https://en.wikipedia.org/wiki/Synapsis Synapsis during Meiosis. The circled area is the part where synapsis occurs, where the two chromatids meet before crossing over
Synapsis or Syzygy is the pairing of two chromosomes that occurs during meiosis. It allows matching-up of homologous pairs prior to their segregation, and possible chromosomal crossover between them. Synapsis takes place during prophase I of meiosis.
When homologous chromosomes synapse, their ends are first attached to
the nuclear envelope. These end-membrane complexes then migrate,
assisted by the extranuclear cytoskeleton,
until matching ends have been paired. Then the intervening regions of
the chromosome are brought together, and may be connected by a
protein-DNA complex called the synaptonemal complex. During synapsis, autosomes are held together by the synaptonemal complex along their whole length, whereas for sex chromosomes, this only takes place at one end of each chromosome.
This is not to be confused with mitosis. Mitosis also has prophase, but does not ordinarily do pairing of two homologous chromosomes.
When the non-sister chromatids intertwine, segments of chromatids
with similar sequence may break apart and be exchanged in a process
known as genetic recombination or "crossing-over". This exchange produces a chiasma,
a region that is shaped like an X, where the two chromosomes are
physically joined. At least one chiasma per chromosome often appears to
be necessary to stabilise bivalents along the metaphase
plate during separation. The crossover of genetic material also
provides a possible defences against 'chromosome killer' mechanisms, by
removing the distinction between 'self' and 'non-self' through which
such a mechanism could operate. A further consequence of recombinant
synapsis is to increase genetic variability
within the offspring. Repeated recombination also has the general
effect of allowing genes to move independently of each other through the
generations, allowing for the independent concentration of beneficial
genes and the purging of the detrimental.
Following synapsis, a type of recombination referred to as
synthesis dependent strand annealing (SDSA) occurs frequently. SDSA
recombination involves information exchange between paired non-sister
homologous chromatids, but not physical exchange. SDSA recombination
does not cause crossing-over. Both the non-crossover and crossover
types of recombination function as processes for repairing DNA damage,
particularly double-strand breaks (see Genetic recombination).
The central function of synapsis is therefore the identification
of homologues by pairing, an essential step for a successful meiosis.
The processes of DNA repair and chiasma formation that take place
following synapsis have consequences at many levels, from cellular
survival through to impacts upon evolution itself.
Chromosome silencing
In mammals, surveillance mechanisms remove meiotic cells in which synapsis is defective. One such surveillance mechanism is meiotic silencing that involves the transcriptional silencing of genes on asynapsed chromosomes. Any chromosome region, either in males or females, that is asynapsed is subject to meiotic silencing. ATR, BRCA1 and gammaH2AX localize to unsynapsed chromosomes at the pachytene stage of meiosis in human oocytes and this may lead to chromosome silencing. The DNA damage response protein TOPBP1 has also been identified as a crucial factor in meiotic sex chromosome silencing. DNA double-strand breaks appear to be initiation sites for meiotic silencing.
Recombination
In female Drosophila melanogaster fruit flies, meiotic chromosome synapsis occurs in the absence of recombination. Thus synapsis in Drosophila
is independent of meiotic recombination, consistent with the view that
synapsis is a precondition required for the initiation of meiotic
recombination. Meiotic recombination is also unnecessary for homologous chromosome synapsis in the nematode.
A
model of meiotic recombination, initiated by a double-strand break or
gap, followed by pairing with an homologous chromosome and strand
invasion to initiate the recombinational repair process. Repair of the
gap can lead to crossover (CO) or non-crossover (NCO) of the flanking
regions. CO recombination is thought to occur by the Double Holliday
Junction (DHJ) model, illustrated on the right. NCO recombinants are
thought to occur primarily by the Synthesis Dependent Strand Annealing
(SDSA) model, illustrated on the left. Most recombination events appear
to be the SDSA type.
Genetic recombination (also known as genetic reshuffling) is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles
whose loci are on different but homologous chromosomes (random
orientation of pairs of homologous chromosomes in meiosis I); & (2) intrachromosomal recombination, occurring through crossing over.
During meiosis in eukaryotes, genetic recombination involves the pairing of homologous chromosomes.
This may be followed by information transfer between the chromosomes.
The information transfer may occur without physical exchange (a section
of genetic material is copied from one chromosome to another, without
the donating chromosome being changed) (see SDSA – Synthesis Dependent
Strand Annealing pathway in Figure); or by the breaking and rejoining of
DNA strands, which forms new molecules of DNA (see DHJ pathway in Figure).
