Genetics Lesson 4 PDF

SEXUAL REPRODUCTION Not always a dichotomy. (we’ll see examples of many organisms that can have sexual or asexual reproduction in their life cycle)...

SEXUAL REPRODUCTION Not always a dichotomy. (we’ll see examples of many organisms that can have sexual or asexual reproduction in their life cycle) ASEXUAL REPRODUCTION  PARADOX OF SEXUAL REPRODUCTION Other costs for sexually reproducing organisms:. Find a mate! (energy waste, increase predation risk). Pathogens/injury during mating. Etc.. It’s all about the benefit of increased genetic diversity  evolution  adaptation to the environment sex Asex EVOLUTION INHERITANCE OF TRAITS (GENETICS) Pattern of inheritance Meiosis + fertilization  sexual reproduction  Mendelian inheritance  KEY ELEMENTS OF MENDEL’S ORIGINAL MODEL: TWO copies if you are diploid. Diploid (2n) organisms like humans, 1. HEREDITABLE TRAITS ARE DETERMINED BY HERITABLE FACTORS but remember there (GENES) also triploid, tetraploids, etc.. 2. GENES COME IN DIFFERENT VERSIONS, TWO COPIES OF THE SAME GENE (ALLELES) 3.CONCEPT OF DOMINANCE/RECESSIVITY 4. LAW OF SEGREGATION - EQUAL SEGREGATION OF GAMETES (which of the two alleles goes in a gamete is random) I’m 4n ! 5. LAW OF INDEPENDENT ASSORTMENT (genes for different traits are inherited independently of one another)  Diploid organisms have two copies of the same gene Alternative versions of a gene are called ALLELES. Usually capital Letters (e.g. A, a) are used to letters (A) are identify ALLELES associated with the dominant allele Genotype: Aa An organism inherits two versions (i.e. two alleles) of a gene, one from each parent  CONCEPT OF DOMINANCE/RECESSIVITY This (aa) is Concept of dominance/recessivity: This (AA) is homozygous no blending homozygous AA If the two alleles at a locus differ, then aa one, the dominant allele, determines the organism’s appearance; the other, the recessive allele, has no noticeable effect on the organism’s appearance. Tall is (A) and is This (Aa) is heterozygous: dominant Aa has both Short (a) is recessive alleles NOT ALWAYS THE CASE !  ‘pure’ CIAO! homozygote lines I’M A PUNNET T SQUARE AA Aa Aa A A a aa a Aa Aa Frequency in the pop: 4/4 Aa Phenotype: all tall  ‘pure’ homozygote lines Aa A a What happens if you use non ‘pure’ lines? A AA aA In other words, heterozygous Aa a Aa aa Frequency in the pop: 1/4 AA 2/4 Aa (1/2) 1/4 aa Phenotype: 3 tall, 1 short  Can you tell the genotype by looking at the phenotype ? If an organism has a dominant phenotype you can figure AA Aa out if it is heterozygote or homozygote by doing a TEST CROSS. A? AA In a test cross the organism with the dominant phenotype A ? is crossed with an organism that is homozygous recessive a Aa ?a If you have all tall F1? aa a Aa ?a A A? ? Aa If you have half tall and half short F1? a Aa ?a A? aa aa a Aa ?a  EQUAL SEGREGATION OF GAMETES (law of segregation) Equal c hances to trasmit either one or the other allele (50:50) Aa A a  PHENOTYPE Appearance of the organism, or observable trait AA Aa GENOTYPE The genetic behind (set of alleles) DOMINANCE MATTERS IN HOW THE F1 WILL LOOK BUT DOMINANCE DOES NOT MATTER IN HOW GAMETES PAIR  FF=12% Ff=15% FF ff=19% F F Female: FF Male: Ff F FF 12 FF 12 % Ff % What chances of F1 to get breast cancer? f Ff 15 Ff 15 13.5% on average % % (12+12+15+15)/4 Increased risk of 1.5%  Single gene transmission.. NOT SO SIMPLE. Sex linkage. Multiple alleles. Incomplete dominance. Codominance. Pleiotropy. Epistasis  SRY: Sex-determining Region of Y (only few functional genes on the Y chromosome)  SEX LINKAGE (X LINKAGE) Some chromosomes have different patterns of inheritance Some genes do not present 2 copies in all organisms of one species Difference between X and Y (despite they pair) Thomas Hunt Morgan  Different patterns of inheritance depending on who is mom/dad and whether the kid is male or female  DUCHENN E LOWE … X LINKED DISEASES Someone with green color blindness cannot see the difference between the pictures (simulation) X-linked recessive  When male is XY sons will exibith the phenotype of