20 happens as a result is that we get a slightly different protein. Most of = the=20 time the new protein works very much the same as the old protein - it = catalyzes=20 the same reactions. Sometimes it's functional capability changes; it now = catalyzes a different reaction. When this happens there may be another = protein=20 which also handled the original task; in this case we've added a = capability. If=20 there wasn't we lost the original capability and replaced it by a new = one.=20 Changes in enzymes (proteins that catalyze reactions) are seldom an all = or=20 nothing proposition.[3]

Gene duplication is important because it is a way to get new genes. = Once a=20 gene has been duplicated one copy can change while the other remains the = same.

Genes vary a great deal with respect to how much they can be changed = without=20 the changes harming the organism. Some genes, such as those that encode = the=20 basic metabolism and the components of the replication, transcription, = and=20 translation machinery, are hard to change without harm. We see very = little=20 variation in them from one organism to another. Such genes are said to = be=20 conserved.

"What is the net result," you may ask. Some mutations are fatal or = very bad.=20 These mutations get eliminated immediately. Some are silent and don't = count.=20 Sometimes a mutation is definitely advantageous; this is rare but it = does=20 happen. Almost all mutations which aren't silent and which aren't = eliminated=20 immediately are neither completely advantageous nor deleterious. The = mutation=20 produces a slightly different protein, and the cell and the living = organism work=20 slightly differently. Whether the mutation is helpful or harmful depends = on the=20 environment; it could be either.

If you think about it, life has to work this way - mutations (changes = in the=20 genetic material) are happening all the time. The average human being = has about=20 50-100 mutations, of which about 3 matter, i.e., they actually change a = protein.=20 If the typical mutation were deleterious life would go extinct in short = order.=20 [4]

Although most mutations are neither uniformly helpful nor harmful = they may be=20 either helpful or harmful in a particular environment. Environments are = always=20 changing, and each member of a population lives in a slightly different=20 environment from the other members. Some organisms live; some do not. = Some=20 reproduce; some do not. The alleles of those that live and reproduce get = passed=20 on. Any difference in the organism which is favorable with respect to = the=20 environment will prosper.

It is important to realize that mutations do not occur in response to = the=20 environment. They simply happen. Quite often a mutation occurs within a=20 population and then disappears because the organism had no offspring or = didn't=20 happen to pass the mutation on to its offspring; this can happen even if = the=20 mutation is beneficial. Sometimes a mutation will get established within = a=20 population by chance even though it doesn't offer an advantage; this is = known as=20 genetic drift. [8]

It is also important to realize mutations do not happen just once. = They=20 happen rarely but they keep happening over and over again within a = species. In=20 effect a mutation gets more than one bite at the apple; if it doesn't = catch on=20 the first time it appears it gets another chance.[9]

Q: Are there favorable=20 mutations?

A: There are, but it can be hard to tell.=20

For a number of reasons it is not simple to give examples of = favorable=20 mutations. First of all, as we have seen, traits [6] = may be=20 favorable or unfavorable, depending upon the environment. Secondly it is = not=20 usually known to what extent a trait is genetically fixed and to what = extent it=20 reflects a reaction to the environment. Thirdly we don't usually know = what genes=20 effect which traits. Moreover a mutation may be favorable in the sense = that it=20 permits survival in an unfavorable environment and yet be unfavorable in = a=20 better environment.

However there are a number of good examples:

  1. Antibiotic resistance in bacteria=20

    In modern times antibiotics, drugs that target specific features of = bacteria, have become very popular. Bacteria evolve very quickly so it = is not=20 surprising that they have evolved resistance to antibiotics. As a = general=20 thing this involves changing the features that antibiotics target.

    Commonly, but not always, these mutations decrease the fitness of = the=20 bacteria, i.e., in environments where there are not antibiotics = present, they=20 don't reproduce as quickly as bacteria without the mutation. This is = not=20 always true; some of these mutations do not involve any loss of = fitness. What=20 is more, there are often secondary mutations that restore fitness.

    Bacteria are easy to study. This is an advantage in evolutionary = studies=20 because we can see evolution happening in the laboratory. There is a = standard=20 experiment in which the experimenter begins with a single bacterium = and lets=20 it reproduce in a controlled environment. Since bacteria reproduce = asexually=20 all of its descendents are clones. Since reproduction is not perfect = mutations=20 happen. The experimenter can set the environment so that mutations for = a=20 particular attribute are selected. The experimenter knows both that = the=20 mutation was not present originally and, hence, when it occurred.

    In the wild it is usually impossible to determine when a mutation = occurred.=20 Usually all we know (and often we do not even know that) is the = current=20 distribution of particular traits.

    The situation with insects and pesticides is similar to that of = bacteria=20 and antibiotics. Pesticides are widely used to kill insects. In turn = the=20 insects quickly evolve in ways to become immune to the pesticides.

  2. Bacteria that eat nylon=20

    Well, no, they don't actually eat nylon; they eat short molecules = (nylon=20 oligomers) found in the waste waters of plants that produce nylon. = They=20 metabolize short nylon oligomers, breaking the nylon linkages with a = couple of=20 related enzymes. Since the bonds involved aren't found in natural = products,=20 the enzymes must have arisen since the time nylon was invented (around = the=20 1940s). It would appear this happened by new mutations in that time=20 period.

    These enzymes which break down the nylon oligomers appear to have = arisen by=20 frameshift mutation from some other gene which codes for a = functionally=20 unrelated enzyme. This adaptation has been experimentally duplicated. = In the=20 experiments, non-nylon-metabolizing strains of Pseudomonas were grown = in media=20 with nylon oligomers available as the primary food source. Within a = relatively=20 small number of generations, they developed these enzyme activities. = This=20 would appear to be an example of documented occurrence of beneficial = mutations=20 in the lab.