Recombination may also occur during mitosis
in eukaryotes where it ordinarily involves the two sister chromosomes
formed after chromosomal replication. In this case, new combinations of alleles
are not produced since the sister chromosomes are usually identical. In
meiosis and mitosis, recombination occurs between similar molecules of DNA (homologous sequences).
In meiosis, non-sister homologous chromosomes pair with each other so
that recombination characteristically occurs between non-sister
homologues. In both meiotic and mitotic cells, recombination between
homologous chromosomes is a common mechanism used in DNA repair.
Gene conversion – the process during which homologous sequences are made identical also falls under genetic recombination.
During meiosis, synapsis (the pairing of homologous chromosomes) ordinarily precedes genetic recombination.
Mechanism
Genetic recombination is catalyzed by many different enzymes. Recombinases are key enzymes that catalyse the strand transfer step during recombination. RecA, the chief recombinase found in Escherichia coli,
is responsible for the repair of DNA double strand breaks (DSBs). In
yeast and other eukaryotic organisms there are two recombinases required
for repairing DSBs. The RAD51 protein is required for mitotic and meiotic recombination, whereas the DNA repair protein, DMC1, is specific to meiotic recombination. In the archaea, the ortholog of the bacterial RecA protein is RadA.
In bacteria there is regular genetic recombination, as well as ineffective transfer of genetic material, expressed as unsuccessful transfer or abortive transfer, which is any bacterial DNA transfer of the donor cell to recipients which have set the incoming DNA as part of the genetic material of the recipient. Abortive transfer was registered in the following transduction and conjugation. In all cases, the transmitted fragment is diluted by the culture growth.
In eukaryotes, recombination during meiosis is facilitated by chromosomal crossover.
The crossover process leads to offspring having different combinations
of genes from those of their parents, and can occasionally produce new chimericalleles. The shuffling of genes brought about by genetic recombination produces increased genetic variation. It also allows sexually reproducing organisms to avoid Muller's ratchet, in which the genomes of an asexualpopulation tend to accumulate deleterious mutations over time than beneficial or reversing mutations.
Chromosomal crossover involves recombination between the paired chromosomes inherited from each of one's parents, generally occurring during meiosis. During prophase I (pachytene stage) the four available chromatids are in tight formation with one another. While in this formation, homologous sites on two chromatids can closely pair with one another, and may exchange genetic information.
Because there is a small probability of recombination at any location along a chromosome, the frequency of recombination between two locations depends on the distance separating them.
Therefore, for genes sufficiently distant on the same chromosome, the
amount of crossover is high enough to destroy the correlation between
alleles.
Tracking the movement of genes resulting from crossovers has
proven quite useful to geneticists. Because two genes that are close
together are less likely to become separated than genes that are farther
apart, geneticists can deduce roughly how far apart two genes are on a
chromosome if they know the frequency of the crossovers.
Geneticists can also use this method to infer the presence of certain
genes. Genes that typically stay together during recombination are said
to be linked.
One gene in a linked pair can sometimes be used as a marker to deduce
the presence of the other gene. This is typically used to detect the
presence of a disease-causing gene.
The recombination frequency between two loci observed is the crossing-over value. It is the frequency of crossing over between two linked gene loci (markers), and depends on the distance between the genetic loci
observed. For any fixed set of genetic and environmental conditions,
recombination in a particular region of a linkage structure (chromosome) tends to be constant, and the same is then true for the crossing-over value which is used in the production of genetic maps.
In gene conversion, a section of genetic material is copied from one
chromosome to another, without the donating chromosome being changed.
Gene conversion occurs at high frequency at the actual site of the
recombination event during meiosis.
It is a process by which a DNA sequence is copied from one DNA helix
(which remains unchanged) to another DNA helix, whose sequence is
altered. Gene conversion has often been studied in fungal crosses
where the 4 products of individual meioses can be conveniently
observed. Gene conversion events can be distinguished as deviations in
an individual meiosis from the normal 2:2 segregation pattern (e.g. a
3:1 pattern).
Nonhomologous recombination
Recombination can occur between DNA sequences that contain no sequence homology. This can cause chromosomal translocations, sometimes leading to cancer.
In genetic engineering,
recombination can also refer to artificial and deliberate recombination
of disparate pieces of DNA, often from different organisms, creating
what is called recombinant DNA. A prime example of such a use of genetic recombination is gene targeting, which can be used to add, delete or otherwise change an organism's genes. This technique is important to biomedical researchers as it allows them to study the effects of specific genes. Techniques based on genetic recombination are also applied in protein engineering to develop new proteins of biological interest.
