As this karyotype displays, a diploid
human cell contains 22 pairs of homologous chromosomes and 2 sex
chromosomes. The cell has two sets of each chromosome; one of the pair
is derived from the mother and the other from the father. The maternal
and paternal chromosomes in a homologous pair have the same genes at the same locus, but possibly different alleles.
A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same loci
where they provide points along each chromosome which enable a pair of
chromosomes to align correctly with each other before separating during
meiosis. This is the basis for Mendelian inheritance which characterizes inheritance patterns of genetic material from an organism to its offspring parent developmental cell at the given time and area.
Overview
Chromosomes are linear arrangements of condensed deoxyribonucleic acid (DNA) and histone proteins, which form a complex called chromatin. Homologous chromosomes are made up of chromosome pairs of approximately the same length, centromere position, and staining pattern, for genes with the same corresponding loci.
One homologous chromosome is inherited from the organism's mother; the
other is inherited from the organism's father. After mitosis occurs
within the daughter cells, they have the correct number of genes which
are a mix of the two parents' genes. In diploid
(2n) organisms, the genome is composed of one set of each homologous
chromosome pair, as compared to tetraploid organisms which may have two
sets of each homologous chromosome pair. The alleles
on the homologous chromosomes may be different, resulting in different
phenotypes of the same genes. This mixing of maternal and paternal
traits is enhanced by crossing over during meiosis, wherein lengths of
chromosomal arms and the DNA they contain within a homologous chromosome
pair are exchanged with one another.
History
Early in the 1900s William Bateson and Reginald Punnett were studying genetic inheritance
and they noted that some combinations of alleles appeared more
frequently than others. That data and information was further explored
by Thomas Morgan. Using test cross
experiments, he revealed that, for a single parent, the alleles of
genes near to one another along the length of the chromosome move
together. Using this logic he concluded that the two genes he was
studying were located on homologous chromosomes.
Later on during the 1930s Harriet Creighton and Barbara McClintock were studying meiosis in corn cells and examining gene loci on corn chromosomes.
Creighton and McClintock discovered that the new allele combinations
present in the offspring and the event of crossing over were directly
related. This proved interchromosomal genetic recombination.
Structure
Homologous
chromosomes are chromosomes which contain the same genes in the same
order along their chromosomal arms. There are two main properties of
homologous chromosomes: the length of chromosomal arms and the placement
of the centromere.
The actual length of the arm, in accordance with the gene
locations, is critically important for proper alignment. Centromere
placement can be characterized by four main arrangements, consisting of
being either metacentric, submetacentric, acrocentric, or telocentric.
Both of these properties are the main factors for creating structural
homology between chromosomes. Therefore, when two chromosomes of the
exact structure exist, they are able to pair together to form homologous
chromosomes.
Since homologous chromosomes are not identical and do not originate from the same organism, they are different from sister chromatids. Sister chromatids result after DNA replication has occurred, and thus are identical, side-by-side duplicates of each other.
In humans
Humans have a total of 46 chromosomes, but there are only 22 pairs of homologous autosomal chromosomes. The additional 23rd pair is the sex chromosomes, X and Y.
If this pair is made up of an X and Y chromosome, then the pair of
chromosomes is not homologous because their size and gene content differ
greatly. The 22 pairs of homologous chromosomes contain the same genes
but code for different traits in their allelic forms since one was
inherited from the mother and one from the father. So humans have two homologous chromosome sets in each cell, meaning humans are diploid organisms.
Functions
Homologous
chromosomes are important in the processes of meiosis and mitosis. They
allow for the recombination and random segregation of genetic material
from the mother and father into new cells.
In meiosis
During the process of meiosis, homologous chromosomes can recombine and produce new combinations of genes in the daughter cells.
Sorting of homologous chromosomes during meiosis.
Meiosis is a round of two cell divisions that results in four haploid
daughter cells that each contain half the number of chromosomes as the
parent cell. It reduces the chromosome number in a germ cell by half by first separating the homologous chromosomes in meiosis I and then the sister chromatids in meiosis II.
The process of meiosis I is generally longer than meiosis II because it
takes more time for the chromatin to replicate and for the homologous
chromosomes to be properly oriented and segregated by the processes of
pairing and synapsis in meiosis I.
During meiosis, genetic recombination (by random segregation) and
crossing over produces daughter cells that each contain different
combinations of maternally and paternally coded genes. This recombination of genes allows for the introduction of new allele pairings and genetic variation. Genetic variation among organisms helps make a population more stable by providing a wider range of genetic traits for natural selection to act on.
Prophase I
In prophase I
of meiosis I, each chromosome is aligned with its homologous partner
and pairs completely. In prophase I, the DNA has already undergone
replication so each chromosome consists of two identical chromatids
connected by a common centromere. During the zygotene stage of prophase I, the homologous chromosomes pair up with each other. This pairing occurs by a synapsis process where the synaptonemal complex - a protein scaffold - is assembled and joins the homologous chromosomes along their lengths. Cohesin crosslinking occurs between the homologous chromosomes and helps them resist being pulled apart until anaphase. Genetic crossing-over, a type of recombination, occurs during the pachytene stage of prophase I. In addition, another type of recombination referred to as synthesis-dependent strand annealing (SDSA) frequently occurs. SDSA recombination involves information exchange between paired homologous chromatids, but not physical exchange. SDSA recombination does not cause crossing-over.
In the process of crossing-over, genes are exchanged by the
breaking and union of homologous portions of the chromosomes’ lengths. Structures called chiasmata
are the site of the exchange. Chiasmata physically link the homologous
chromosomes once crossing over occurs and throughout the process of
chromosomal segregation during meiosis. Both the non-crossover and crossover types of recombination function as processes for repairing DNA damage,
particularly double-strand breaks. At the diplotene stage of prophase I
the synaptonemal complex disassembles before which will allow the
homologous chromosomes to separate, while the sister chromatids stay
associated by their centromeres.