  3. Sickle cell resistance to malaria=20

    The sickle cell allele causes the normally round blood cell to have = a=20 sickle shape. The effect of this allele depends on whether a person = has one or=20 two copies of the allele. It is generally fatal if a person has two = copies. If=20 they have one they have sickle shaped blood cells.

    In general this is an undesirable mutation because the sickle cells = are=20 less efficient than normal cells. In areas where malaria is prevalent = it turns=20 out to be favorable because people with sickle shaped blood cells are = less=20 likely to get malaria from mosquitoes.

    This is an example where a mutation decreases the normal efficiency = of the=20 body (its fitness in one sense) but none-the-less provides a relative=20 advantage.

  4. Lactose tolerance=20

    Lactose intolerance in adult mammals has a clear evolutionary = explanation;=20 the onset of lactose intolerance makes it easy to wean the young. = Human=20 beings, however, have taken up the habit of eating milk products. This = is not=20 universal; it is something that originated in cultures that kept = cattle and=20 goats. In these cultures lactose tolerance had a strong selective = value. In=20 the modern world there is a strong correlation between lactose = tolerance and=20 having ancestors who lived in cultures that exploited milk as a = food.

    It should be understood that it was a matter of chance that the = lactose=20 tolerance mutation appeared in a group where it was advantageous. It = might=20 have been established first by genetic drift within a group which then = discovered that they could use milk. [9]

  5. Resistance to atherosclerosis=20

    Atherosclerosis is principally a disease of the modern age, one = produced by=20 modern diets and modern life-styles. There is a community in Italy = near Milan=20 (see Appendic= es=20 II and III = for=20 biological details) whose residents don't get atherosclerosis because = of a=20 fortunate mutation in one of their forebearers. This mutation is = particularly=20 interesting because the person who had the original mutation has been=20 identified.

    Note that this is a mutation that is favorable in modern times = because (a)=20 people live longer and (b) people have diets and life-styles that are = not like=20 those of our ancestors. In prehistoric times this would not have been = a=20 favorable mutation. Even today we cannot be certain that this mutation = is=20 reproductively favorable, i.e., that people with this mutation will = have more=20 than the average number of descendents. It is clear, however, that the = mutation is personally advantageous to the individuals having it.

  6. Immunity to HIV=20

    HIV infects a number of cell types including T-lymphocytes, = macrophages,=20 dendritic cells and neurons. AIDS occurs when lymphocytes, = particularly CD4+ T=20 cells are killed off, leaving the patient unable to fight off = opportunistic=20 infections. The HIV virus has to attach to molecules that are = expressed on the=20 surface of the T-cells. One of these molecules is called CD4 (or CD4=20 receptor); another is C-C chemokine receptor 5, known variously as = CCR5,=20 CCCKR5 and CKR5. Some people carry a mutant allele of the CCR5 gene = that=20 results in lack of expression of this protein on the surface of = T-cells.=20 Homozygous individuals are resistant to HIV infection and AIDS. The = frequency=20 of the mutant allele is quite high in some populations that have never = been=20 exposed to AIDS so it seems likely that there was prior selection for = this=20 allele. (See Appendix= =20 IV)

    For a description of the recent literature consult the OMIM site for CCR5.

Types of mutations = and their=20 effects

Mutations are changes in the genome (genetic constitution). There are = quite a=20 number of ways in which mutations can happen. They also differ in the = way that=20 they impact evolution.

Mutations which occur when the genome is copied during reproduction = are known=20 as vertical transfer mutations. They are called vertical transfer = mutations=20 because they are transferred from ancestor to descendent along vertical = lines of=20 descent. In the original work on population genetics it was assumed that = all=20 mutations were vertical transfer mutations.

Horizontal transfer mutations occur when DNA is moved from one = organism to=20 another. Horizontal transfer can be a major source of evolutionary = novelty. It=20 is important because new genes can be propagated much more rapidly by = horizontal=20 transfer than by vertical transfer. If evolution is depicted by the = tree,=20 vertical genetic movement is the transmission of genes down branches; = horizontal=20 genetic movement is the transmission of genes between the branches.

Intra-organism transfer mutations occur when genes or parts of genes = move=20 around within an organism.

Strictly speaking, hybrids (mating across species) are not mutants. = In many=20 groups of species, particularly among plants, genes are transferred from = to one=20 species to another via hybrids.

Types of mutations:

  1. Point mutations=20

    The most common type of copying error is the point mutation. In = this form=20 of mutation the nucleotide at a site is replaced by a different = nucleotide.=20 When people talk about mutation rates they are usually talking about = rates of=20 point mutations.

    Effects of point mutations: Point mutations in junk DNA are = common=20 but have no effect. Sometimes point mutations in regulatory regions = have no=20 effect and sometimes they alter the expression of some genes.

  2. Additions and deletions=20

    During copying a segment of DNA may be deleted or a new segment may = be=20 inserted. Typically this happens as a result of chromosome breakage or = realignment. (See below.) Additions and deletions can also be produced = by=20 certain types of horizontal transfer.

    Effects of additions and deletions: If the length of the new = or=20 deleted segment is not a multiple of three the translation will be = garbled=20 after the point at which the insertion/deletion occurred because the = frame=20 reading is now misaligned. This is known as a frameshift mutation. In = some=20 genes there are segments that may be duplicated as a block. This is = known as=20 tandem duplication.

  3. Chromosomal duplication=20

    Sometimes one or more chromosomes are duplicated during = reproduction; the=20 offspring get extra copies of those chromosomes.

    Effects of chromosomal duplication: Duplicating only one = chromosome=20 is generally disadvantageous; an example in human beings is Down's = syndrome.=20 Having multiple copies of all of the chromosomes is known as = polyploidy.=20 Polyploidy is rare in fungi and animals (although it does occur) and = is common=20 in plants. It has been estimated that 20-50% of all plant species = arise as the=20 result of polyploidy.