the allele on the X chromosome (in this case the one for green color blindness) XY system Males XY Female XX X0 system ZW system Female XX Females ZW Males X0 (only one sex chromosome) Males ZZ  X INACTIVATION (mammals) In the sexual chromosome there are also genes that encode for non sexual traits. So, in the homozygote sex (e.g., XX in mammals) there are some mechanisms to avoid ‘confusion’, so that both males and females will have the same copies of the X-linked genes In mammals one of the two X chromosomes gets inactivated early during embryo development (at random!) The inactive X in each cell of a female condenses into a compact object called a Barr body  Genes cannot be translated into proteins Each female is a mosaic of cells with either one or the other X chromosome inactive BUT.. Barr-body chromosomes are reactivated in the cells that give rise to eggs, resulting in every female gamete (egg) having an active X after meiosis.  X chromosomes Allele for orange fur Early embryo: Allele for black fur A few cell divisions and X chromosome In activation Two cell populations in adult cat: Active X Inactive X Active X Black fur Orange fur  Y CHROMOSOME Crossing over? Yes, but in specific regions only (pseudoautosomal) 78 genes (ca. 25 proteins) Half of those are 800 expressed genes only in testes DEGREES OF DOMINANCE: INCOMPLETE DOMINANCE Blending of the phenotypic effect of the gene  INTERMEDIATE PHENOTYPE  A closer look at the relationship between dominance and phenotype reveals an intriguing fact: For any character, the observed dominant/recessive relationship of alleles depends on the level at which we examine the phenotype. Tay-Sachs disease, an inherited disorder in humans The brain cells of a child with Tay-Sachs disease cannot metabolize certain lipids because a crucial enzyme does not work properly. As these lipids accumulate in brain cells, the child begins to suffer seizures, blindness, and degeneration of motor and mental performance and dies within a few years. Only children who inherit two copies of the Tay-Sachs allele (homozygotes) have the disease. Thus, at the organismal level, the Tay-Sachs allele qualifies as recessive. However, the activity level of the lipid-metabolizing enzyme in heterozygotes is intermediate The intermediate phenotype observed at the biochemical level is characteristic of incomplete dominance of either allele. DEGREES OF DOMINANCE: Both capital letters CODOMINANCE CO= together (e.g. feathers in chickens) the two alleles each affect the phenotype in separate, distinguishable ways. Both alleles contribute to the phenotype Heterozygous genotype = both traits appear  Single gene transmission.. NOT SO SIMPLE MULTIPLE ALLELES for one gene e.g. Human blood cells types (btw also an example of codominance) The ABO blood groups in humans, for instance, are determined by the two alleles a person has of the blood group gene; the three possible alleles are IA, IB, and i. A person’s blood group may be one of four types: A, B, AB, or O  PLEIOTROPY One genes control for multiple phenotypic trait e.g. pleiotropic alleles are responsible for the multiple symptoms of certain hereditary diseases, such as cystic fibrosis and sickle-cell disease a recessive allele of a particular gene causes both an absence of fur pigmentation (a white tiger) and a cross-eyed condition. EPISTASIS a gene at one locus alters the phenotypic expression of a gene at a second locus e.g. in Labrador retrievers coat color depends on two genes: One gene determines the pigment color (black or brown), the other gene determines whether the pigment will be deposited in the hair (dark pigment deposited, no deposition of dark pigment) This gene is epistatic to the colour, because it masks the No deposition expression of the colour means fur = yellow  It’s complicated even more... Some traits may be determined by two or more genes. The gene products may interact. Alternatively, multiple genes could independently affect a single trait  SINGLE GENE vs MULTIPLE GENE Extending Mendelian Genetics for Two or More Genes