This article, the second in a four-part series on genes and chromosomes, explores cell division. It comes with a self-assessment enabling you to test your knowledge after reading it
Tissues and organs in the human body are not static but in a permanent state of flux, as older cells are broken down and replaced with new ones. These new cells are created by mitosis, a process of cell division whereby a diploid parent cell gives rise to two identical diploid daughter cells. By contrast, the process of meiosis, which only occurs in germinal cells, produces non-identical haploid daughter cells. Meiosis ensures genetic variability by ‘shuffling’ our ‘deck of genes’. This second article in our series on genes and chromosomes examines the two types of cell division, mitosis and meiosis.
Citation: Knight J, Andrade M (2018) Genes and chromosomes 2: cell division and genetic diversity. Nursing Times [online]; 114: 8, 40-47.
Authors: John Knight and Maria Andrade are both senior lecturers in biomedical science, College of Human Health and Science, Swansea University.
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To allow growth and repair of the human body, older senescent cells need to be removed and replaced with younger, more efficient ones. At the heart of this process is cell division, which is essential not only for maintaining the physical body but also for ensuring gene inheritance and genetic diversity.
A state of flux
It is a common misconception that, once formed, the organs of the body remain static, only gradually wearing out as we age. In reality, most of the tissues that make up the organs are in a permanent state of flux, as older cells continuously undergo apoptosis (programmed cell death) before being broken down and replaced with new ones (Elmore, 2007).
At the heart of this process of cellular replacement is cell division, which ensures a continuous supply of young ‘daughter cells’ to replace their worn-out ‘parents’. This replacement of senescent cells ensures the organs function optimally throughout our lives, although eventually the ageing process will start to take its toll.
Cells in different parts of the body are renewed at different rates; for example, epithelial cells and neutrophils divide rapidly, while hepatocytes and adipocytes divide slowly. A few cell types, such as some neurons and the eye lens cells, are thought to last a lifetime. This means different tissues and organs have different ages (Box 1).
Box 1. Replacement rates of common human cells
- Neutrophils (white blood cells): 1-5 days
- Epithelial cells of small intestine: 2-4 days
- Cervical cells: 6 days
- Alveolar cells: 8 days
- Skin epidermal cells: 10-30 days
- Erythrocytes (red blood cells): 120 days
- Hepatocytes (liver cells): 6-12 months
- Adipocytes (fat cells): 8 years
- Eye lens cells and some neurons in the central nervous system: currently thought to last a lifetime
Source: Cell Biology by the Numbers
At any one time, most cells in the body are not in an active state of division but in interphase – a stable state between phases of cell division. This is the time when cells are growing, maturing and carrying out their normal physiological functions. A typical human cell spends around 95% of its time in interphase (Cooper and Hausman, 2015).
During interphase, the nucleus of a cell has a granular appearance due to the presence of chromatin (see part 1 for more details). At this time deoxyribonucleic acid (DNA) is quite loosely arranged, with no visible chromosomes in the nuclear envelope. Just before cell division, DNA replication takes place – this ensures an identical copy of the genetic blueprint (genome) can be passed on to the future daughter cells.
The first article in this series explored the base pairing of nucleotides and described the complementary nature of the purine and pyrimidine bases (Knight and Andrade, 2018). The DNA complementary base pairing rule is:
- Adenine always pairs with thymine (A-T)
- Cytosine always pairs with guanine (C-G)
This complementary base pairing forms the basis of DNA replication during interphase.
DNA replication relies on two cellular enzymes:
- Helicase – this unwinds a small portion of the DNA double helix to make it single-stranded. This process is often described as being analogous to undoing a zip; once the DNA is single-stranded, the nucleotide bases of the parent strand are exposed;
- DNA polymerase – this fills the exposed gaps using the complementary base pairing rules. The result is two new daughter strands of DNA that are genetically identical to the parent strand.
DNA replication is often referred to as ‘semi-conservative’, as each daughter DNA double helix will have one strand derived from the original parent helix and one brand-new strand constructed from the nucleotides that have been slotted into their complementary base pairing positions by DNA polymerase (Fig 1).
The process of DNA replication is incredibly fast and random errors often occur. DNA polymerases have a ‘proofreading’ ability that allows them to double-check the new daughter strands for accuracy and correct any mistakes (Reha-Krantz, 2010); however, mistakes are sometimes overlooked, potentially resulting in genetic mutations that can lead to a variety of diseases, including malignancy.