    Gene duplication is very common; it is important because it = provides a way=20 to evolve new capabilities while retaining the old capabilities. All=20 intermediate stages can be found in nature, from a single gene with = alternate=20 alleles to nearly identical duplicated genes with slightly different=20 functional alleles to gene families of evolutionarily related genes = with=20 different functionalities.

  4. Chromosomal breakage and realignment=20

    During reproduction a chromosome may break into two pieces or two=20 chromosomes may be joined together. A section may be moved from one = part of=20 the chromosome to another or may be flipped in orientation (inverted). = This is=20 the mechanism by which deletions, duplications and transpositions my=20 occur.

    Effects of chromosomal breakage and realignment: Quite often = these=20 types of changes do not affect the viability of the organism (the = genes are=20 still there; they're just in different places) but, in sexually = reproducing=20 species, they may make it less likely for the organism to produce = viable,=20 fertile offspring.

  5. Retroviruses=20

    Certain viruses have the ability to insert a copy of themselves = into the=20 genome of a host. The chemical that make this possible (reverse = transcriptase)=20 is widely used in genetic engineering.

    Effects of retroviruses: Usually this is a way for the virus = to get=20 the host to do the work of reproducing the virus. Sometimes, however, = the=20 inserted gene mutates and becomes a permanent part of the host = organism's=20 genome. Depending on the position of the viral DNA in the host genome, = genes=20 may be disrupted or their expression altered. When insertions occur in = the=20 germline of multicellular organisms, they can be passed on = vertically.

  6. Plasmids=20

    Plasmids are little pieces of circular DNA that are passed from = bacterium=20 to bacterium. Plasmids can be transferred across species lines.

    Effects of plasmid transfer: Plasmid transfer is an = important way of=20 spreading useful genes such as those which confer resistance to = antibiotics.=20 Plasmid transfer is an example of horizontal transfer.

  7. Bacterial DNA exchange=20

    Bacteria can exchange DNA directly. They often do this in response = to=20 environmental stress.

    Effects of bacterial DNA exchange: Exchange is often fatal = to one or=20 both of the bacteria involved. Sometimes, however, one or both of the = partners=20 acquires genes which are essential for the current environment.

  8. Higher level transfer=20

    Some parasites can pick up genetic material from one organism and = carry it=20 to the next. This has been observed in fruit flies in the wild.

    Effects of higher level transfer: When this happens novel = alleles=20 can spread much more rapidly through a species than they would for = ordinary=20 gene flow.

  9. Symbiotic transfer=20

    When two organisms exist in a close symbiotic relationship one may = "steal"=20 genes from the other. The most notable example of this are = mitochondria. In=20 most organisms with mitochondria most of the original mitochondrial = genes have=20 moved from the mitochondria to the nuclear genome.

    Effects of symbiotic transfer: A major effect is that the = symbiotic=20 relationship changes from being optional to be obligatory.

  10. Transposons=20

    Transposons are genes that can move from one place in the genome to = another.

    Effects of transposons: Depending on the position of = insertion,=20 transposons can disrupt or alter the expression of host genes. In some = species=20 most mutations due to transposon insertion. For example, in = Drosophila,=20 50-85% of mutations are due to transposon insertions.

Mutation = Studies

by Joe Boxhorn

The = material in=20 this section is by Joe Boxhorn. It goes into greater depth than the = material in=20 the rest of the FAQ. It gives a good picture of how experiments are = actually=20 run. It also gives some examples that aren't usually seen in the popular = literature.

Experimental work with bacteria, eukaryotic micro-organisms and very = small=20 animals can tell us much about the occurrence and properties of = mutations,=20 including beneficial mutations. Over the last fifty years or so = beneficial=20 mutations have been observed to occur in a number of studies.

Most of these experiments were done in a continuous culture system = called a=20 chemostat. Chemostats have been used for the last fifty years in the = study of=20 the physiology, population biology and ecology of bacteria and a variety = of=20 other small organisms. They are also used widely in the commercial = production of=20 microbe produced substances. A chemostat consists of a bottle in which = the=20 organisms grow. Growth medium (i.e. food) is continuously pumped into = the bottle=20 and waste products, residual medium and organisms flow out. The contents = of the=20 bottle are well mixed so that each critter in the chemostat has an equal = chance=20 of getting at each bit of food. Factors that affect the growth of the = organisms=20 such as temperature are controlled, sometimes quite rigourously. Several = variations of chemostats have been developed. They will be described as = they=20 become relevant.

Chemostats have several properties that make them useful for = biological=20 research. Over time, the organisms in the system reach a steady state in = which=20 organism growth equals the amount of organism flowing out of the bottle. = At this=20 steady state the concentration of organisms, measured as biomass, = remains quite=20 stable as does the concentration of residual (unused) nutrient. Numbers = can=20 change somewhat due to changes in the size of individuals. It is = important to=20 note that when the system is in steady state, the critters are growing=20 exponetially with their growth rate being the dilution rate (in flow of=20 medium/bottle volume) of the system. The average time an organism = remains in the=20 chemostat is the reciprocal of the dilution rate. These organisms are = also in a=20 steady state physiologically. The population densities of organisms = grown in=20 these continuous culture systems can be quite high. For a fast growing = bacterium=20 like E. coli densities of 3 =D7 108 per ml are readily = attainable. Similarly small eukaryotic algae such as Chlorella = vulgaris=20 can be easily be grown at densities of 3 =D7 107 per ml. = Densities on=20 the order of 105 - 106 per ml are attainable for = many=20 larger unicellular and colonial eukaryotes. The implications of this for = the=20 study of mutations are important. Assuming reasonable mutation rates and = genome=20 sizes it is virtually certain that a culture of this sort that has been = run at=20 steady state for any length of time will contain some mutant = individuals. This=20 holds even when the culture is innoculated with a strain derived from = one=20 individual in an obligately asexual species. If, for example, we assume = the=20 following characteristics for an E. coli chemostat containing = identical=20 cells:

Culture volume 500 ml
Dilution rate 1.0 per day
Genome size 5,000 genes
Population density 3 =D7 108 cells per ml
Mutation rate 10-8 mutations per gene per individual per=20 generation

We should see 7.5 =D7 106 mutant genes produced in one = day. I would=20 note that E. coli chemostats are generally run at dilution rates = far=20 faster than this. Another property of this type of system is that when = organisms=20 in a chemostat vary in their growth rates the proportion of the faster = growing=20 forms in the population tends to increase at the expense of the slower = growing=20 ones. Finally, the mathematical models describing growth of bacteria and = unicellular algae in these systems are reasonably well understood and = work=20 fairly well when compared to data (see, for example, Herbe= rt et al.=20 1956, Ku= bitschek=20 1970, Pirt=20 1975). These models do not do as well predicting the dynamics when = larger=20 organisms with more complicated life cycles are grown in chemostats.

A reinterpretation by Ku= bitschek=20 (1974) of work by Novick= and=20 Szilard (1956) suggests that the argument above was reasonable. In = this=20 study resistance to a bacterial virus was used as a marker to follow the = appearance of some mutations in a chemostat culture. Novick and Szilard = grew=20 E. coli in a chemostat at a steady-state density of about 3 =D7=20 108 cells per ml. Periodically they assayed cells sampled = from the=20 chemostat for resistance to infection by bacteriophage T5 and calculated = the=20 density of T5 resistant cells in the culture. At no time was phage T5 = present in=20 the chemostat nor had the cells in the chemostat been exposed to phage = T5. They=20 found that there was always a fraction of cells in the culture that was=20 resistant to T5. The density of resistant cells fluctuated betweeen=20 102 and 103 per ml. It followed a pattern like the = one=20 drawn below:

Skip =
graphic
  2,000 per ml
     |                                                        *
 R   |                                                       *
 e   |                                                      *
 s   |                             *                       *
 i   |                            * *                     *
 s   |                       *   *   *                   *
 t   |                      * * *     *                 *
 a   |                     *   *       *     * * * * * *
 n   |                    *             *   *
 t   |          *        *               * *
     |     *   * *      *                 *
 c   |    * * *   * *  *                  =20
 e   |   *   *     *  *
 l   |  *   =20
 l   | *=20
 s   |___________________________________________________________
    0
      0                  Generations                             700

(Note: this is = not the actual=20 graph. It shows the pattern of changes that the system went through. For = the=20 actual graph see Ku= bitschek=20 1974.) The increases and decreases reflect the occurrance of = mutations=20 within strains in the chemostat. The initial increase in the frequency = of=20 resistant cells occurs because a mutation occurs within a T5 resistant = strain=20 that makes it (and its descendents) the fastest growing cells in the = culture. As=20 long as this strain remains the fastest growing one its representation = in the=20 population will increase. Eventually different favorable mutation occurs = in a=20 cell that is sensitive to T5 that makes it (and its descendents) the = fastest=20 growing cells in the culture. This causes the frequency of T5 resistance = to=20 decline. Later a different mutation occurs in a T5 resistant strain that = makes=20 it the fastest growing strain. Its frequency increases, and so on.

It is important to note here that in this environment sensitivity and = resistance to infection by T5 is a neutral trait here. Because there is = no T5 in=20 the environment, resistance does not provide an advantage. But it = doesn't seem=20 to provide much disadvantage either. If it provided a disadvantage, the=20 resistant cells would washout of the chemostat. In this environment, it = is=20 selectively neutral. Mutations in other genes cause some cells to have a = higher=20 growth rate. It is just a matter of whether these mutations occur first = in=20 resistant or sensitive cells that determines whether the frequency of T5 = resistant cells increases or decreases. It's a hitchhiking effect - the = T5=20 resistance gene just goes along for the ride with the genes causing the=20 fluctuations.

Now in a different environment, the value of the mutation producing=20 resistance to infection by a virus might have a totally different value. = Chao et = al.=20 (1977) grew wild type E. coli B in a chemostat. Once the = vessel=20 reached steady state they innoculated it with bacteriophage T7. The = bacteria are=20 sensitive to infection by T7. Needless to say, T7 grew like mad on the = bacteria.=20 After a short time, though, a mutation attributable to a single gene = appeared in=20 a cell surface receptor site which gave tthe bacteria complete = resistance to T7.=20 This bacterial stain was designated B1. Shortly after this a mutation = occured in=20 the virus which allowed it to infect strain B1 (strain T7.1). A second = mutation=20 occurred in B1 which made it resistant to this second virus strain as = well as to=20 the original virus strain (strain B2). All five of these critters = happily=20 coexisted in the same chemostat.

Now whether these mutations were favorable or detrimental depends on = which=20 environment the critters were put in. In an environment containing T7, = E.=20 coli B1 or E. coli B2 could survive while E. coli B = suffered=20 tremendous mortality. But the mutant strains paid a cost. They were not = as fast=20 at taking up nutrient as the wild type and, consequently, could not grow = as=20 quickly. In competition experiments in phage-free environments, E. = coli B=20 outcompeted every time. So whether a mutation conferring resistance to = T7 is=20 beneficial depends on:

  1. whether there is T7 in the environment, and=20
  2. if there isn't, whether sensitive conspecifics are present. =

There has been a considerable amount of work on resistance of = bacteria to=20 bacteriophage that supports this. Some of it is reviewed in Lenski= =20 (1987).

The presence of a predator in a continuous culture system can place = strong=20 selection upon the critters being grown. When mutations appear in the = prey that=20 confer resistance to predations, they can spread through the chemostat = quite=20 rapidly -- in real time! This has been seen in many of the studies whose = results=20 are reported in the continuous culture literature.