DNA damages caused by a variety of exogenous agents (e.g. UV light, X-rays, chemical cross-linking agents) can be repaired by homologous recombinational repair (HRR). These findings suggest that DNA damages arising from natural processes,
such as exposure to reactive oxygen species that are byproducts of
normal metabolism, are also repaired by HRR. In humans, deficiencies in
the gene products necessary for HRR during meiosis likely cause
infertility In humans, deficiencies in gene products necessary for HRR, such as BRCA1 and BRCA2, increase the risk of cancer (see DNA repair-deficiency disorder).
In bacteria, transformation is a process of gene transfer that
ordinarily occurs between individual cells of the same bacterial
species. Transformation involves integration of donor DNA into the
recipient chromosome by recombination. This process appears to be an
adaptation for repairing DNA damages in the recipient chromosome by HRR.
Transformation may provide a benefit to pathogenic bacteria by
allowing repair of DNA damage, particularly damages that occur in the
inflammatory, oxidizing environment associated with infection of a host.
When two or more viruses, each containing lethal genomic damages,
infect the same host cell, the virus genomes can often pair with each
other and undergo HRR to produce viable progeny. This process, referred
to as multiplicity reactivation, has been studied in lambda and T4 bacteriophages,
as well as in several pathogenic viruses. In the case of pathogenic
viruses, multiplicity reactivation may be an adaptive benefit to the
virus since it allows the repair of DNA damages caused by exposure to
the oxidizing environment produced during host infection. See also reassortment.
Meiotic recombination
A molecular model for the mechanism of meiotic recombination presented by Anderson and Sekelsky
is outlined in the first figure in this article. Two of the four
chromatids present early in meiosis (prophase I) are paired with each
other and able to interact. Recombination, in this model, is initiated
by a double-strand break (or gap) shown in the DNA molecule (chromatid)
at the top of the figure. Other types of DNA damage may also initiate
recombination. For instance, an inter-strand cross-link (caused by
exposure to a cross-linking agent such as mitomycin C) can be repaired
by HRR.
Two types of recombinant product are produced. Indicated on the
right side is a "crossover" (CO) type, where the flanking regions of the
chromosomes are exchanged, and on the left side, a "non-crossover"
(NCO) type where the flanking regions are not exchanged. The CO type of
recombination involves the intermediate formation of two "Holliday
junctions" indicated in the lower right of the figure by two X-shaped
structures in each of which there is an exchange of single strands
between the two participating chromatids. This pathway is labeled in the
figure as the DHJ (double-Holliday junction) pathway.
The NCO recombinants (illustrated on the left in the figure) are
produced by a process referred to as "synthesis dependent strand
annealing" (SDSA). Recombination events of the NCO/SDSA type appear to
be more common than the CO/DHJ type.
The NCO/SDSA pathway contributes little to genetic variation, since the
arms of the chromosomes flanking the recombination event remain in the
parental configuration. Thus, explanations for the adaptive function of
meiosis that focus exclusively on crossing-over are inadequate to
explain the majority of recombination events.
Achiasmy and heterochiasmy
Achiasmy
is the phenomenon where autosomal recombination is completely absent in
one sex of a species. Achiasmatic chromosomal segregation is well
documented in male Drosophila melanogaster. Heterochiasmy occurs when recombination rates differ between the sexes of a species.
This sexual dimorphic pattern in recombination rate has been observed
in many species. In mammals, females most often have higher rates of
recombination. The "Haldane-Huxley rule" states that achiasmy usually occurs in the heterogametic sex.
RNA virus recombination
Numerous RNA viruses are capable of genetic recombination when at least two viral genomes are present in the same host cell. Recombination is largely responsible for RNA virus diversity and immune evasion.
RNA recombination appears to be a major driving force in determining
genome architecture and the course of viral evolution among picornaviridae ((+)ssRNA) (e.g. poliovirus). In the retroviridae ((+)ssRNA)(e.g. HIV), damage in the RNA genome appears to be avoided during reverse transcription by strand switching, a form of recombination.
Recombination in RNA viruses appears to be an adaptation for coping with genome damage.
Switching between template strands during genome replication, referred
to as copy-choice recombination, was originally proposed to explain the
positive correlation of recombination events over short distances in
organisms with a DNA genome (see first Figure, SDSA pathway).
Recombination can occur infrequently between animal viruses of
the same species but of divergent lineages. The resulting recombinant
viruses may sometimes cause an outbreak of infection in humans.
