Amelogenins are a group of
protein isoforms
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...
produced by
alternative splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
or
proteolysis
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...
from the ''
AMELX
Amelogenin, X isoform is a protein that in humans is encoded by the ''AMELX'' gene. AMELX is located on the X chromosome and encodes a set of isoforms of amelogenin by alternative splicing. Amelogenin is an extracellular matrix protein involved in ...
'' gene, on the
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...
, and also the ''
AMELY
Amely was an American rock band from Orlando, Florida, United States, formed in 2008. The band comprised four members; Petie Pizarro (Vocals/Guitar), Brandon Walden (Guitar), Patrick Ridgen (Bass) and Nate Parsell (Drums). The sound of the band ...
'' gene in males, on the
Y chromosome
The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...
. They are involved in
amelogenesis
Amelogenesis is the formation of enamel on teeth and begins when the crown is forming during the advanced bell stage of tooth development after dentinogenesis forms a first layer of dentin. Dentin must be present for enamel to be formed. Amelobla ...
, the development of
enamel.
Amelogenins are type of
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
protein, which, together with
ameloblastin
Ameloblastin (abbreviated AMBN and also known as Sheathlin or Amelin) is an enamel matrix protein that in humans is encoded by the AMBN gene.
Function
Ameloblastin is a specific protein found in tooth enamel. Although less than 5% of enamel con ...
s,
enamelin
Enamelin is an enamel matrix protein (EMPs), that in humans is encoded by the ''ENAM'' gene. It is part of the non- amelogenins, which comprise 10% of the total enamel matrix proteins. It is one of the key proteins thought to be involved in ame ...
s and
tuftelin Tuftelin is an acidic phosphorylated glycoprotein found in tooth enamel. In humans, the Tuftelin protein is encoded by the ''TUFT1'' gene. It is an acidic protein that is thought to play a role in dental enamel mineralization and is implicated in ...
s, direct the mineralization of enamel to form a highly organized matrix of
rods,
interrod crystal and proteins.
Although the precise role of amelogenin(s) in regulating the
mineralization process is unknown, it is known that amelogenins are abundant during amelogenesis. Developing human enamel contains about 70% protein, 90% of which are amelogenins.
Function
Amelogenins are believed to be involved in the organizing of
enamel rod
An enamel prism, or enamel rod, is the basic unit of tooth enamel. Measuring 3-6 μm in diameter, enamel prism are tightly packed hydroxyapatite crystals structures. The hydroxyapatite crystals are hexagonal in shape, providing rigidity to the p ...
s during
tooth development
Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. For human teeth to have a healthy oral environment, all parts of the tooth must develop during appropriate stag ...
. The latest research indicates that these proteins regulate the initiation and growth of
hydroxyapatite
Hydroxyapatite, also called hydroxylapatite (HA), is a naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but it is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities. ...
crystals during the mineralization of enamel. In addition, amelogenins appear to aid in the development of
cementum
Cementum is a specialized calcified substance covering the root of a tooth. The cementum is the part of the periodontium that attaches the teeth to the alveolar bone by anchoring the periodontal ligament.Illustrated Dental Embryology, Histology, a ...
by directing cementoblasts to the tooth's root surface.
Variants
The amelogenin
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
has been most widely studied in humans, where it is a single copy gene, located on the
X and
Y chromosome
The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...
s at Xp22.1–Xp22.3 and Yp 11.2
The amelogenin gene's location on sex chromosomes has implications for variability both between the X chromosome form (
AMELX
Amelogenin, X isoform is a protein that in humans is encoded by the ''AMELX'' gene. AMELX is located on the X chromosome and encodes a set of isoforms of amelogenin by alternative splicing. Amelogenin is an extracellular matrix protein involved in ...
) and the Y chromosome form (
AMELY
Amely was an American rock band from Orlando, Florida, United States, formed in 2008. The band comprised four members; Petie Pizarro (Vocals/Guitar), Brandon Walden (Guitar), Patrick Ridgen (Bass) and Nate Parsell (Drums). The sound of the band ...