Shika= no=20 et al. (1990) observed a major morphological change in an = unidentified gram=20 negative bacterium when it was grown in semicontinuous culture with a = predator.=20 Semicontinuous culture is a culture technique where critters are grown = in a=20 mixed flask. Periodically, a set volume of medium and organism are = removed and=20 replace by fresh medium. This type of system reaches a pseudosteady = state=20 similar to the steady state found in a chemostat. In this study, an = amotile,=20 short (1.5 micrometer) rod-shaped bacterium was grown with the ciliate = predator=20 Cyclidium. Medium transfers occurred every seventh day. After 8 to 10 = transfers=20 long bacterial cells (up to 20 micrometers) appeared in cultures which = had the=20 ciliate. These cells lacked crosswalls. They coexisted with a shorter = morph.=20 After appearance of the long form, the density of ciliates in the = experimental=20 flasks declined. Feeding experiments showed that the ciliates fed = preferentially=20 on the shorter cells.

To test whether the change in the bacterium was a genetic change, Shika= no et al.=20 (1990) examined size distributions of cell in 30 colonies derived = from an=20 experimental flask. The frequency distribution of sizes of the short = cells in=20 the the flasks were indistinguishable from those in the controls and the = parental strain. The frequency distribution of sizes for the long cells = was=20 considerably broader. The fact that daughter colonies derived from = colonies of=20 the long cells show the same distribution of cell lengths as the long = cell=20 colonies from the experimental flasks suggests that this change in = morphology=20 reflects a genetic change.

Selection for filamentous by a phagotrophic predator seems to be = common with=20 bacteria. Pe= rnthaler=20 et al. (1997) reported the appearance of a filamentous form of an=20 unidentified member of the beta-proteobacteria when the predatory = flagellate=20 Bodo saltans was added to a chemostat growing a mixed bacterial=20 assemblage. Similar filaments have been seen to appear when E. = coli is=20 grown in a chemostat with the predatory flagellate Poterioochromonas=20 malhamensis (Gillo= tt et al.=20 1993). Within about 5 days nonseptate filaments as long as 100 = micrometers=20 appeared. Many were so long that the flagellate could not completely = ingest=20 them. (Note: I have done some feeding study work with this strain. I = have=20 videotape of flagellates trying to engulf a long filament, pushing the = filament=20 through itself until the whole mess looks like a gall on a goldenrod = stem and=20 finally pushing the filament out of itself like an arrow shooting out of = a bow.)=20 E. coli has been known to produce filaments like this as a result = of=20 exposure to radiaion or chemical agents for a long time (Deeri= ng=20 1958, Curry = and=20 Greenberg 1962, Hoffm= an and=20 Frank 1963, Adler = and=20 Hardigree 1964). The mechanism appears to be a mutation in crosswall = formation (Begg = and Donachie=20 1985).

Naka= jima and=20 Kurihara (1994) produced a different favorable mutation in E. = coli.=20 They grew the bacteria in a chemostat with the predatory ciliate = Tetrahymena=20 thermophila. Within 15 days of innoculation of the ciliates, chains = of=20 normal-sized E. coli cells appeared. This morphological change = lasted=20 through several platings on agar. Again, the new form provide protection = against=20 predation.

Van den = Ende=20 (1973) introduce the ciliate predator Tetrahymena pyriformis into a=20 chemostat containing the bacterium Klebsiella aerogenes growing = in steady=20 state. During the period 140 hours to 200 hours following innoculation = with the=20 predator, the bacterium's colony morphology changed from normal mucoid=20 appearance to a glassy appearance. This reflected a loss of the = bacterium's=20 mucoid capsule. Bacteria began to adhere to the walls of the culture = vessel at=20 this time. No wall growth was seen in the controls. The morphological = change=20 seems to be an adaptation that allows the bacteria to utilize the wall = as a=20 refuge from predation. This is supported by a change van den Ende saw in = the=20 size distribution of the ciliates. At innoculation the ciliates showed a = distribution of lengths ranging from 40 - 200 micrometers. After 800 = hours in=20 the chemostat, few ciliates exceeded 60 micrometers in length. This = appears to=20 be due to starvation.

In the above cases, mutations appeared which gave resistance to = predation.=20 Mutations which confer resistance to parasites have also been seen in = studies of=20 bacteria growing in chemostats. Varon = (1979)=20 introduced the parasitic bacterium Bdellovibrio into a chemostat = with the=20 luminescent bacterium Photobacterium leiognathi growing in steady = state.=20 Within six days a new strain of the host appeared which was resistant to = attack=20 by the parasite. This mutant coexisted in the culture with a form = similar to the=20 original strain. Normally P. leiognathi grows as pairs of = rod-shaped=20 cells and forms translucent colonies. The mutant strain grows as chains = of oval=20 cells and forms opaque colonies. Plaque assays showed that the = efficiency of=20 plating of Bdellovibrio suspension on lawns of the mutant was at = least=20 107 times lower than on the original strain or on the = wild-type cells=20 from the culture. Examination of mixed suspension of parasite and host = using=20 phase-contrast microscopy showed that wild type cells were attacked = immediately=20 upon mixing by Bdellovibrio, while mutant cells remained = untouched.=20 Batch-culture studies showed that under similar culture conditions, the = mutant=20 strain has a much lower growth rate than the wild-type bacterium.