Especially in coronaviruses, recombination may also occur even
among distantly related evolutionary groups (subgenera), due to their
characteristic transcription mechanism, that involves subgenomic mRNAs
that are formed by template switching.
When replicating its (+)ssRNA genome, the poliovirusRNA-dependent RNA polymerase
(RdRp) is able to carry out recombination. Recombination appears to
occur by a copy choice mechanism in which the RdRp switches (+)ssRNA
templates during negative strand synthesis. Recombination by RdRp strand switching also occurs in the (+)ssRNA plant carmoviruses and tombusviruses.
Recombination appears to be a major driving force in determining
genetic variability within coronaviruses, as well as the ability of
coronavirus species to jump from one host to another and, infrequently,
for the emergence of novel species, although the mechanism of
recombination in is unclear.
In early 2020, many genomic sequences of Australian SARS‐CoV‐2 isolates
have deletions or mutations (29742G>A or 29742G>U; "G19A" or
"G19U") in the s2m, suggesting that RNA recombination may have occurred
in this RNA element. 29742G("G19"), 29744G("G21"), and 29751G("G28")
were predicted as recombination hotspots.
During the first months of the COVID-19 pandemic, such a recombination
event was suggested to have been a critical step in the evolution of
SARS-CoV-2's ability to infect humans. Linkage disequilibrium analysis confirmed that RNA recombination
with the 11083G > T mutation also contributed to the increase of
mutations among the viral progeny. The findings indicate that the 11083G
> T mutation of SARS-CoV-2 spread during Diamond Princess shipboard quarantine and arose through de novo RNA recombination under positive selection pressure. In three patients on the Diamond Princess cruise, two mutations, 29736G > T and 29751G > T (G13 and G28) were located in Coronavirus 3′ stem-loop II-like motif (s2m)
of SARS-CoV-2. Although s2m is considered an RNA motif highly conserved
in 3' untranslated region among many coronavirus species, this result
also suggests that s2m of SARS-CoV-2 is RNA recombination/mutation hotspot.
Schematic
representation of the s2m RNA secondary structure, with tertiary
structural interactions indicated as long range contacts.
SARS-CoV-2's entire receptor binding motif appeared, based on
preliminary observations, to have been introduced through recombination
from coronaviruses of pangolins.
However, more comprehensive analyses later refuted this suggestion and
showed that SARS-CoV-2 likely evolved solely within bats and with
little or no recombination.
Role of recombination in the origin of life
Nowak and Ohtsuki noted that the origin of life (abiogenesis) is also the origin of biological evolution. They pointed out that all known life on earth is based on biopolymers
and proposed that any theory for the origin of life must involve
biological polymers that act as information carriers and catalysts.
Lehman argued that recombination was an evolutionary development as ancient as the origins of life. Smail et al.
proposed that in the primordial Earth, recombination played a key role
in the expansion of the initially short informational polymers (presumed
to be RNA) that were the precursors to life.
The first universal common ancestor (FUCA) is a proposed non-cellular entity that was the earliest organism with a genetic code capable of biological translation of RNA molecules into peptides to produce proteins. Its descendents include the last universal common ancestor (LUCA) and every modern cell.
FUCA would also be the ancestor of ancient sister lineages of LUCA,
none of which have modern descendants, but which are thought to have horizontally transferred some of their genes into the genome of early descendants of LUCA.
FUCA is thought to have been composed of progenotes, proposed ancient biological systems that would have used RNA for their genome and self-replication. By comparison, LUCA would have had a complex metabolism and a DNA genome with hundreds of genes and gene families.
Origins
Long
before the appearance of compartmentalized biological entities like
FUCA, life had already began to organize itself and emerge in a pre-cellular era known as the RNA world. The universal presence of both biological translation mechanism and genetic code in every biological systems indicates monophyly, a unique origin for all biological systems including viruses and cells.
FUCA would have been the first organism capable of biological translation, using RNA molecules to convert information into peptides and produce proteins. This first translation system would have been assembled together with primeval, possibly error-prone genetic code. That is, FUCA would be the first biological system to have genetic code for proteins.
The first genes of FUCA were most likely encoding ribosomal, primitive tRNA-aminoacyl transferases and other proteins that helped to stabilize and maintain biological translation. These random peptides produced possibly bound back to the single strand nucleic acid
polymers and allowed a higher stabilization of the system that got more
robust and was further bound to other stabilizing molecules. When FUCA had matured, its genetic code was completely established.
