Chromosomal inheritance, Sex linked inheritance and Extra chromosomal inheritance

The chromosomal basis of inheritance

Boveri and Sutton's chromosome theory of inheritance states that genes are found at specific locations on chromosomes, and that the behavior of chromosomes during meiosis can explain Mendel’s laws of inheritance.  Thomas Hunt Morgan, who studied fruit flies, provided the first strong confirmation of the chromosome theory. Morgan discovered a mutation that affected fly eye color. He observed that the mutation was inherited differently by male and female flies. Based on the inheritance pattern, Morgan concluded that the eye color gene must be located on the X chromosome.

Waltor Sutton studied chromosomes and meiosis in grasshoppers and showed that chromosomes occur in matched pairs of maternal and paternal chromosomes which separate during meiosis and "may constitute the physical basis of the Mendelian law of heredity". Theodor Boveri studied the same things in sea urchins, in which he found that all the chromosomes had to be present for proper embryonic development to take place. In 1902 and 1903, Sutton and Boveri published independent papers proposing on chromosome theory of inheritance. This theory states that individual genes are found at specific locations on particular chromosomes, and that the behaviour of chromosomes during meiosis can explain why genes are inherited according to Mendel’s laws.

Observations that support the chromosome theory of inheritance include

·         Chromosomes, like Mendel's genes, come in matched (homologous) pairs in an organism. For both genes and chromosomes, one member of the pair comes from the mother and one from the father.

·         The members of a homologous pair separate in meiosis, so each sperm or egg receives just one member. This process is identified as segregation of alleles into gametes in Mendel's law of segregation.

·         The members of different chromosome pairs are sorted into gametes independently of one another in meiosis, just like the alleles of different genes in Mendel's law of independent assortment

Thomas Hunt Morgan, who studied fruit flies, provided the first strong confirmation of the chromosome theory. Morgan discovered a mutation that affected fly eye color. He observed that the mutation was inherited differently by male and female flies. Based on the inheritance pattern, Morgan concluded that the eye color gene must be located on the X chromosome.  Morgan chose the fruit fly, Drosophila melanogaster, for his genetic studies.

In Drosophila, normal flies have red eyes.  Red eye color is dominant. Morgan discovered a recessive mutation (allele) that caused white eyes.  When Morgan mated a red eyed female to a white eyed male, all the progeny had red eyes.   

Morgan got a surprising result when he made the reciprocal cross, mating white eyed females to red eyed males.  Instead of all red eyed progeny, he saw that all the females had red eyes and all the males had white eyes. 

This result seemed to violate Mendel’s principle of independent assortment, because two different traits (gender and eye color) seemed to be linked. This happened since the gene that caused eye color was located on (linked to) the X chromosome.  This is sex-linkage, or inheritance of genes that are on the sex chromosomes (X and Y).  Sex-linked traits show interesting inheritance patterns in part because females have two copies of each X chromosome, but males only have one.  This inheritance pattern means that a male with the recessive allele will always show the recessive trait, because he only has one copy of the allele.

Sex linked Inheritance 

In humans and other mammals, sex is determined by a pair of sex chromosomes: XY in males and XX in females.  Genes on the X chromosome are said to be X-linked. X-linked genes have distinctive inheritance patterns because they are present in different numbers in females (XX) and males (XY).  Sex-linked traits are associated with genes found on sex chromosomes. In humans, the sex chromosomes are X and Y. Because the X-chromosome is larger, X-linked traits are more common than Y-linked traits. An example of a sex-linked trait is red-green colorblindness, which is carried on the X-chromosome. Because males only have one X-chromosome, they have a higher chance of having red-green colorblindness.

X chromosome has about 800-900 protein-coding genes with a wide variety of functions, while the Y chromosome has just 60-70 protein-coding genes, about half of which are active only in the testes.

The human Y chromosome plays a key role in determining the sex of a developing embryo. This is mostly due to a gene called SRY (“sex-determining region of Y”). SRY is found on the Y chromosome and encodes a protein that turns on other genes required for male development.

XX embryos don't have SRY, so they develop as female.

XY embryos do have SRY, so they develop as male.

X-linked genes

When a gene being is present on the X chromosome, but not on the Y chromosome, it is said to be X-linked. X-linked genes have different inheritance patterns than genes on non-sex chromosomes (autosomes). That's because these genes are present in different copy numbers in males and females.

Since a female has two X chromosomes, she will have two copies of each X-linked gene. For instance, in the fruit fly Drosophila (XX females and XY males), there is a eye color gene called white that's found on the X chromosome, and a female fly will have two copies of this gene. If the gene comes in two different alleles, such as X^W (dominant, normal red eyes) and X^w (recessive, white eyes), the female fly may have any of three genotypes: X^W X^W (red eyes X^W X^w (red eyes), and X^w X^w (white eyes).

A male has different genotype possibilities than a female. Since he has only one X chromosome (paired with a Y), he will have only one copy of any X-linked genes. For instance, in the fly eye color example, the two genotypes a male can have are X^WY (red eyes) and X^wY (white eyes). Whatever allele the male fly inherits for an X-linked gene will determine his appearance, because he has no other gene copy. Males are said to be hemizygous for X-linked genes.

In humans certain conditions such as some forms of color blindness, hemophilia, and muscular dystrophy are X-linked. These diseases are much more common in men than they are in women due to their X-linked inheritance pattern.

X-inactivation (lyonization) is a process by which one of the copies of the X chromosome present in female mammals is inactivated. The inactive X chromosome is silenced by it being packaged in such a way that it has a transcriptionally inactive structure called heterochromatin known as Barr body.

Extra chromosomal inheritance - Mitochondrial and chloroplast DNA

The DNA molecules found in mitochondria and chloroplasts are small and circular and there are usually many copies of DNA in a single mitochondrion or chloroplasts.

Ways in which mitochondrial and chloroplast DNA differ from nuclear DNA

High copy number. A mitochondrion or chloroplast has multiple copies of its DNA, and a typical cell has many mitochondria (and, in the case of a plant cell, chloroplasts). As a result, cells usually have many copies – often thousands – of mitochondrial and chloroplast DNA. 

Random segregation. Mitochondria and chloroplasts (and the genes they carry) are randomly distributed to daughter cells during mitosis and meiosis. When the cell divides, the organelles that happen to be on opposite sides of the cleavage furrow or cell plate will end up in different daughter cells.

Single-parent inheritance. Non-nuclear DNA is often inherited uniparentally, meaning that offspring get DNA only from the male or the female parent, not both. In humans, for example, children get mitochondrial DNA from their mother (but not their father).  Because mitochondria are inherited from a person's mother, they provide a way to trace matrilineal ancestry (line of descent through an unbroken chain of female ancestors).

Mutations in mitochondrial DNA can lead to human genetic disorders, for example, Kearns-Sayre syndrome. Kearns-Sayre syndrome can cause symptoms such as weakness of the muscles, including those that control eyelid and eye movement, as well as degeneration of the retina and development of heart disease.  Genetic disorders caused by mitochondrial mutations are transmitted from mother to children.