Cell division occurs either through mitosis or meiosis. Mitosis, often referred to as the ‘normal’ cell division, is essential for the growth and repair of the human body. Most nucleated human cells have 46 chromosomes visible during cell division – this is called the diploid number (see part 1). During mitosis, the diploid number is rigorously maintained and, provided there are no DNA replication errors, all daughter cells receive a complement of DNA identical to that of their parent cells.
Mitosis occurs in four stages: prophase, metaphase, anaphase and telophase (Fig 2).
In prophase, the normal transcription and translation of DNA required for protein synthesis (see part 3) stops and the loosely arranged DNA in the nucleus, characteristic of the interphase, becomes tightly wound up by enzymes including DNA polymerase topoisomerases. This results in the DNA condensing into chromosomes (see part 1).
The appearance of chromosomes in the nucleus during prophase indicates imminent cell division. At this stage, since DNA has already been replicated, each chromosome consists of two identical sister chromatids (exact copies of the replicated chromosome) joined at a central region, the centromere.
The nuclear membrane gradually breaks down, leaving the chromosomes floating free in the cytoplasm.
Cytoplasmic organelles called centrioles produce thin contractile spindle tubules that are attached to each chromosome at its centromere, forming a scaffold. The centrioles and spindle tubules manoeuvre each chromosome into the central region (equator) of the cell.
The spindle tubules contract, thereby pulling each chromatid apart from its identical sister and towards opposite poles of the cell.
The separated chromatids are now isolated at the two opposite poles of the cell, where they form two sets of 46 chromosomes each. New nuclear membranes begin to form around each diploid set of chromosomes. The cytoplasm between the two new nuclei begins to cleave through a process called cytokinesis, which eventually results in complete separation into two new cells.
Cytokinesis ensures that each daughter cell receives a portion of cytoplasm including its essential organelles, such as mitochondria and endoplasmic reticulum. This ensures that each new cell has the intracellular components to build its own molecules and undertake cellular metabolism, allowing it to grow, mature and survive independently.
Gradually, the chromosomes in each nucleus become less distinct as they de-condense, resulting is less densely arranged DNA. The granular appearance of the nucleoplasm is restored, indicating that the cell is returning to interphase. The gene sequences encoded in the loosely arranged DNA in the nucleus can now be freely transcribed into ribonucleic acid (RNA) and eventually translated into the proteins that allow cellular growth and drive cellular metabolism (see part 3).
Control of mitosis
Mitosis is monitored via a series of ‘checkpoints’ that ensure the accurate coordination of each stage of cell division. Unfortunately, even with stringent quality control mechanisms in place, the cell division process can become dysregulated and uncontrolled, which sometimes results in malignancy (British Society for Cell Biology).
The other type of cell division, meiosis, only concerns the germinal cells in the testes and ovaries. It is essential for the formation of gametes – spermatozoa and ova – and is responsible for introducing genetic variability by ‘shuffling’ our ‘deck of genes’, ensuring that the genes carried by spermatozoa and ova are highly variable.
During meiosis, the diploid number of chromosomes (46) is halved to ensure spermatozoa and ova have the haploid number of chromosomes (23) so that, during fertilisation, when a haploid spermatozoon penetrates a haploid ovum, the diploid number is restored. It also ensures that each offspring receives roughly half their genes from the mother and half from the father. Unlike what happens in mitosis, daughter cells do not receive an identical complement of DNA from their parent cells.
Meiosis occurs in two phases, meiosis I (Fig 3) and meiosis II (Fig 4), each of which encompasses four stages (prophase, metaphase, anaphase and telophase).
Prophase I. As in mitosis, DNA replication occurs during interphase so, at the beginning of prophase I, each chromosome consists of two identical chromatids. In each of the 23 pairs of chromosomes present in our cells, one chromosome will have come from the mother and one from the father. These homologous chromosomes pair up very closely, allowing segments of adjacent sister chromatids to be swapped in a process called ‘crossing over’. During crossing over, sections of maternal and paternal chromosomes are cut, exchanged and spliced into place, with the resulting new chromosomes having different assortments of genes. This process ensures genetic variation and is largely responsible for the genetic and physical diversity in the population. After crossing over, the nuclear envelope gradually breaks down, leaving the chromosomes suspended in the cytoplasm.
Metaphase I. Spindle tubules form and attach to the chromosomes at their centromeres. The chromosomes are manoeuvred into the central region of the cell (equator).
Anaphase I. The spindle tubules contract, pulling apart each member of each homologous pair of chromosomes to opposite poles in the cell. The arrangement of maternal and paternal chromosomes during metaphase I, and their subsequent segregation during anaphase I, is completely random. This independent assortment of chromosomes ensures that spermatozoa and ova receive a good mix of maternal and paternal chromosomes.
