CHAPTER 15 CHROMOSOMAL BASIS OF INHERITANCE

CHROMOSOMAL THEORY OF INHERITANCE - GENES HAVE SPECIFIC LOCI ON CHROMOSOMES, AND IT IS THE CHROMOSOMES THAT UNDERGO SEGREGATION AND INDEPENDENT ASSORTMENT

MORGAN THOMAS HUNT MORGAN (early 20 th century) - first to associate a specific gene with a specific chromosome Morgan chose to do his work on Drosophila melanogaster (fruit fly) - they are prolific breeders- produce hundreds of offspring in one mating, and a new generation can be bred every 2 weeks

- Morgan’s laboratory became known as “the fly room” - the fruit fly only has 4 pairs of chromosomes that are easily distinguishable with a light microscope - Morgan was probably the first person to want different varieties of the insect

After about a year, Morgan was rewarded for his work - discovered a single male with white eyes instead of the usual red WILD = most common phenotypes such as red eyes MUTANT = result from changes to the wild type alleles

SEX LINKAGE Morgan mated his white-eyed male with a red eyed female, and all F 1 offspring had red eyes - wild type is dominant - when Morgan bred these flies, he observed the classic 3:1 ratio in the F 2 flies SURPRISE? The white-eyed trait showed up only in MALES - somehow a fly’s eye color was linked to its sex

Morgan concluded that the gene that affects the white-eyed mutant is located on the X chromosome - females carry 2 copies of the gene for this character (XX), while males carry only 1(XY) - since the mutant allele is recessive, a female will only have white eyes if she receives that allele on both X chromosomes- not possible for F 2 females in Morgan’s experiments

- males need only a single copy of the mutant allele SEX-LINKED GENES- genes located on a sex chromosome

LINKED GENES Genes located on the same chromosome tend to be inherited together in genetic crosses because the chromosome is passed along as a unit - these genes are said to be LINKED GENES - the results in experiments with linked genes differ from the expected

ANOTHER EXPERIMENT BODY COLOR & WING SIZE Wild flies have gray bodies and normal wings - mutant flies have black bodies and vestigial (much smaller) wings b + = gray, b = black vg + = normal wings, vg = vestigial wings Morgan mated true breeding wild flies (b + b + vg + vg + ) with black vestigial flies (bbvgvg) to produce F 1 heterozygotes (b + bvg + vg)

- these hybrids are wild in appearance Morgan then crossed female heterozygotes with males of the double-mutant phenotype (bbvgvg) - this should have produced 4 phenotypic classes that are about equal in number: 1 gray-normal: 1 black-vestigial: 1 gray- vestigial: 1 black-normal

These were NOT the results:

Morgan reasoned that body color and wing shape are usually inherited together in specific combinations because the genes are on the same chromosomes - the few numbers of recombinant flies resulted from crossing over

GENETIC RECOMBINATION THE PRODUCTION OF OFFSPRING WITH NEW COMBINATIONS OF TRAITS INHERITED FROM 2 PARENTS - the recombination of unlinked genes is due to independent assortment of alleles (random orientation of homologous chromosomes in metaphase I of meiosis) - offspring have combinations of traits that do not match either parent

Cross a pea plant with yellow-round seeds that is heterozygous for both seed color and seed shape (YyRr) and a plant with green- wrinkled seeds (yyrr) - the gene loci for seed color and seed shape are on separate chromosomes - the alleles for these genes are assorting independently

YyRr x yyrr

- notice in your punnett square that about ½ of the offspring have phenotypes that match one of the parental phenotypes - these offspring are called PARENTAL TYPES - about ¼ have green-round seeds and ¼ have yellow-wrinkled seeds - these offspring are called RECOMBINANTS

- geneticists say there is a 50% frequency of recombination - the physical basis for this recombination is the random orientation of homologous chromosomes at metaphase I of meiosis (independent assortment)