Metaphase I
In metaphase I of meiosis I, the pairs of homologous chromosomes, also known as bivalents or tetrads, line up in a random order along the metaphase plate.
The random orientation is another way for cells to introduce genetic
variation. Meiotic spindles emanating from opposite spindle poles attach
to each of the homologs (each pair of sister chromatids) at the kinetochore.
Anaphase I
In anaphase I of meiosis I the homologous chromosomes are pulled apart from each other. The homologs are cleaved by the enzyme separase to release the cohesin that held the homologous chromosome arms together. This allows the chiasmata to release and the homologs to move to opposite poles of the cell.
The homologous chromosomes are now randomly segregated into two
daughter cells that will undergo meiosis II to produce four haploid
daughter germ cells.
Meiosis II
After
the tetrads of homologous chromosomes are separated in meiosis I, the
sister chromatids from each pair are separated. The two haploid(because
the chromosome no. has reduced to half. Earlier two sets of chromosomes
were present, but now each set exists in two different daughter cells
that have arisen from the single diploid parent cell by meiosis I)
daughter cells resulting from meiosis I undergo another cell division in
meiosis II but without another round of chromosomal replication. The
sister chromatids in the two daughter cells are pulled apart during
anaphase II by nuclear spindle fibers, resulting in four haploid
daughter cells.
In mitosis
Homologous
chromosomes do not function the same in mitosis as they do in meiosis.
Prior to every single mitotic division a cell undergoes, the chromosomes
in the parent cell replicate themselves. The homologous chromosomes
within the cell will ordinarily not pair up and undergo genetic
recombination with each other.
Instead, the replicants, or sister chromatids, will line up along the
metaphase plate and then separate in the same way as meiosis II - by
being pulled apart at their centromeres by nuclear mitotic spindles. If any crossing over does occur between sister chromatids during mitosis, it does not produce any new recombinant genotypes.
In somatic cells
Homologous pairing in most contexts will refer to germline cells,
however also takes place in somatic cells. For example, in humans,
somatic cells have very tightly regulated homologous pairing (separated
into chromosomal territories, and pairing at specific loci under control
of developmental signalling). Other species however (notably Drosophila)
exhibit homologous pairing much more frequently. Various functions of
homologous pairing in somatic cells have been elucidated through
high-throughput screens in the early 21st century.
Problems
1.
Meiosis I 2. Meiosis II 3. Fertilization 4. Zygote Nondisjunction is
when chromosomes fail to separate normally resulting in a gain or loss
of chromosomes. In the left image the blue arrow indicates
nondisjunction taking place during meiosis II. In the right image the
green arrow is indicating nondisjunction taking place during meiosis I.
There are severe repercussions when chromosomes do not segregate properly. Faulty segregation can lead to fertility problems, embryo death, birth defects, and cancer.
Though the mechanisms for pairing and adhering homologous chromosomes
vary among organisms, proper functioning of those mechanisms is
imperative in order for the final genetic material to be sorted correctly.
Nondisjunction
Proper homologous chromosome separation in meiosis I is crucial for sister chromatid separation in meiosis II. A failure to separate properly is known as nondisjunction. There are two main types of nondisjunction that occur: trisomy and monosomy.
Trisomy is caused by the presence of one additional chromosome in the
zygote as compared to the normal number, and monosomy is characterized
by the presence of one fewer chromosome in the zygote as compared to the
normal number. If this uneven division occurs in meiosis I, then none
of the daughter cells will have proper chromosomal distribution and
severe effects can ensue, including Down’s syndrome.
Unequal division can also occur during the second meiotic division.
Nondisjunction which occurs at this stage can result in normal daughter
cells and deformed cells.
Other uses
Diagram of the general process for double-stranded break repair as well as synthesis-dependent strand annealing.
While the main function of homologous chromosomes is their use in nuclear division, they are also used in repairing double-strand breaks of DNA. These double-stranded breaks may occur in replicating DNA and are most often the result of interaction of DNA with naturally occurring damaging molecules such as reactive oxygen species. Homologous chromosomes can repair this damage by aligning themselves with chromosomes of the same genetic sequence.
Once the base pairs have been matched and oriented correctly between
the two strands, the homologous chromosomes perform a process that is
very similar to recombination, or crossing over as seen in meiosis. Part
of the intact DNA sequence overlaps with that of the damaged chromosome's sequence. Replication proteins
and complexes are then recruited to the site of damage, allowing for
repair and proper replication to occur. Through this functioning,
double-strand breaks can be repaired and DNA can function normally.
Relevant research
Current
and future research on the subject of homologous chromosome is heavily
focused on the roles of various proteins during recombination or during
DNA repair. In a recently published article by Pezza et al.
the protein known as HOP2 is responsible for both homologous chromosome
synapsis as well as double-strand break repair via homologous
recombination. The deletion of HOP2 in mice has large repercussions in
meiosis. Other current studies focus on specific proteins involved in homologous recombination as well.
There is ongoing research concerning the ability of homologous
chromosomes to repair double-strand DNA breaks. Researchers are
investigating the possibility of exploiting this capability for
regenerative medicine.
This medicine could be very prevalent in relation to cancer, as DNA
damage is thought to be contributor to carcinogenesis. Manipulating the
repair function of homologous chromosomes might allow for bettering a
cell’s damage response system. While research has not yet confirmed the
effectiveness of such treatment, it may become a useful therapy for
cancer.
