Introduction to Biological Anthropology: Notes 8 Beyond Mendel: Molecular genetics, cell division, and sex Copyright Bruce Owen 2011 Mendel s model

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1 Introduction to Biological Anthropology: Notes 8 Beyond Mendel: Molecular genetics, cell division, and sex Copyright Bruce Owen 2011 Mendel s model was completely abstract. In his day, no one had ever seen a particle of inheritance nor anything that resembled Mendel s whole scheme of alleles randomly segregating into gametes, combining into offspring, and so on But now we know a lot about the physical mechanisms behind the abstract model he proposed today we will cover just enough about genetics to allow us to understand some processes that are important to how evolution works Living things are complex structures of many different chemical compounds mostly proteins the functions of living things are essentially chemical processes, largely involving proteins one of the main things that genes do is specify what proteins are produced in what places and times in order to grow an embryo into a fetus into an adult and operate all the chemical reactions that make it work throughout its life So what is a protein? proteins are a category of organic molecules a protein molecule is composed of a chain of smaller units called amino acids in the natural biological world, there are 20 different amino acids (some others can be made artificially or in non-biological processes) amino acids can form chains (proteins) in virtually any order, any combination, and any length the longest currently known in living things are about 27,000 amino acids long the sequence of amino acids in a protein is its primary structure the chain of amino acids folds and sticks to itself in a complex shape the shape is described by its secondary structure, tertiary structure, and quaternary structure, which we will not cover in detail the shape is largely determined by the sequence of amino acids: the protein s primary structure because that affects how and where the chain can bend, stick to itself, and so on a protein s primary structure and shape largely determine its chemical properties what reactions it will have with what specific other molecules Proteins have several kinds of functions some are structural proteins, which form the physical structure of the body, from cell walls, to bone, to hair, to fingernails, etc. others are motor proteins, which cause physical movement in muscles, move other molecules or structures into, out of, or within cells, and so on

2 Intro to Biological Anthro F 2011 / Owen: Molecular genetics p. 2 others are enzymes, which cause specific chemical reactions to take place the enzyme is not used up in this process; it is like a little machine that causes the reaction to happen as long as the raw materials for the reaction are present so producing an enzyme in the right circumstances is like flipping a switch to cause a particular chemical reaction to happen and other types with other functions: antibodies, signaling proteins, etc. What the genetic code codes for genes specify the primary structure of proteins: structural, motor, enzyme, etc. that is, the order of amino acids in each protein and control when, where, and how much of each protein is made also some other things, as we will see later The genetic code is carried on deoxyribonucleic acid, or DNA Not a protein itself Amazing facts for your next party, not on any test: a typical complement of human DNA in a single diploid somatic (body) cell is 46 strands of a long, narrow molecule just 20 angstroms (20 x meters) wide 38,000 strands of DNA next to each other would be about as wide as one human hair yet each strand is up to 12 cm (4 ¾ inches) long, with all 46 strands totaling about 2 meters (6 ½ feet) long! if the DNA in one cell in your body was as large around as a human hair (75 microns, 75 x 10-6 m), the 46 pieces would total about 750 kilometers long (450 miles)! at this scale, single genes would range from 2 cm (less than 1 inch) long to about 75 meters (244 feet, or 81 yards) long (500 codons x 3 bases/codon x 3.4 angstroms/base, to 2 million codons) DNA has an unusual structure that allows the molecule to encode a huge amount of information - just what is needed for a genetic code double helix structure, like a ladder twisted lengthwise (but not exactly) two long backbone strands of phosphate and sugar molecules the upright sides of the ladder connected by the rungs of the ladder, made from matched pairs of nucleotide bases there are four types of nucleotide bases: adenine, thymine, guanine, and cytosine the bases can be in any order along the backbone but the bases join to the other side only in matched pairs; adenine only to thymine, guanine only to cytosine adenine and thymine (A and T) guanine and cytosine (G and C) [note: thymine is a base in the structure of DNA; it is not the same as thiamine (or thiamin), which is vitamin B 1 ] so each side of the DNA molecule is like an extremely long sequence of seemingly random selections of the four letters (the four bases) while the other side is its complementary, inverse image