This concludes what I'm going to discuss about prokaryotes. Several=20 conclusions seem to emerge from these studies. First, given exponential = growth=20 and large population sizes, lots of mutations seem to occur in bacterial = populations. When bacteria under these conditions are placed under = strong=20 selection, by means such as the introduction of a predator or a = parasite,=20 adaptations countering the effect of the selective agent rapidly appear = and=20 spread through the population. This could not happen unless mutations = which=20 confer these benefits were appearing. This must be the case when we = consider=20 that standard practice in microbiology is to start cultures from single = colonies=20 on agar plates - colonies which represent the descendents of a single = cell.=20 Whether the mutation is beneficial depends on the environment that the = mutant is=20 in. In the presence of the selective agent (e.g. a predator), the = mutation is=20 beneficial. In a different environment the mutation may be detrimental. = A common=20 effect of mutations conferring resistance to predators and parasites = seems to be=20 a lowering of the maximum growth rate of the mutant bacteria. In at = least some=20 cases (e.g. E. coli and T phages), this results from the same = mutation=20 producing resistance and reducing the ability to take up nutrients. In = any case,=20 the appearance of beneficial mutations seems to occur in continuous = culture in a=20 number of bacterial species and is probably a general phenomenon.

It is my opinion that these conclusions also apply to eukaryotes. = I'll=20 discuss a few examples from work here in the Counter Culture Lab to = support this=20 assertion.

Chlorella vulgaris is a common unicellular green alga that is = used as=20 a "lab rat" in labs throughout the world. We've grown the same strain of = it for=20 thousands of generations on agar and in liquid culture without it losing = its=20 unicellular morphology. Dozens to hundreds of labs have done this. = Steady-state=20 unicellular C. vulgaris cultures were innoculated with the = predator=20 Ochromonas vellesiaca, a phagotrophic flagellate. Within less then 100=20 generations a multicellular form of the Chlorella became = dominanat in the=20 culture. (Boraa= s=20 1983b, Boraas= et al.=20 1998). The alga first formed globose clusters of tens to hundreds of = cells.=20 After 10-20 generations in the presence of the flagellate, eight-celled = colonies=20 predominated. These colonies retained the eight-celled morphology = indefinitely=20 in continuous culture and when plated onto agar. The basis of the change = appears=20 to be a change in the cell wall. Cell division in normal = Chlorella occurs=20 within the cell wall of the maternal cell. The cell undergoes 1-4 = divisions to=20 form 2-16 daughter cell. This is followed by a split in the mother cell = wall and=20 dispersal of the neonatal cells. In a cuture, empty mother cell walls = are=20 interspersed with whole cells at a ratio of about 1:4. Empty mother cell = walls=20 are not found in cultures of the multicellular form. The colonies are = enclosed=20 in a "membrane" which appears to be modified cell wall material.

As was seen in the bacterial cases, this mutation provided = Chlorella=20 with resistance to predation at the cost of growth rate. Neonatal = colonies are=20 barely small enough for Ochromonas to engulf. After they have grown = slightly=20 they are to big to be eaten. In the presence of the predator, the = colonial form=20 of Chlorella displaces the unicellular form and persists. When = the=20 predator is not present, the unicellular form displaces the colonial = form. This=20 makes sense as the colonial form has less surface area exposed to the=20 environment available for nutrient uptake than the unicellular form = has.

There is also evidence that mutations occur and are selected for in = animals=20 grown in chemostats and related systems. Boraa= s=20 (1983a) observed several changes the rotifer Brachionus = calyciflorus=20 when it was grown for 24 months in a chemostat. The mean adult body size = of the=20 animal declined steadily over time. Rotifers ceased production of males = and=20 resting eggs after 1-2 months in continuous culture, suggesting that the = chemostat environment selected against sexual reproduction. After 2-3 = months in=20 the sexuality could not be induced in animals removed from the culture. = They=20 appear to have lost the ability to undergo sexual reproduction.

Benne= tt=20 and Boraas (1988, 1989<= /A>) saw=20 even more striking changes in the same rotifer species when it was grown = in a=20 turbidostat. A turbidostat is a variation on the chemostat. While a = chemostat is=20 designed for constant input of medium, a turbidostat is designed to keep = the=20 organisms at a constant concentration. A turbidity sensor measures the=20 concentration of organisms in the culture. When exceeds a preset value,=20 additional medium is added. In Bennett and Boraas' study, the sensor = measured=20 the concentration of residual food (algae) in the culture (Boraas= and=20 Bennett 1988). When it dropped below a certain level, more was = added. This=20 type of culture system allows the organisms to grow at the maximum rate=20 physiologically possible in a given environment and selects for rapid = growth=20 rate. In a chemostat, the investigator chooses the growth rate that the = critters=20 grow at and the population density is a response variable, in a = turbidostat the=20 investigator chooses the population density and the critters grow as = quickly as=20 they can.

Bennett and Boraas saw the rotifers undergo several changes. The = result of=20 the changes was a fast-growing strain of the rotifer. Over 8 months in = the=20 chemostat the maximum growth rate of the rotifers increased from 0.053=20 h-1 to 0.080 h-1. This change persisted even when = the=20 animals were grown for over 100 generations in a chemostat at the slow = growth=20 rate of 0.009 h-1. There was a shift in fecundity to younger = age=20 classes in the fast-growing strain. Longevity of the fast-growing strain = was 28%=20 shorter than longevity in the parental strain. Egg development time was = shorter,=20 and egg volume was considerably smaller in the fast-growing strain. As = seen in=20 Boraa= s'=20 (1983a) study, the adults were smaller and sexuality was lost.

The rotifer example show changes in life history characters which are = under=20 genetic control. These examples suggest that the argument made for = prokaryotes=20 can be extended to eukaryotes.

Notes

[1] There are actually two different = varieties=20 of dark peppered moths, with the darkness being determined by different=20 genes.

[2] There is no note [2]. See [2] = for=20 details.

[3] Proteins are the workhorse = chemicals in the=20 cell. There are two major kinds of proteins, structural proteins and = enzymes.=20 Typically an enzyme is optimized to perform a simple chemical operation = on=20 another chemical (the substrate). However it can also perform operations = with=20 much less efficiency on other substrates. A change in an enzyme often = changes=20 its efficiency on alternate substrates; it also may change the optimal=20 conditions in which the reaction occurs, e.g. the temperature or the = pH.