Height and other similar features are controlled by multiple (often many) genes that each make a small contribution to the overall outcome. complex traits e.g. height in humans is linked to about 400 different genes; eye colour about 16 The inheritance pattern is sometimes called polygenic inheritance POLY = MANY  QUANTITATIVE CHARACTERS usually indicates polygenic inheritance Skin pigmentation in humans is controlled by many separately Here, we simplify the story in order to understand the inherited genes—378 at latest count, many of which are concept of polygenic inheritance. involved in the production of melanin skin pigments.  SINGLE GENE vs MULTIPLE GENE Implications for inheritance Human genome has ~23,000 protein-coding genes Chromosomes are inherited Independently Mendel’s law of INDEPENDENT ASSORTMENT  MULTIPLE GENE TRANSMISSION Made easy ;) Not completely Left thumb on top: true, but dominant T (left on prentend it is… Top) Right on top: t Two independent traits which are controlled by a single gene each, those genes are on two different chromosomes. Hitchhiker’s thumb: s Straight thumb is dominant: S  mom dad TT SS x tt ss one possible gamete ea.: TS ts T and S are inherited independently mom dad Tt Ss x Tt Ss Four possible gametes ea.: TS Ts ts tS TS Ts ts tS  Left = T Straitght =S Follow the gametes Tt Ss x Tt Ss TS Ts ts tS TS Ts ts tS  Left = T Straitght =S Follow the gametes How many individuals with left and straight thumb? N= 9 dominant for both How many individuals with right and straight thumb? N= 3 recessive and dominant How many individuals with left and hitchicker thumb? N= 3 recessive and dominant How many individuals with right and hitchicker thumb? Phenotypes? N= 1 double recessive 16 possible outcomes.. 9/16 3/16 3/16 1/16 Use the probability my padawan Flip a coin: if you have two independent events, multiply the two probabilities for the joint probability ½ x ½ = 1/4  Possible outcome with Left = T only one gene in Straitght =S isolation ¼ TT, ½ Tt, ¼ tt ¼ SS, ½ Ss, ¼ ss Possible outcome with the other one gene in isolation 9 possible genotypes: TTSS TTSs TTss TTSS = ¼ x ¼ = 1/16 TtSS TtSs Ttss TTSs = ¼ x ½ = 1/8 (2/16) ttSS ttSs ttss TtSs = ½ x ½ = ¼ (4/16) Phenotypes? Sum up! 9/16 3/16 3/16 1/16 Pattern of inheritance… One gene at a time Two genes at a time, but focusing on genes that are on different chromosome  independent assortment next: two genes on the same chromosome but not so close  RE = NEW RECOMBINATION Anything that was not in the parental generation BUT THAT IS ONLY ONE TYPE! CROSSING OVER (during meiosis) INDEPENDENT ASSORTMENT (different chromosomes end up in the gametes) When you produce a gamete that has a combination of alleles that did not come from the parents: that gamete is a RECOMBINANT gamete CROSSING OVER  how do we tell if recombination is happening? A B A B Non recombinant a b gametes a b a B Recombinant gametes A b  how do we tell if recombination is happening? A B A B Non recombinant a b gametes a b a B Recombinant A B gametes A b a b WHAT IF THOSE ARE LINKED TOGETHER (if you get the A you also get the B; if you get the a you also get the b..)  NEIGHBOURING ALLELES TEND TO STAY ASSOCIATED. If you have genes close together, they tend to be inherited together.  NO MORE INDEPENDENT ASSORTMENT  Follow the gametes.. A B AB AB Ab AABb AABb A B A b aB AaBB AaBB a B In this example, if you have total linkage between a and b.. You may have only 2 type of possible F1 (AABb, AaBB). What if you don’t have total linkage? Crossing over can happen.. and the number of possible offspring increases  Follow the gametes.. A B AB AB AABb AABb Ab A B AAB AABB AB B A b aB ab AaBB AaBB a B AaBb AaBb What if you don’t have total linkage (e.g. A and B are far apart) Because of the recombinant gametes, the types of possible F1 increases: AABb, AaBB, AABB, AaBb.  