3 Intro to Biological Anthro F 2011 / Owen: Molecular genetics p. 3 DNA works as a genetic code because the sequence of the nucleotide bases determines the sequence of amino acids in a protein (the protein s primary structure) there are 20 amino acids, but only 4 bases so the code for each amino acid is a combination of 3 nucleotide bases these combinations of three bases are like 3-letter words for example, the combination Guanine, Cytosine, Thymine (GCT) codes for the amino acid alanine each of these triplets is called a codon since each codon consists of 3 bases, and there are four possibilities for each base, there are 4 x 4 x 4 = 64 possible codons 61 of these combinations signify amino acids some amino acids are specified by more than one different codon for example, GCT, GCC, GCA, and GCG all code for alanine the remaining 3 codons indicate the beginning or end of a protein So these are the two main players: proteins, which make up much of the body and regulate most of the chemical reactions in it and DNA, which carries the directions for creating the proteins In order to grow and function, organisms have to make proteins, in a process that involves these two players DNA physically controls the production of proteins in a complex process that we will cover only very superficially here Protein synthesis: the process in which DNA guides the creation of proteins that make up and operate cells and the body as a whole the process of protein synthesis, in turn, has two major stages: 1. Transcription: in which the code in the DNA is copied, or transcribed to a molecule of messenger RNA (mrna) 2. Translation: in which the mrna actually produces the protein More detail on the first stage, transciption, in which the code in a segment of DNA is copied to a new strand of messenger RNA DNA normally is inside the cell nucleus, a specialized sack of material inside the cell inside the nucleus, part of the DNA unzips into two strands, each with an exposed sequence of bases only one strand is active individual nucleotides are floating around inside the nucleus bases that are complementary to the ones exposed on the active strand stick onto the exposed bases the new nucleotides bond to each other, then peel off as a one-stranded inverse copy of the exposed portion of the DNA this single-strand copy is messenger RNA, or mrna the mrna is then edited segments called introns are clipped out, and the remaining pieces (exons) are spliced back together

4 Intro to Biological Anthro F 2011 / Owen: Molecular genetics p. 4 in many cases, a single stretch of DNA may produce multiple mrna sequences, depending on which exons are spliced back together, and in what order this seems unnecessarily complicated, but that is how it works and I have left out quite a few details already this process of producing mrna from DNA is called transcription the exposed portion of DNA typically makes many mrna molecules that carry its information the more mrna that is made, the more of the protein will ultimately be made More detail on the second stage, translation in which the protein is actually made from the code of the mrna the mrna moves out of the nucleus into the cytoplasm, the main mass of the cell, where most of the functions of the cell are carried out in the cytoplasm, the mrna encounters a structure called a ribosome where the ribosome is in contact with the mrna, a particular reaction occurs small molecules called transfer RNA (trna) can attach to the mrna with the help of the ribosome these molecules have three bases exposed on one part and another part that can bond to one specific amino acid there is one type of trna for each possible codon and each type of trna can carry only one of the 20 amino acids so the various types of trna define the translation of codons into specific amino acids in this way, only the trna with the right three complementary bases can bond to the mrna at a given point the ribosome moves along the mrna like the head of a tape player passing along a tape at each codon, it helps the appropriate complementary trna stick onto the mrna this puts an amino acid, determined by the type of trna, next to the one attached by the previous trna these bond together as the ribosome moves down the mrna the ribosome then releases the previous trna and its amino acid this forms a chain of amino acids that corresponds to the sequence of codons on the mrna a further process folds the chain up as allowed by its primary structure, and a protein has been produced there are links on the class web page to a more thorough description of the process, and to videos that cover much of this material but the level of detail in these notes is sufficient for our purposes in this class each segment of DNA that codes for a protein is a gene (actually an allele: a specific variant of a gene, like the green allele of the seed color gene) human genes range from about 500 codons long to about 2 million codons long the total human complement of DNA is about 3 billion base pairs long within which there are an estimated 30,000 to 100,000 genes each of which produces mrna that may get edited into multiple variants

