Chapter 15 THE CHROMOSOMAL BASIS OF INHERITANCE
Summary of Chapter 15, BIOLOGY, 12TH ED Campbell, by J.B. Reece et al. 2014.
Mendel’s hereditary factors were an abstract concept when he proposed their existence in 1860.
Almost all cellular structures were unknown and could not provide an explanation for the transmission of these factors from one generation to the next.
Improved microscopes allowed to discover mitosis and meiosis.
· Mitosis was discovered by the German biologist Walther Flemming in 1875, in sea urchins.
· Meiosis was discovered by the Belgian zoologist Edouard van Beneben in 1890, in Ascaris eggs.
Mendel's work remained buried in libraries until 1900 when it was discovered independently by three scientists working on plant-breeding experiments.
· German Karl Correns; Austrian Erich von Tschermak; Dutchman Hugo de Vries
· Their results agreed with those of Mendel.
· Mendel's paper provided the explanation for their results.
Many biologists remained incredulous of Mendel's Law of segregation and independent assortment until evidence showed that there was a physical basis for these principles in the behavior of the chromosomes.
In 1902, Walter Sutton, Therodor Boveri and others independently noted the parallels between the behavior of the chromosomes and the behavior of Mendel's factors.
· Chromosome Theory of Inheritance.
· Genes have specific loci on chromosomes, and it is the chromosomes that undergo segregation and independent assortment.
CONCEPT I. THOMAS HUNT MORGAN, AN EXPERIMENTAL EMBRYOLOGIST AT COLUMBIA UNIVERSITY
1. MORGAN CHOICE OF EXPRIMENTAL ORGANISM
Morgan showed that Mendelian inheritance has its physical basis in the behavior of chromosomes.
Morgan selected the fruit fly Drosophila melanogaster as his research organism.
· Prolific breeders; a single mating can produce hundreds of offspring.
· Produce a new generation every two weeks.
· Easy to keep; feeds on fungi growing on ripe fruit.
· It has only four pairs of chromosomes; they can be easily identified with the light microscope.
Found a mutant male with white eyes instead of the common red eyed, called the wild type.
This white-eyed fly was called the “mutant phenotype”.
2. CORRELATING BEHAVIOR OF A GENE’S ALLELES WITH BEHAVIOR OF A CHROMOSOME PAIR.
Morgan found the correlation between a particular trait and an individual’s sex.
Morgan traced a gene to a location in a sex chromosome.
· Eye-color gene in fruit flies is found in the X sex chromosome.
Genes located in the sex chromosomes are called sex-linked genes.
Each chromosome has hundreds of thousands of genes.
Each chromosome has a linear arrangement of specific gene loci.
See Experiment shown on Fig. 15.4, page 295.
CONCEPT II. SEX-LINKED GENES EXHIBIT UNIQUE PATTERNS OF INHERITANCE.
1. THE CHROMOSOME BASIS OF SEX
Sex is commonly determined by special sex chromosomes.
Typically one sex is homogametic, that is it has a pair of similar chromosomes.
The other sex is heterogametic. It has two different sex chromosomes.
In many animals, the female is homogametic (XX) and the male heterogametic (XY).
· In some insects (e.g. grasshoppers, roaches): XX if female and X male.
· In birds some fishes and some insects: ZW is female and ZZ male.
· In most bees and ants: no sex chromosomes; diploid animals are females; haploid are males; males have no fathers, they develop from unfertilized eggs.
See Fig. 15.6 on page 296.
Chromosomes other than the sex chromosomes are called autosomes.
The Y chromosome determines male sex in mammals.
The X chromosome has many important genes unrelated to sex determination and needed in both males and females.
Genes found in the X chromosome are called sex-linked genes.
Y chromosome has several genes involved in determining the male sex.
Sex linked genes have a unique pattern of inheritance.
Some individuals have an abnormal number of sex chromosomes.
The anatomical features of gender begin to appear in the embryo at about 2 month of age.
Prior to that age, the gonads are generic and could develop into either sex according to the prevalent hormones in the embryo.
The SRY gene in the Y chromosome triggers the development of testis. There are other genes involved in the development of a normal male.
In the absence of the SRY gene, the gonads develop into ovaries.
X-linked genes have an unusual pattern of inheritance.
Males are neither homozygous nor heterozygous for X-linked genes. They are called hemizygous.
See interesting facts about the Y chromosome on: http://www.abc.net.au/science/news/stories/s884493.htm
http://www.abc.net.au/science/news/stories/s73605.htm
http://abc.net.au/science/news/stories/s63100.htm
2. INHERITANCE OF X-LINKED GENES
Some traits are carried on the sex chromosomes, X and Y.
Most traits carried are present on only the X-chromosome. The Y-chromosome is smaller, and so, very few genes are located on this chromosome.