FUCA was composed by a population of open-systems, self-replicating ribonucleoproteins. With the arrival of these systems, began the progenote era. These systems evolved into maturity when self-organization processes resulted in the creation of a genetic code. This genetic code was for the first time capable to organize an ordered interaction between nucleic acids and proteins through the formation of a biological language.
This caused pre-cellular open systems to then start to accumulate
information and self-organize, producing the first genomes by the
assembly of biochemical pathways, which probably appeared in different progenote populations evolving independently.
Progenotes (also called ribocytes or ribocells)
are semi-open or open biological systems capable of performing an
intense exchange of genetic information, before the existence of cells
and LUCA. The term progenote was coined by Carl Woese in 1977, around the time he introduced the concept of the three domains of life (bacteria, archaea, and eukaryotes) and proposed that each domain originated from a different progenote. The meaning of the term changed with time. In the 1980s, Doolittle and Darnell used the word progenote to designate the ancestor of all three domains of life, now referred to as the last universal common ancestor (LUCA).
The terms ribocyte and ribocell refer to progenotes as protoribosomes, primeval ribosomes that were hypothetical cellular organisms with self-replicating RNA but without DNA, and thus with a RNA genome instead of the usual DNA genome. In Carl Woese's Darwinian threshold period of cellular evolution, the progenotes are also thought to have had RNA as informational molecule instead of DNA.
The evolution of the ribosome from ancient ribocytes, self-replicating machines,
into its current form as a translational machine may have been the
selective pressure to incorporate proteins into the ribosome's
self-replicating mechanisms, so as to increase its capacity for
self-replication. Ribosomal RNA is thought to have emerged before cells or viruses, at the time of progenotes.
Progenotes composed and were the descendants of FUCA,
and FUCA is thought to have organized the process between the initial
organization of biological systems and the maturation of progenotes. Progenotes were dominants in the Progenote age, the time where biological systems originated and initially assembled. The Progenote age would have happened after the pre-biotic age of the RNA-world and Peptide-world but before the age of organisms and mature biological systems like viruses, bacteria and archaea.
The most successful progenotes populations were probably the ones capable to bind and process carbohydrates, amino acids and other intermediated metabolites and co-factors. In progenotes, compartmentalization with membranes
was not yet completed and translation of proteins was not precise. Not
every progenote had its own metabolism; different metabolic steps were
present in different progenotes. Therefore, it is assumed that there
existed a community of sub-systems that started to cooperate
collectively and culminated in the LUCA.
Ribocytes and viruses
In the eocyte hypothesis, the organism at the root of all eocytes
may have been a ribocyte of the RNA-world. For cellular DNA and DNA
handling, an "out of virus" scenario has been proposed: storing genetic
information in DNA may have been an innovation performed by viruses and
later handed over to ribocytes twice, once transforming them into
bacteria and once transforming them into archaea.
Similarly in viral eukaryogenesis, a hypothesis theorizing that eukaryotes evolved from a DNA Virus, ribocytes may have been an ancient host for the DNA virus. As ribocytes used RNA to store their genetic info, viruses may initially have adopted DNA as a way to resist RNA-degradingenzymes in the host ribocells. Hence, the contribution from such a new component may have been as significant as the contribution from chloroplasts or mitochondria. Following this hypothesis, archaea, bacteria, and eukaryotes each obtained their DNA informational system from a different virus.
Also, new epithelium is formed here, which is important because
the cells at this site are continuously worn away by the passing food.
The basal (further from the intestinal lumen) portion of the crypt contains multipotent stem cells. During each mitosis,
one of the two daughter cells remains in the crypt as a stem cell,
while the other differentiates and migrates up the side of the crypt and
eventually into the villus. These stem cells can differentiate into either an absorptive (enterocytes) or secretory (Goblet cells, Paneth cells, enteroendocrine cells) lineages. Both Wnt and Notch signaling pathways play a large role in regulating cell proliferation and in intestinal morphogenesis and homeostasis.
Loss of proliferation control in the crypts is thought to lead to colorectal cancer.
Intestinal juice
Intestinal juice (also called succus entericus) refers to the clear to pale yellow watery secretions from the glands lining the small intestine walls. The Brunner's glands
secrete large amounts of alkaline mucus in response to (1) tactile or
irritating stimuli on the duodenal mucosa; (2) vagal stimulation, which
increases Brunner's glands secretion concurrently with increase in
stomach secretion; and (3) gastrointestinal hormones, especially secretin.