5 Intro to Biological Anthro F 2011 / Owen: Molecular genetics p. 5 depending on which exons are spliced together after the introns are snipped out yet most (over 98%) of our DNA does not code for proteins about half of this is junk DNA it is never transcribed to RNA there are vast stretches that are simple repeating units others that are seemingly random garbage others that seem to be appropriate for making proteins, but are never used these are apparently turned off genes possibly ones that are damaged or no longer useful all this junk DNA apparently does nothing except take up space in the DNA sequence we will see later that having stretches of junk DNA between genes is actually useful much of the rest of this DNA does get transcribed to RNA but then is never translated into proteins so this RNA is called non-coding RNA (ncrna) some of this RNA directly performs functions ribosomes, for example, are made of this RNA, combined with proteins so we can think of DNA coding for this functional RNA in much the same way that it codes for proteins finally, some of the remainder is regulatory genes stretches of DNA that specific other molecules can bind to when they do so, they either inhibit or encourage the transcription of some other part of the DNA into RNA and thus controls the production of some protein or functional RNA Cell division: In order to grow and reproduce, cells have to divide, creating two cells where there was just one before the result of cell division is two daughter cells There are two kinds of cell division Mitosis: The common form of cell division that starts with one ordinary body cell and produces two identical body cells from it Meiosis: A special version of cell division that produces special cells (gametes: sperm and ova) that are needed for sexual reproduction First, let s consider cell division among ordinary body cells: mitosis For cells to be able to reproduce (divide), they have to be able to make a copy of their DNA for the new cell so each daughter cell will end up with a full complement of DNA this process is called DNA replication Most of the time, the DNA in a cell is floating loose in the nucleus of the cell, like spaghetti in a fishbowl (actually, more like a huge slippery hairball, but let s not go there) in this state, portions of the DNA strands are busily carrying out transcription, that is, producing mrna (and functional RNA) to make proteins to maintain and operate the cell most cells have the full allotment of DNA

6 Intro to Biological Anthro F 2011 / Owen: Molecular genetics p. 6 that is, muscle cells and liver cells both have exactly the same DNA but different parts of the DNA are active in each type of tissue so that each type of tissue has a different combination and arrangement of proteins and other components in humans, the full complement of DNA is 46 strands these strands come in pairs, so we actually have 23 pairs of strands of DNA in most cells when it is time for the cell to divide, the DNA undergoes replication as in DNA transcription, the DNA unzips at the center of each rung the nucleotide bases are exposed in the presence of the proper enzymes, the corresponding nucleotide bases are added to each one-sided strand creating two double-sided strands, each identical to the original piece of DNA Now the cell as a double complement of DNA, so when it divides, one set will go into each of the two resulting cells this temporarily doubles the number of DNA strands in the cell each of the 46 stands is accompanied by its duplicate this temporarily doubled allotment of DNA then condenses into chromosomes, which are visible with a microscope these are compact, sausage-like structures of tightly wound up DNA with some other proteins to hold it together each strand of DNA packs into a single chromosome the chromosomes vary in length and, when stained with certain dyes, have characteristic patterns of bands since in most cells, the DNA strands come in pairs, they form pairs of chromosomes with a microscope, you can see the pairs of chromosomes that match in length and banding these are called homologous pairs in humans, most cells have 23 pairs of chromosomes, or 46 chromosomes total other animal and plant species have more or fewer chromosomes the number does not seem to have much functional importance since each strand of DNA has duplicated itself, each chromosome appears to be two identically-banded sausages laying next to each other, joined at the waist, looking like a X at this stage, the cell temporarily has a double complement of chromosomes The cell is now ready to divide when body cells divide for normal growth and maintenance, they do it through a process called mitosis the doubled chromosomes line up along the middle of the cell fibers from each side of the cell connect to the centers of the chromosomes then those centers joining the duplicates break apart, and one copy of each chromosome is pulled to each side of the cell the entire cell splits between the two clumps of chromosomes producing two daughter cells, each with one complete set of chromosomes, exactly like the original cell s

7 Intro to Biological Anthro F 2011 / Owen: Molecular genetics p. 7 when cell division is over, the chromosomes unravel, the DNA sprawls out through the nucleus, and it gets back to its normal role of guiding the production of proteins except that now there are two cells with the same DNA instructions this process is called mitosis: cell division that produces daughter cells that have two of each chromosome, just like the parent cell memory aid: mitosis: produces daughter cells with Two of each chromosome this is the normal kind of division that produces almost all cells in the body Now, let s consider the special form of cell division that produces gametes (eggs/ova and sperm): meiosis sexual reproduction involves two individuals who each provide half of the genetic material for an offspring the advantage of this over just cloning one parent is that the offspring gets a new mixture of alleles, and some of these new combinations may be beneficial in order to reproduce sexually, each parent must produce special-purpose gametes with just half the normal complement of DNA that is, gametes are haploid, with just one of each of the 23 chromosomes, rather the normal two of each so that when the gametes combine to form a zygote (the first cell of the offspring), the zygote will have the normal amount of DNA that is, the zygote is diploid, like other normal body cells: it has two of each of the 23 chromosomes the zygote then divides repeatedly to create a multi-celled embryo, which develops into a fetus using the normal form of cell division discussed above (mitosis) in order for this to work, the egg and sperm must each have only half as many strands of DNA as do normal cells otherwise, when they merged, the resulting cell would have twice as many strands of DNA as either parent gametes (sperm and eggs) are created by a different kind of cell division, called meiosis meiosis produces daughter cells with half as many chromosomes as the parent cell memory aid: me1osis: produces daughter cells with 1 of each chromosome meiosis is a more complex process involving a second stage in which the daughter cells divide again but this time without doubling their DNA first resulting in four haploid daughter cells the important point is that the end product is cells with not two, but just one of each chromosome: cells that are haploid So, what is the point of sex? it creates offspring that have a mix of alleles from each parent the offspring has a different combinations of characteristics than does either parent this creates new variants for natural selection to select from sex mixes up the alleles in the offspring in two ways