Sex-linked disorders are more common in males than in females because the female has to have both recessive genes to show the phenotype, while the male will show whatever allele is in the X chromosome, whether dominant or recessive.
· Hemophilia, color blindness and Duchenne muscular dystrophy are sex-linked genes.
Sex-influenced genes are autosomal genes whose expression is affected by the individual sex.
Some individuals have an abnormal number of sex chromosomes:
· XXY (Klinefelter syndrome) is male with underdeveloped testes but otherwise almost normal male appearance.
· XO (Turner syndrome) has the appearance of an immature female.
· YO embryos do not survive.
See fig. 15.7 on page 297.
3. X INACTIVATION IN FEMALE MAMMALS.
Dosage competition is a mechanism that makes the two doses of in female and the single dose in the male equivalent.
In mammals, dosage competition is accomplished by the inactivation of one X chromosome.
The metabolically inactive X chromosomes is called a Barr body.
Inactivation of the X chromosome occurs randomly in each cell of the body resulting in variegation.
As a consequence, females consist of 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.
The Barr body has one active gene, the XIST gene. This gene produces multiple copies of an RNA that covers the entire chromosome.
The inactivation occurs when an methyl group, -CH3, is attached to the base cytosine of the DNA nucleotides. The process is not well understood.
All the mitotic descendants of a cell with an inactive X chromosome will carry the inactive X chromosome.
CONCEPT III. LINKAGE: LINKED GENES
Linked genes tend to be inherited together because they are located near each other on the same chromosome.
1. HOW LINKAGE AFFECTS INHERITANCE
See fig.15.9 on page 299. MORGAN’S EXPERIMENT.
2. GENETIC RECOMBINATION AND LINKAGE
A. Recombination of unlinked genes: Independent assortment of chromosomes.
Linked genes do not assort independently. During the anaphase, all these genes in the same chromosome move together to the pole.
Independent assortment of chromosomes and crossing over produce genetic recombinants.
When offspring show the same phenotype as the parents, they are called parental types.
Crossing a dominant phenotype of unknown genotype with a double recessive, therefore, of a known phenotype is called a Test Cross.
· It allows to determine if the unknown genotype is homozygous or heterozygous.
In a testcross 50% of the offspring are of the parental type and 50% are of the recombinant type.
B. Recombination of linked genes; crossing over.
When offspring have new combination of characters, they are called recombinants.
· In non-linked genes, 50% of the offspring are recombinants.
Recombination between linked genes occurs due to crossing over.
A recombination frequency of less than 50% indicates that genes are linked but that crossing over has occurred.
Exchange of genetic material between homologous chromosomes breaks linkages and establishes new linkages.
During prophase of meiosis I, paired homologous chromosomes break and corresponding points and switch fragments, creating new combinations of alleles that are then passed on to the gametes.
Some genes in long chromosomes are so far from each other that cross over between them is almost certain. These genes have a frequency over 50% and virtually the same as genes in different chromosomes.
See fig. 15.10 on page 301.
C. New Combination Of Alleles: Variation For Natural Selection
The physical behavior of chromosomes contributes to the variation in each generation.
· Crossing over occurs during the prophase of meiosis I.
· Each pair of homologous chromosomes pair up independently of other pairs during meiosis I.
These two occurrences mix the allele of both parents.
Random fertilization still increases variation eve further.
This genetic variation provides the raw material on which natural selection works.
In each generation, the alleles get reshuffled anew.
The interplay of genotype and environment will determine which genetic combination will persist over time.
3. MAPPING THE DISTACE BETWEEN GENES USING RECOMBINATION DATA
An ordered list of genetic loci along a particular chromosome is called a genetic map.
Sturtevant develop a system of finding the relative position of genes along the chromosome using recombination frequencies.
Genetic maps based on recombination frequencies are called linkage maps.
1 map unit is equivalent to a 1% recombination frequency; now it is called a centimorgan.
Geneticists use recombination data to map a chromosome's genetic loci.
The farther apart genes are in a chromosome, the more likely they are to be separated during crossing over.
If the genes are at the extremes of the chromosome, crossing over is almost a certainty and cannot be distinguished in genetic crossing from non-linked genes. Their frequency is 50%
A genetic map based on recombination frequencies is called a linkage map.
Linkage maps give the sequence of genes along the chromosome but do not give the specific location of each gene.
Cytological maps are based on detectable chromosome abnormalities or markings seen in the microscope, e.g. stained bands on the chromosome.
The entire nucleotide sequence is the ultimate physical map of a chromosome.
CONCEPT IV. ALTERATION OF CHROMOSOME NUMBER OR STRUCTURE CAUSES SOME GENETIC DISORDERS.
Physical ad chemical disturbances, as well as errors during meiosis, can damage chromosomes in major ways or alter their number in a cell.