Its function is to complete the process begun by pancreatic juice; the enzymetrypsin exists in pancreatic juice in the inactive form trypsinogen, it is activated by the intestinal enterokinase in intestinal juice. Trypsin can then activate other protease enzymes and catalyze the reaction pro-colipase → colipase. Colipase is necessary, along with bile salts, to enable lipase function.
Colonic crypts (intestinal glands) within four tissue sections. In panel A, the bar shows 100 μm
and allows an estimate of the frequency of crypts in the colonic
epithelium. Panel B includes three crypts in cross-section, each with
one segment deficient for CCOI expression and at least one crypt, on the
right side, undergoing fission into two crypts. Panel C shows, on the
left side, a crypt fissioning into two crypts. Panel D shows typical
small clusters of two and three CCOI deficient crypts (the bar shows 50
μm). The images were made from original photomicrographs, but panels A, B
and D were also included in an article
The intestinal glands in the colon are often referred to as colonic crypts. The epithelial
inner surface of the colon is punctuated by invaginations, the colonic
crypts. The colon crypts are shaped like microscopic thick-walled test
tubes with a central hole down the length of the tube (the crypt lumen).
Four tissue sections are shown here, two (A and B) cut across the long
axes of the crypts and two (C and D) cut parallel to the long axes.
In these images the cells have been stained to show a brown-orange color if the cells produce a mitochondrial protein called cytochrome c oxidase subunit I (CCOI or COX-1). The nuclei of the cells (located at the outer edges of the cells lining the walls of the crypts) are stained blue-gray with haematoxylin. As seen in panels C and D, crypts are about 75 to about 110 cells long. The average crypt circumference is 23 cells.
From the images, an average is shown to be about 1,725 to 2530 cells
per colonic crypt. Another measure was attained giving a range of 1500
to 4900 cells per colonic crypt. Cells are produced at the crypt base and migrate upward along the crypt axis before being shed into the colonic lumen days later. There are 5 to 6 stem cells at the bases of the crypts.
As estimated from the image in panel A, there are about 100 colonic crypts per square millimeter of the colonic epithelium.
The length of the human colon is, on average 160.5 cm (measured from
the bottom of the cecum to the colorectal junction) with a range of
80 cm to 313 cm. The average inner circumference of the colon is 6.2 cm. Thus, the inner surface epithelial area of the human colon has an area, on average, of about 995 cm2, which includes 9,950,000 (close to 10 million) crypts.
In the four tissue sections shown here, many of the intestinal glands have cells with a mitochondrial DNA
mutation in the CCOI gene and appear mostly white, with their main
color being the blue-gray staining of the nuclei. As seen in panel B, a
portion of the stem cells of three crypts appear to have a mutation in
CCOI, so that 40% to 50% of the cells arising from those stem cells form
a white segment in the cross cut area.
Overall, the percentage of crypts deficient for CCOI is less than 1% before age 40, but then increases linearly with age. Colonic crypts deficient for CCOI reaches, on average, 18% in women and 23% in men, by 80–84 years of age.
Crypts of the colon can reproduce by fission, as seen in panel C,
where a crypt is dividing to form two crypts, and in panel B where at
least one crypt appears to be fissioning. Most crypts deficient in CCOI
are in clusters of crypts (clones of crypts) with two or more
CCOI-deficient crypts adjacent to each other (see panel D).
Intestinal glands contain adult stem cells referred to as intestinal stem cells. These cells have been used in the field of stem biology to further understand stem cell niches, and to generate intestinal organoids.
History
The crypts of Lieberkühn are named after the eighteenth-century German anatomist Johann Nathanael Lieberkühn.
Diagram of the digestive enzymes in the small intestine and pancreas
Digestive enzymes take part in the chemical process of digestion,
which follows the mechanical process of digestion. Food consists of
macromolecules of proteins, carbohydrates, and fats that need to be
broken down chemically by digestive enzymes in the mouth, stomach, pancreas, and duodenum, before being able to be absorbed into the bloodstream. Initial breakdown is achieved by chewing (mastication) and the use of digestive enzymes of saliva. Once in the stomach further mechanical churning takes place mixing the food with secreted gastric acid. Digestive gastric enzymes take part in some of the chemical process needed for absorption. Most of the enzymatic activity, and hence absorption takes place in the duodenum.
Digestive enzymes are found in the digestive tracts of animals (including humans) and in the tracts of carnivorous plants, where they aid in the digestion of food, as well as inside cells, especially in their lysosomes, where they function to maintain cellular survival.
Complex
food substances that are eaten must be broken down into simple, soluble,
and diffusible substances before they can be absorbed. In the oral
cavity, salivary glands secrete an array of enzymes and substances that
aid in digestion and also disinfection. They include the following:
Lingual lipase: Lipid digestion initiates in the mouth. Lingual lipase starts the digestion of the lipids/fats.