RECOMBINATION DISTANCES BETWEEN GENES Genes closer to each other on a chromosome have more probability of being inherited together, and are called LINKED GENES Two close genes are separated by crossing over less often than two genes far away The frequency of crossing over between two genes (recombination frequency) reflects their distance on the chromosome By calculating genetic frequency of recombinant and of those of parental one can infer the distance between the genes GENETIC MAPS  normal fly cn vg+ cn+ vg Exercise: crossing flies that are mutant for male female one gene to flies that are mutant for another gene cinnabar eyes vestigial wings + means ok (wildtype), no + means mutant  cn vg+ cn+ vg (cn) (vg) All F1 is normal (cn + vg+) male x female Is cn dominant or recessive ? Is vg dominant or recessive ? What can be the genotype of the F1 flies? cn vg+ cn+ vg Assume cn and vg on the same chromosome All offspring (F1) looking normal cn vg+ x cn vg (normal eyes, normal wings) cn + vg cn vg Exhibit both mutations. What genotype? What are the (mom) (dad) parental and recombinant cn vg+ x cn vg offspring? cn + vg cn vg F1: Without cn vg+ cn + vg No wildtype offspring recombination cn vg cn vg No offspring like dad : 1 2  (mom) (dad) What are the parental and cn vg+ x cn vg recombinant cn + vg cn vg offspring? Without cn vg+ cn + vg F1: recombination cn vg cn vg No wildtype offspring : No offspring like dad 1 2 With cn vg cn + vg + F1: recombination: cn vg cn vg Also: (more variation in the gametes) Both mutation None (wildtype phenotype) 3 4 Offspring phenotype: Total linkage : only 1 and 2 This fractions reflect Completely unlinked : 1,2, 3 and 4 the distance between Linked but not totally so : mostly 1 & 2, some 3 &4 the genes If genes are very close together, then the fraction recombinant will be low. If the genes are very far apart, the fraction recombinant will be high. cM is not a physical measurement unit, % recombinant is called “MAP UNIT” (mu) but genetic! In Drosophila, often called centiMorgans (cM) Recombinant fraction ranges from 0% to 50% (= 0-50 cM) T. H. Morgan Gives an idea of distance between genes Developed before we had “genome sequences” and known physical distances in base-pairs In humans, average 1.3 cM ~ 1 million bases Can determine linear order of genes cn + vg 92 cn vg cn vg + 88 cn vg cn + vg + 9 cn vg recombinants 9+11 = 20/200 = 10% recombination cn vg 11 cn vg 10 cM is the distance Total flies = 200 between the two genes Extending to other genes.. You’ll get a genetic map! paired distance between: A-B 11% A-C 32 % B-C 30% RELATIVE POSITION ON A CHROMOSOME AB C  Why bother with the genetic mapping? Determine where a gene is relative to other genes Localize a gene causing a phenotype (disease gene!) The genome is not enough to understand where the gene is!. etc.. (e.g. comparison across species)  If the human genome is sequenced, we do know where the genes associated to the disease are, right? It's not easy to go from DNA sequence to disease- causing gene! GENETIC MAPPING A cross between homozygous purple-flowered and homozygous white-flowered pea plants results in offspring with purple flowers. This demonstrates. A. the blending model of genetics B.true breeding C. dominance D. the mistakes made by Mendel Imagine a pea heterozygous at the loci for flower color (Pp) and seed color (Yy). What genotypes of gametes will produce? A. two gamete types: pp and Pp B.two gamete types: pY and Py C. four gamete types: pY, py, PY, and Py D. four gamete types: Pp, Yy, pp, PP Which statement best describes the relationship between recombination frequency and the physical distance of genes on chromosomes? A. There is no relationship. All genes have random recombination frequencies. B. There is no relationship. All genes have the same, fixed recombination frequencies. C. The farther apart two genes are, the higher the recombination frequency. D. The closer together two genes are, the higher the recombination frequency. Burkitt’s lymphoma is a cancer caused by a chromosomal rearrangement in which the c-myc gene of chromosome 8 comes under the regulatory control of the IGH gene on chromosome 14. The best name for this type of rearrangement is. A. deletion B.duplication C. inversion D. translocation