), and between alleles of AMELY among different populations. This is because AMELY exists in the
non-recombining region of chromosome Y, effectively isolating it from normal
selection pressure
Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...
s. Other sources of amelogenin variation arise from the various
isoforms
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
of AMELX obtained from alternative splicing of mRNA transcripts. Specific roles for isoforms have yet to be established. Among other organisms, amelogenin is well conserved among
eutheria
Eutheria (; from Greek , 'good, right' and , 'beast'; ) is the clade consisting of all therian mammals that are more closely related to placentals than to marsupials.
Eutherians are distinguished from noneutherians by various phenotypic tra ...
ns, and has homologs in
monotreme
Monotremes () are prototherian mammals of the order Monotremata. They are one of the three groups of living mammals, along with placentals (Eutheria), and marsupials (Metatheria). Monotremes are typified by structural differences in their brain ...
s, reptiles and amphibians.
Application in sex determination
Differences between the
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...
and
Y chromosome
The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...
versions of the amelogenin gene (AMELX and AMELY respectively) enable it to be used in sex determination of unknown human samples.
AMELX
Amelogenin, X isoform is a protein that in humans is encoded by the ''AMELX'' gene. AMELX is located on the X chromosome and encodes a set of isoforms of amelogenin by alternative splicing. Amelogenin is an extracellular matrix protein involved in ...
’s intron 1 contains a 6-base-pair deletion relative to
intron
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...
1 of
AMELY
Amely was an American rock band from Orlando, Florida, United States, formed in 2008. The band comprised four members; Petie Pizarro (Vocals/Guitar), Brandon Walden (Guitar), Patrick Ridgen (Bass) and Nate Parsell (Drums). The sound of the band ...
. This can be detected at low cost using
polymerase chain reaction
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
(PCR) of intron 1, followed by
gel electrophoresis
Gel electrophoresis is a method for separation and analysis of biomacromolecules ( DNA, RNA, proteins, etc.) and their fragments, based on their size and charge. It is used in clinical chemistry to separate proteins by charge or size (IEF ...
. Two
bands of DNA, at 555 bps and 371 bps, are resolved if both the AMELX and AMELY versions of the gene are present (i.e. the sample is from a male) or one band of DNA, at 555 bps, if the AMELX version only is present (i.e. the sample is from a female).
However because of
AMELY
Amely was an American rock band from Orlando, Florida, United States, formed in 2008. The band comprised four members; Petie Pizarro (Vocals/Guitar), Brandon Walden (Guitar), Patrick Ridgen (Bass) and Nate Parsell (Drums). The sound of the band ...
variation among individuals and populations, this method of sex determination is not 100% accurate. Mutation in regions of AMELY intron 1 commonly used as
primer annealing sites may disable PCR amplification. A 6bp
insertion to AMELY intron 1 results in an amplicon identical in length to that of AMELX. In some males AMELY may be deleted entirely. In any of these cases only one band is visualized during gel electrophoresis of PCR products, causing misidentification of the sample as female.
The misidentification rate may vary among populations, but in general appears to be low. In one study in Spain, the amelogenin sex determination test using AMELX (977bps) and AMELY (790bps) bands was performed for 1224 individuals of known gender with a 99.84% (1222/1224) accuracy rate.
Another study in India, however, found 5 of its 270 men studied (1.85%) possessed an AMELY deletion, terming them “deleted-amelogenin males” (DAMs). In response the authors suggested that while the amelogenin sex test may be accurate in general, other Y chromosome markers such as
SRY, STR, or 50f2 can be used for less ambiguous gender identification.
Clinical significance
Mutations in AMELX can cause
amelogenesis imperfecta
Amelogenesis imperfecta (AI) is a congenital disorder which presents with a rare abnormal formation of the enamel or external layer of the crown of teeth, unrelated to any systemic or generalized conditions. Enamel is composed mostly of mineral, ...
, a disorder of tooth enamel development.
References
{{reflist
Human proteins
Teeth
Genetics