Diploid organisms have two copies of each gene. When a mutation in = one copy=20 occurs the organism can have alternate alleles with different = properties. In=20 some environments organisms with copies of both alleles (they are said = to be=20 heterozygous for the gene) will have an advantage.

[4] The human genome has 3 billion = base pairs.=20 The average rate of point mutations is about 20-30 in a billion per = individual.=20 Almost all point mutations in multi-cellular organisms are strictly = neutral. In=20 human beings 90-97% of the DNA is "junk DNA" that does nothing (as best = as can=20 be determined.) One third of the changes to codons (sections of DNA that = code=20 for proteins) are silent; that is, the DNA changes, but the the amino = acid coded=20 for remains the same. Thus 93-98% of all point mutations in humans are = strictly=20 neutral.

Of the remaining 2-7% almost all of them are also neutral. A typical = protein=20 is a sequence of about 1,000 amino acids which folds up around a = reaction site=20 consisting of about 50 amino acids. Changes in the reaction site have a = strong=20 effect on the properties of the protein; changes elsewhere often do not = unless=20 they affect the folding pattern. As a result, less than 1% of the point=20 mutations are subject to selection. [7]

[5] There is no note 5 either.

[6] A trait is a physical feature of = an=20 organism. An organism's traits are determined by a combination of its = genes and=20 by its responses to its environment. The effect of genes on traits is = often very=20 indirect.

[7] Most of the numbers relating to = the size of=20 the effective genome, the number of genes, and the average size of genes = are=20 approximate and are still being refined.

A number of genomes, both bacterial and eukaryote, have been = completely=20 sequenced. Protein sizes average about 350 amino acids (1050 base = pairs).

Older estimates of the number of genes in the human genome fall in = the range=20 50-100 thousand. More recent estimates using data from the genome = project are=20 about 60-70 thousand.

Estimates of the size of the effective genome vary. Drake gives an = estimate=20 of 80,000,000 base pairs of coding DNA. The number may be as low as 3% = (Drake) or as=20 high as 10% (older estimates). The issue is complicated by the fact that = some=20 (unknown) percentage of the non-coding DNA is not junk.

Estimating mutation rates is not simple. It should be understood that = current=20 estimates are extrapolations from sampled sections in genomes. Moreover = mutation=20 rates vary for different sites. Different techniques, however, seem to=20 consistently produce estimates of 1 to 6 point non-silent mutations in = coding=20 DNA per individual in humans. The total number of point mutations per = individual=20 is much higher (Drake gives ~64; other estimates are of the same order) = but, as=20 discussed in note = 4 almost=20 all of these are either silent or are in non-coding (junk) DNA.

[8] The percentages of occurrences = of different=20 alleles in a population is always fluctuating because different = individuals have=20 different numbers of offspring. In diploid species such as ourselves = there is an=20 additional source of randomness; each offspring gets a different = combination of=20 genes from its parents. Not only are the percentages fluctuating, but = they can=20 by chance drift from one ratio to another.

This random change is what is meant by genetic drift. When a = particular=20 allele is beneficial compared to another the fluctuation will be biased; = this=20 biased movement of the changes in ratios is called natural = selection.

[9] If we use the numbers in = appendix I the=20 effective genome size (for humans) is about 80,000,000 base pairs and = the=20 average number of point mutations in the effective genome is about 4. = This works=20 out that each base pair in the effective genome will mutate about once = in every=20 20,000,000 individuals.

This means that in species with large populations such as human = beings=20 (currently) every relevant point mutation appears in the species. On the = other=20 hand, given a small group such as a hunter/gatherer tribe, a given = mutation=20 probably will not appear in the tribe.

Appendix I - = Frequency of=20 Mutations

When we speak of the frequency of mutations we have to distinguish = between=20 the mutation rate for the entire genome and the mutation rate for the = effective=20 genome (the 10% that is not junk DNA). In Genetics 148:1667-1686, April = 1998) John = W. Drake et=20 al estimate that the average human zygote has about 64 mutations, = most of=20 which occur in "junk" DNA.

From tables 4 and 5 in "Rates of Spontaneous Mutation", by JW Drake = et al,=20 Genetics 148:1667-1686 (April, 1998):

Organism Effective
genome size=20 (Ge)		 Mutations per = genome
per=20 replication
bacteriophage M13 6.4 =D7 103 0.0046
bacteriophage lambda 4.9 =D7 104 0.0038
bacteriophages T2 & T4 1.7 =D7 105 0.0040
E. coli 4.6 =D7 106 0.0025
Saccharomyces cerevisiae 1.2 =D7 107 0.0027
Neurospora crassa 4.2 =D7 107 0.0030
C. elegans 1.8 =D7 107 0.004
Drosophila 1.6 =D7 107 0.005
Mouse 8.0 =D7 107 0.014
Human 8.0 =D7 107 0.004

Note that for humans, the number of cell divisions prior to sperm = formation=20 in a male of age 30 is about 400. This works out to about 1.6 mutations = per=20 sperm cell.

In the 28 January 1999 issue of Nature, in the article = "High=20 genomic deleterious mutation rates in hominids" Walker and Kneightey = estimate that the mutation rate in the effective genome is a bit higher, = 4.2=20 mutations per individual, of which 1.6 are deleterious. See note = 7 for=20 further discussion.

Appendix II - A favorable mutation, journal = abstract

Arterioscler Thromb Vasc Biol 1998 Apr;18(4):562-567. "PAI-1 plasma = levels in=20 a general population without clinical evidence of atherosclerosis: = relation to=20 environmental and genetic determinants," by Margaglione M, Cappucci G, = d'Addedda=20 M, Colaizzo D, Giuliani N, Vecchione G, Mascolo G, Grandone E, Di Minno = G;=20 Unita' di Trombosi e Aterosclerosi, IRCCS Casa Sollievo della = Sofferenza, San=20 Giovanni Rotondo (FG), Italy.