Large chromosomal alterations often lead to spontaneous abortion.
1. ABNORMAL CHROMOSOME NUMBER
Karyotype refers to the number of chromosomes of an individual and to the photomicrograph showing the chromosomes.
Nondisjunction occurs when homologous chromosomes fail to segregate during meiosis.
Aneuploidy is the presence or absence of a single extra chromosome.
It is more common in humans than polyploidy.
· Trisomic individuals have three chromosomes of a kind.
· Monosomic individuals have a single chromosome of a kind.
· Aneuploidy is due to abnormal mitosis or meiosis when the chromosomes fail to separate in the anaphase. This is called nondisjunction.
Polyploidy is the presence of several chromosome sets.
It is common in plants but rare in animals.
· Polyploidy is lethal in humans if it occurs in all cells of the body.
· A few triploid and tetraploid individuals have been born alive and survived a few days. They were found to have a mixture of diploid and polyploid cells.
2. ALTERATIONS IN CHROMOSOME STRUCTURE.
Breakage of chromosomes can lead to four types of alterations in chromosomal structure.
Ø Deletions are loss of chromosomal material.
· A chromosome breaks and fails to rejoin.
· Most deletions are lethal.
· Cri-du-chat is due to a deletion in chromosome 5.
Ø Duplication occurs when a piece of a chromosome breaks off and becomes attached on the sister chromatid causing a duplication of genetic material in the recipient chromosome.
Ø An inversion happens when the detached piece is reattached to its chromosome but in the reverse orientation.
Ø Translocation is the attachment of part of a chromosome to a nonhomologous chromosome.
· Nonhomologous chromosomes may exchange parts, reciprocal translocation.
· It may result in the elimination or duplication of genes.
· A type of Down syndrome results from the translocation of a portion of chromosome 21 to chromosome 14. The individual has two normal chromosomes 21, one normal chromosome 14 and one abnormal chromosome 14 with a portion of chromosome 21 attached.
· The most common cause of Down syndrome is trisomy 21. Three chromosomes 21 resulting in 47 chromosomes.
· In chronic myelogenous leukemia (CML) a piece of chromosome 22 has switched places with a fragment from the tip of chromosome 9. The production of white blood cells is affected.
Deletions and duplication are especially likely to occur during meiosis.
Duplication and translocation tend to have harmful effects because essential genes may be affected.
Inversions do not cause an imbalance in the genes but the change in location may influence the phenotype due its new location and neighboring genes.
Certain cancers are apparently due to chromosomal translocations,
3. HUMAN DISORDERS DUE TO CHROMOSOMAL ALTERATIONS
· Down syndrome or trisomy 21 is the most common trisomy in humans.
· Kleinfelter syndrome, XXY, is a male with underdeveloped testes, enlarged breasts and one Barr body per cell.
· Females with XXX trisomy are normal and cannot be distinguished from XX females except by studying the karyotype. It occurs about 1 in a 1,000 births.
· Turner syndrome, XO, is an example of monosomy. The individual is a female with degenerate ovaries, slight mental retardation in some, and webbed neck.
· Autosomal monosomy has not been seeing in live births. It probably results in the death of the embryo at a very early stage.
· 17% –20% of all pregnancies recognized at 8 weeks result in spontaneous abortion (miscarriage). About half of these embryos have chromosome abnormalities. Autosomal monosomy is very rare in embryos this old.
· Cri-du-chat, cry of the cat results from a specific deletion in chromosome 5. This deletion causes severe intellectual retardation, unusual facial features and has a cry that resembles that of a cat in distress. These children die in infancy or early childhood.
· Chronic myelogenous leukemia (CML) occurs when a reciprocal translocation occurs during mitosis of cells that will become white blood cells. The exchange occurs between a large portion of chromosome 22 and a small portion of the tip chromosome 9. This results in a much shorter chromosome 22, called Philadelphia chromosome. This exchange activates a gene that causes cancer.
CONCEPT V. SOME INHERITANCE PATTERNS ARE EXCEPTIONS TO STANDARD MENDELIAN INHERITANCE
The phenotypic effect of some mammalian genes depends on whether they were inherited from the mother of from the father.
Most imprinted genes are on autosomes; they are not sex-linked.
1. GENOMIC IMPRINTING
“For most genes, we inherit two working copies -- one from mom and one from dad. But with imprinted genes, we inherit only one working copy. Depending on the gene, either the copy from mom or the copy from dad is epigenetically silenced. Silencing usually happens through the addition of methyl groups during egg or sperm formation.”
Genetic Science Learning Center. (2013, July 15) Genomic Imprinting. Retrieved November 07, 2017, from http://learn.genetics.utah.edu/content/epigenetics/imprinting/
Imprinting occurs during the formation of gametes and results in the silencing of one allele of certain genes.