Salivary amylase:
Carbohydrate digestion also initiates in the mouth. Amylase, produced
by the salivary glands, breaks complex carbohydrates, mainly cooked
starch, to smaller chains, or even simple sugars. It is sometimes
referred to as ptyalin.
Lysozyme:
Considering that food contains more than just essential nutrients, e.g.
bacteria or viruses, the lysozyme offers a limited and non-specific,
yet beneficial antiseptic function in digestion.
Of note is the diversity of the salivary glands. There are two types of salivary glands:
Serous glands: These glands produce a secretion rich in water, electrolytes, and enzymes. A great example of a serous oral gland is the parotid gland.
Mixed glands: These glands have both serous cells and mucous cells, and include sublingual and submandibular glands. Their secretion is mucinous and high in viscosity.
Stomach
The enzymes that are secreted in the stomach are gastric enzymes.
The stomach plays a major role in digestion, both in a mechanical sense
by mixing and crushing the food, and also in an enzymatic sense, by
digesting it. The following are enzymes produced by the stomach and
their respective function:
Pepsin is the main gastric enzyme. It is produced by the stomach cells called "chief cells" in its inactive form pepsinogen, which is a zymogen.
Pepsinogen is then activated by the stomach acid into its active form,
pepsin. Pepsin breaks down the protein in the food into smaller
particles, such as peptide fragments and amino acids.
Protein digestion, therefore, primarily starts in the stomach, unlike
carbohydrate and lipids, which start their digestion in the mouth
(however, trace amounts of the enzyme kallikrein, which catabolises certain protein, is found in saliva in the mouth).
Gastric lipase: Gastric lipase is an acidic lipase secreted by the gastric chief cells in the fundic
mucosa of the stomach. It has a pH level of 3–6. Gastric lipase,
together with lingual lipase, comprise the two acidic lipases. These
lipases, unlike alkaline lipases (such as pancreatic lipase), do not require bile acid or colipase for optimal enzymatic activity. Acidic lipases make up 30% of lipid hydrolysis
occurring during digestion in the human adult, with gastric lipase
contributing the most of the two acidic lipases. In neonates, acidic
lipases are much more important, providing up to 50% of total lipolytic
activity.
"Pancreatic enzyme" and "pancrease" redirect to this discussion of endogenous forms. For exogenous forms, see Pancreatic enzymes (medication).
Pancreas is both an endocrine and an exocrine gland, in that it
functions to produce endocrinic hormones released into the circulatory
system (such as insulin, and glucagon),
to control glucose metabolism, and also to secrete digestive/exocrinic
pancreatic juice, which is secreted eventually via the pancreatic duct
into the duodenum. Digestive or exocrine function of pancreas is as
significant to the maintenance of health as its endocrine function.
Two of the population of cells in the pancreatic parenchyma make up its digestive enzymes:
Ductal cells: Mainly responsible for production of bicarbonate (HCO3),
which acts to neutralize the acidity of the stomach chyme entering
duodenum through the pylorus. Ductal cells of the pancreas are
stimulated by the hormone secretin
to produce their bicarbonate-rich secretions, in what is in essence a
bio-feedback mechanism; highly acidic stomach chyme entering the
duodenum stimulates duodenal cells called "S cells" to produce the
hormone secretin and release to the bloodstream. Secretin having
entered the blood eventually comes into contact with the pancreatic
ductal cells, stimulating them to produce their bicarbonate-rich juice.
Secretin also inhibits production of gastrin by "G cells", and also stimulates acinar cells of the pancreas to produce their pancreatic enzyme.
Acinar cells: Mainly responsible for production of the inactive pancreatic enzymes (zymogens)
that, once present in the small bowel, become activated and perform
their major digestive functions by breaking down proteins, fat, and
DNA/RNA. Acinar cells are stimulated by cholecystokinin
(CCK), which is a hormone/neurotransmitter produced by the intestinal
cells (I cells) in the duodenum. CCK stimulates production of the
pancreatic zymogens.
Pancreatic juice, composed of the secretions of both ductal and acinar cells, contains the following digestive enzymes:
Trypsinogen, which is an inactive(zymogenic) protease that, once activated in the duodenum into trypsin, breaks down proteins at the basic amino acids. Trypsinogen is activated via the duodenal enzyme enterokinase into its active form trypsin.