Abstract:

Plasminogen = activator inhibitor-1 (PAI-1) plasma levels have been consistently = related to=20 a polymorphism (4G/5G) of the PAI-1 gene. The renin-angiotensin = pathway plays=20 a role in the regulation of PAI-1 plasma levels. An insertion = (I)/deletion (D)=20 polymorphism of the angiotensin-converting enzyme (ACE) gene has been = related=20 to plasma and cellular ACE levels. In 1032 employees (446 men and 586 = women;=20 22 to 66 years old) of a hospital in southern Italy, we investigated = the=20 association between PAI-1 4G/5G and the ACE I/D gene variants and = plasma PAI-1=20 antigen levels. None of the individuals enrolled had clinical evidence = of=20 atherosclerosis. In univariate analysis, PAI-1 levels were = significantly=20 higher in men (P<.001), alcohol drinkers (P<.001), smokers = (P=3D.009), and=20 homozygotes for the PAI-1 gene deletion allele (4G/4G) (P=3D.012). = Multivariate=20 analysis documented the independent effect on PAI-1 plasma levels of = body mass=20 index (P<.001), triglycerides (P<.001), sex (P<.001), PAI-1 = 4G/5G=20 polymorphism (P=3D.019), smoking habit (P=3D.041), and ACE I/D = genotype (P=3D.042).=20 Thus, in addition to the markers of insulin resistance and smoking = habit, gene=20 variants of PAI-1 and ACE account for a significant portion of the=20 between-individual variability of circulating PAI-1 antigen = concentrations in=20 a general population without clinical evidence of atherosclerosis. [Full text]

Appendix III - = A favorable=20 mutation - Journal abstract

Other Links:=20
= Apolipoprotein=20 AI Mutations and Information=20
A closer look at this mutation and the creationist reaction. =

J Biol Chem 1985 Dec 25;260(30):16321-5. "Apolipoprotein AIMilano.=20 Accelerated binding and dissociation from lipids of a human = apolipoprotein=20 variant," by Franceschini G, Vecchio G, Gianfranceschi G, Magani D, = Sirtori=20 CR.

Abstract:

The = lipid=20 binding properties of apolipoprotein (apo) AIMilano, a molecular = variant of=20 human apolipoprotein AI, characterized by the Arg173----Cys = substitution, was=20 investigated by the use of dimyristoylphosphatidylcholine liposomes. = Both the=20 variant AIMilano and normal AI are incorporated to the same extent in = stable=20 complexes isolated by gel filtration, showing similar dimensions and=20 stoichiometries. A higher affinity of apo-AIMilano for=20 dimyristoylphosphatidylcholine is suggested by the faster association = rate of=20 the variant apoprotein compared to normal AI; similarly, apo-AIMilano = is more=20 readily displaced by guanidine hydrochloride from the isolated=20 dimyristoylphosphatidylcholine- apoprotein complexes. When the = secondary=20 structure of apo-AIMilano was investigated by spectrofluoroscopy and = circular=20 dichroism, a higher fluorescence peak wavelength and a lower = alpha-helical=20 content were detected in the variant apoprotein compared to normal AI. = The=20 substitution Arg173----Cys in the AIMilano dramatically alters the = amphipathic=20 nature of the modified alpha-helical fragment of apoprotein AI. The=20 association rate with lipids is accelerated by an increased exposure = of=20 hydrophobic residues. The reduced stability of the lipid-apoprotein = particles=20 is possibly mediated by a reduction in the number of helical segments = involved=20 in lipid association. The high flexibility of the AIMilano = apolipoprotein in=20 the interaction with lipids may explain its accelerated catabolism and = the=20 possibly improved uptake capacities for tissue lipids. [Full=20 text]

Appendix IV - = Selection for=20 HIV resistance - Journal abstract

Am J Hum Genet 1998 Jun;62(6):1507-15. by JC Stephens et al.

Abstract:

The=20 CCR5-Delta32 deletion obliterates the CCR5 chemokine and the human=20 immunodeficiency virus (HIV)-1 coreceptor on lymphoid cells, leading = to strong=20 resistance against HIV-1 infection and AIDS. A genotype survey of = 4,166=20 individuals revealed a cline of CCR5-Delta32 allele frequencies of = 0%-14%=20 across Eurasia, whereas the variant is absent among native African, = American=20 Indian, and East Asian ethnic groups. Haplotype analysis of 192 = Caucasian=20 chromosomes revealed strong linkage disequilibrium between CCR5 and = two=20 microsatellite loci. By use of coalescence theory to interpret modern=20 haplotype genealogy, we estimate the origin of the = CCR5-Delta32-containing=20 ancestral haplotype to be approximately 700 years ago, with an = estimated range=20 of 275-1,875 years. The geographic cline of CCR5-Delta32 frequencies = and its=20 recent emergence are consistent with a historic strong selective event = (e.g. ,=20 an epidemic of a pathogen that, like HIV-1, utilizes CCR5), driving = its=20 frequency upward in ancestral Caucasian populations. [Full text]

References

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Bennett, W. N. and M. E. = Boraas. 1989.=20 "A demographic profile of the fastest growing metazoan: a strain of = Brachionus=20 calyciflorus (Rotifera)." Oikos. 55: 365-369.

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Acknowledgements

I wish to thank Larry Moran, Rich Daniel, Tedd Hadley, Allen Gathman, = Mike=20 Coon, Robin Goodfellow, Mike Syvanen, Joe Boxhorn, Mark Isaak, Pete = Dunkelberg,=20 and Adam Noel Harris for helpful suggestions and comments.

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