Telophase I. The number of chromosomes at each pole of the cell has been reduced by half from 46 (diploid number) to 23 (haploid number). A new nuclear membrane gradually forms around each haploid set of chromosomes, and cytokinesis leads to cleavage of the cytoplasm. This eventually produces two new haploid daughter cells.
Each new haploid daughter cell now undergoes a second phase of cell division, meiosis II (Fig 4). The stages of meiosis II are, in most respects, identical to those of mitosis:
- Prophase II – the nuclear membrane breaks down, leaving the chromosomes suspended in the cytoplasm;
- Metaphase II – the spindle tubules form, attach to the centromere of each chromosome and manoeuvre the chromosomes into the equatorial region;
- Anaphase II – the spindle tubules contract, pulling each chromatid apart from its sister chromatid towards the opposite poles of the cell;
- Telophase II – a new nuclear envelope forms around each haploid set of chromosomes, and cytokinesis results in cleavage of the cell; this produces two new haploid daughter cells.
In men, spermatozoa are formed in the seminiferous tubules of the testes. The germinal cells in the testes (spermatogonia) give rise to diploid primary spermatocytes, which then undergo meiosis resulting in four haploid spermatozoa. Adult males produce huge numbers of spermatozoa at a rate of 80-300 million per day.
The number of ova produced by women during their reproductive years is significantly lower. The germinal cells of the ovaries (oogonia) give rise to diploid primary oocytes, which then undergo meiosis to form haploid ova (oocytes). Around two million ova are present at birth, but most of them progressively degenerate with age. This means that during her fertile years, a woman will only release, on average, around 400 viable ova (VanPutte et al, 2017).
The key function of meiosis is to create gametes that have the haploid number of 23 chromosomes. With age, the separation of homologous chromosomes that occurs during meiosis becomes less efficient, which means that extra chromosomes may be carried over into the gametes. This phenomenon is called nondisjunction.
Nondisjunction commonly results in the ova of older women having an extra copy of chromosome 21. When a sperm cell fertilises such an ovum, it will deliver its own copy of chromosome 21, resulting in trisomy 21 and a baby with Down’s syndrome (see part 1).
Although the age of the mother is commonly quoted as the major risk factor for having a baby with a chromosome disorder it is now recognised that Down’s syndrome and other examples of aneuploidy (extra or missing chromosomes) also routinely occur as a result of nondisjuction during the formation of sperm cells.
Although the age of the mother is commonly cited as the main risk factor for having a baby with Down’s syndrome or other types of aneuploidy, we now know that the age of the father is a risk factor too, as these genetic conditions also occur as a result of nondisjunction during the formation of sperm cells (US National Down Syndrome Society). Current evidence indicates that around 90% of cases of trisomy 21 result from an extra copy of chromosome 21 in the ovum, around 4% from an extra copy in the spermatozoon, and the remaining cases from errors in cell division during prenatal development (US National Institute of Child Health and Human Development).
Genes are the basic units of inheritance. The crossing over of chromosomes during meiosis and the independent assortment of chromosomes ensures that spermatozoa and ova have a random combination of genes inherited from the mother and the father. This guarantees genetic diversity. Genes ultimately encode information for constructing the proteins that build our bodies and the enzymes that control our biochemistry. Part 3 will explore the translation of DNA sequences into proteins.
- Cell division is essential for maintaining our physical body and ensuring gene inheritance and genetic diversity
- Cell division occurs either through processes of mitosis or meiosis
- In mitosis, a diploid parent cell gives rise to two identical diploid daughter cells
- In meiosis, which only occurs in the germinal cells of the ovaries and testes, a diploid parent cell produces four non-identical haploid daughter cells
- The crossing over of chromosomes during meiosis contributes to genetic diversity
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Cooper GM, Hausman RE (2015) The Cell: A Molecular Approach. Cary, NC: Sinauer Associates/Oxford University Press.
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicologic Pathology; 35: 4, 495-516.
Knight J, Andrade M (2018) Genes and chromosomes 1: basic principles of genetics. Nursing Times; 114: 7, 42-45.
Reha-Krantz LJ (2010) DNA polymerase proofreading: multiple roles maintain genome stability. Biochimica et Biophysica Acta; 1804: 5, 1049-1063.
VanPutte CL et al (2017) Seeley’s Anatomy and Physiology. New York, NY: McGraw-Hill Education.