Chymotrypsinogen, which is an inactive (zymogenic) protease that, once activated by duodenal enterokinase, turns into chymotrypsin and breaks down proteins at their aromatic amino acids. Chymotrypsinogen can also be activated by trypsin.
Carboxypeptidase, which is a protease that takes off the terminal amino acid group from a protein
Several elastases that degrade the protein elastin and some other proteins
Pancreatic amylase that breaks down starch and glycogen which are alpha-linked glucose polymers. Humans lack the cellulases to digest the carbohydrate cellulose which is a beta-linked glucose polymer.
The pancreas's exocrine function owes part of its notable
reliability to biofeedback mechanisms controlling secretion of the
juice. The following significant pancreatic biofeedback mechanisms are
essential to the maintenance of pancreatic juice balance/production:
Secretin,
a hormone produced by the duodenal "S cells" in response to the stomach
chyme containing high hydrogen atom concentration (high acidicity), is
released into the blood stream; upon return to the digestive tract,
secretion decreases gastric emptying, increases secretion of the
pancreatic ductal cells, as well as stimulating pancreatic acinar cells
to release their zymogenic juice.
Cholecystokinin
(CCK) is a unique peptide released by the duodenal "I cells" in
response to chyme containing high fat or protein content. Unlike
secretin, which is an endocrine hormone, CCK actually works via
stimulation of a neuronal circuit, the end-result of which is
stimulation of the acinar cells to release their content. CCK also
increases gallbladder contraction, resulting in bile squeezed into the cystic duct, common bile duct
and eventually the duodenum. Bile of course helps absorption of the fat
by emulsifying it, increasing its absorptive surface. Bile is made by
the liver, but is stored in the gallbladder.
Gastric inhibitory peptide (GIP) is produced by the mucosal duodenal cells in response to chyme containing high amounts of carbohydrate, proteins, and fatty acids. Main function of GIP is to decrease gastric emptying.
Somatostatin
is a hormone produced by the mucosal cells of the duodenum and also the
"delta cells" of the pancreas. Somatostatin has a major inhibitory
effect, including on pancreatic production.
Duodenum
The following enzymes/hormones are produced in the duodenum:
secretin: This is an endocrine hormone produced by the duodenal "S cells" in response to the acidity of the gastric chyme.
Cholecystokinin (CCK) is a unique peptide released by the duodenal
"I cells" in response to chyme containing high fat or protein content.
Unlike secretin, which is an endocrine hormone, CCK actually works via
stimulation of a neuronal circuit, the end-result of which is
stimulation of the acinar cells to release their content.
CCK also increases gallbladder contraction, causing release of
pre-stored bile into the cystic duct, and eventually into the common
bile duct and via the ampulla of Vater into the second anatomic position of the duodenum. CCK also decreases the tone of the sphincter of Oddi,
which is the sphincter that regulates flow through the ampulla of
Vater. CCK also decreases gastric activity and decreases gastric
emptying, thereby giving more time to the pancreatic juices to
neutralize the acidity of the gastric chyme.
Gastric inhibitory peptide (GIP): This peptide decreases gastric motility and is produced by duodenal mucosal cells.
motilin: This substance increases gastro-intestinal motility via specialized receptors called "motilin receptors".
somatostatin: This hormone is produced by duodenal mucosa and also by the delta cells of the pancreas. Its main function is to inhibit a variety of secretory mechanisms.
Throughout the lining of the small intestine there are numerous brush border
enzymes whose function is to further break down the chyme released from
the stomach into absorbable particles. These enzymes are absorbed
whilst peristalsis occurs. Some of these enzymes include:
Lactase:
This is a significant enzyme that converts lactose into glucose and
galactose. A majority of Middle-Eastern and Asian populations lack this
enzyme. This enzyme also decreases with age. As such lactose intolerance
is often a common abdominal complaint in the Middle-Eastern, Asian, and
older populations, manifesting with bloating, abdominal pain, and osmotic diarrhea.
Sucrase: converts sucrose into glucose and fructose.
Other disaccharidases
Plants
In carnivorous plants, digestive enzymes and acids break down insects and in some plants small animals. In some plants, the leaf collapses on the prey to increase contact, others have a small vessel of digestive liquid. Then digestion fluids are used to digest the prey to get at the needed nitrates and phosphorus.
The absorption of the needed nutrients are usually more efficient than
in other plants. Digestive enzymes independently came about in
carnivorous plants and animals.
Some carnivorous plants like the Heliamphora do not use digestive enzymes, but use bacteria to break down the food. These plants do not have digestive juices, but use the rot of the prey.