RECOMBINATION OF LINKED GENES = CROSSING OVER - linked genes tend to move together through meiosis and fertilization - we would not expect to see recombination, but it does in fact occur - though the offspring the in cross previously mentioned did not have the 1:1:1:1 ratio, if the genes are completely linked, we should observe a 1:1:0:0 ratio

- ALL offspring should resemble the parents - most of the offspring did, but there were a few recombinants Morgan concluded that CROSSING OVER must occur: - while homologous chromosomes are paired during prophase I, nonsister chromatids may break at corresponding points and switch fragments

- this may bring together alleles in new combinations and accounts for the recombinant phenotypes in the experiment

Formula for Recombination Frequency Recombination frequency = # of recombinants x 100 Total # of offspring Total # of offspring

LINKAGE MAPS GENETIC MAP- an ordered list of the genetic loci along a particular chromosome - the farther apart 2 genes are on a chromosome, the more likely they will cross over - the greater the distance between 2 genes, the more points there are between them where crossing over can occur

LINKAGE MAP- a genetic map based on recombination frequencies - the distance between genes on a chromosome are measured in MAP UNITS - one map unit is equal to a 1% recombination frequency - sometimes genes can be so far apart on a chromosome that linkage is not observed Ex: seed color and flower color

SEX CHROMOSOMES In humans and other mammals (and fruit flies) there are 2 varieties of sex chromosomes, X and Y - A person inherits 1 chromosome from each parent - XX = female - XY = male

- in the testes and ovaries, the 2 sex chromosomes segregate during meiosis and each gamete receives one - each ovum contains an X chromosome - half the sperm cells a male produces contain an X chromosome, and half contain a Y chromosome - sex is a matter of a fifty-fifty chance

SEX-LINKED INHERITANCE Sex-linked genes follow the same pattern of inheritance that Morgan observed for the white-eyed locus - fathers pass sex-linked alleles to all of their daughters but none of their sons - mothers can pass sex-linked alleles to both sons and daughters - let’s follow a recessive, sex-linked trait

a. father with the mutant trait will transmit to all daughters but no sons b. carrier who mates with normal male will pass on mutation to half her sons and half her daughters; sons will have the disorder, daughters are carriers c. carrier who mates with male with trait, there is a 50% chance for children to have trait

SEX-LINKED DISORDERS COLORBLINDNESS - inherited as a sex-linked, recessive trait - males need only 1 copy of the recessive allele to be colorblind, while females would need two - a color-blind daughter may be born to a color-blind father whose mate is a carrier - since the sex-linked allele for colorblindness is rare, the probability that this man and woman will mate is low

DUCHENNE MUSCULAR DYSTROPHY - affects about one in every 3,500 males born in the U.S. - these people rarely live past their early 20s - sex-linked, recessive trait that causes progressive weakening of the muscles and loss of coordination - absence of a key muscle protein; the gene is at a specific locus on the X chromosome

HEMOPHILIA - sex-linked recessive trait defined by the absence of one or more of the proteins required for blood clotting - major problem is bleeding in the muscles or joints - treated with injections of the missing protein

X-INACTIVATION One X chromosome in each cell becomes almost completely inactivated during embryonic development - this inactive X in each cell of a female condenses into a compact object called a BARR BODY which lies long the inside of the nuclear envelope - most genes on the X chromosome that forms the Barr body are not expressed

The selection of which of the 2 X chromosomes that will form the Barr body occurs randomly and independently in each cell - females consist of a mosaic of two types of cells: those with the active X derived from the father and those with the active X derived from the mother

- if a female is heterozygous for a sex-linked trait, approximately half of her cells will express one allele, while the others will express the alternate allele Ex: tortoiseshell cat

Figure X inactivation and the tortoiseshell cat Tortoiseshell requires the presence of 2 different alleles, one for orange fur and one for black fur - only females can have both alleles, since only they have the 2 X chromosomes - if a female is heterozygous for the tortoiseshell gene, she is tortoiseshell

- Orange patches are formed by populations of cells in which the X chromosome with the orange allele is active - Black patches are formed in cells that have an active black allele - Calico cats also have white patches, determined by another gene

Figure 15.10x Calico cat