8 Intro to Biological Anthro F 2011 / Owen: Molecular genetics p. 8 One: by creating a zygote that has pairs of chromosomes, one from the mother, and the other from the father so the zygote is similar in some ways to the mother, and similar in some ways to the father but is not identical to either one of them Two: the chromosomes from each parent are actually mixes of that parent s two chromosomes due to the process of crossing over during meiosis during one stage of meiosis, all of the doubled homologous pairs of chromosomes physically line up next to each other for example, the two doubled chromosome 20s lay next to each other at each point along their length, the two doubled chromosomes have loci for genes for the same proteins but the specific form of each gene (different alleles) at any given locus on the two chromosome 20s may be different because one of these doubled chromosome 20s originally came from the individual s mother, the other from the individual s father then crossing over occurs the adjacent chromosomes physically break and swap pieces for example, the tip of one of the copies of the chromosome 20 from the mother might break off, while the tip of one of the copies of the chromosome 20 from the father breaks at exactly the same point these pieces are interchanged the result is that one of the copies of the chromosome 20 from the mother now has the tip of the chromosome 20 from the father and one of the copies of the chromosome 20 from the father now has the tip of the corresponding chromosome from the mother each copy of each chromosome may experience none, one, or multiple crossings over the result of this process is to mix up even the genes on the same chromosome into new combinations this vastly increases the possible combinations of genes in the offspring With both the random combination of whole chromosomes, and crossing over that swaps batches of genes between chromosomes, the genes get almost completely randomly divided up into the gametes and a random pair of gametes combine to form a zygote the result is a new individual with an almost random combination of genes this randomizing of alleles is called independent assortment the mixing up of alleles in such a way that virtually any combination of alleles from the two parents might find its way into a given offspring what allele happens to get into the offspring for one trait is completely independent of what allele it gets for any other trait (well, not completely independent.

9 Intro to Biological Anthro F 2011 / Owen: Molecular genetics p. 9 if the loci are close together on the same chromosome the odds of crossing over cutting the chromosome right between them is low so alleles that are close together on the same chromosome tend to either both get into the gamete, or both not get into the gamete because it is rare for crossing over to separate them these alleles are said to be linked but most alleles assort independently) that is, sexual reproduction allows the offspring to have any imaginable combination of the parents genes this creates new combinations of alleles in every offspring, giving selection a nearly endless supply of new phenotypes to act upon The point of delving into all this reproduction stuff it shows the physical processes through which Mendel s abstract model actually takes place how alleles on different chromosomes get randomly mixed in the offspring how alleles on the same chromosomes still get randomly mixed in the offspring through crossing over which shows how individuals can both resemble their parents (because they have their parents alleles) and always be different from their parents and each other (because they have different combinations of those alleles than does either parent) that is, these genetic processes of sexual reproduction answer Darwin s question about where the necessary variation comes from it explains how offspring resemble their parents but how in spite of that, there is always lots of variety for selection to work on all of which creates the variation that is necessary for natural selection to work and to cause evolution understanding the basics of these processes also prepares us to see where entirely new alleles (not just new combinations of existing alleles) come from through various processes of mutation and it gives us the background to understand how natural selection really works in terms of population genetics, as we will see in the next class this complicated system of sexual reproduction with thorough mixing of alleles must itself have evolved sexual reproduction increases the variability of offspring by combining the traits of the parents in as many different ways as possible organisms that produce more variable offspring can evolve more rapidly because there is more variation for natural selection to select from populations that evolve more rapidly are more likely to survive when conditions change and are more likely to undergo speciation, creating new species so natural selection would lead to organisms with features that produce more variable offspring sexual reproduction

10 Intro to Biological Anthro F 2011 / Owen: Molecular genetics p. 10 crossing over even large amounts of junk DNA between genes because the more junk DNA there is, the more often crossing-over will cut through a section of junk, rather than a needed stretch of DNA so having lots of junk DNA should make crossing-over more successful at mixing alleles without destroying any allowing crossing over to increase the variability of offspring without causing too many errors that kill the offspring