The MT-COI protein, also known as CCOI, is usually expressed at a high level in the cytoplasm of colonic crypts of the human large intestine (colon).
 However, MT-COI is frequently lost in colonic crypts with age in humans and is also often absent in field defects that give rise to colon cancers as well as in portions of colon cancers.

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 in the image in this section, two cut across the long axes of the crypts and two cut parallel to the long axes.

Most of the human colonic crypts in the images have high expression of the brown-orange stained MT-COI.
 However, in some of the colonic crypts all of the cells lack MT-COI and appear mostly white, with their main color being the blue-gray staining of the nuclei at the outer walls of the crypts.
 Greaves et al.
showed that deficiencies of MT-COI in colonic crypts are due to mutations in the MT-COI gene.
 As seen in panel B, a portion of the stem cells of three crypts appear to have a mutation in MT-COI, so that 40% to 50% of the cells arising from those stem cells form a white segment in the cross-cut area.

In humans, the percent of colonic crypts deficient for MT-COI is less than 1% before age 40, but then increases linearly with age.
 On average, the percent of colonic crypts deficient for MT-COI reaches 18% in women and 23% in men by 80–84 years of age.
 Colonic tumors often arise in a field of crypts containing a large cluster (as many as 410) of MT-COI-deficient crypts.
 In colonic cancers, up to 80% of tumor cells can be deficient in MT-COI.

As seen in panels C and D, crypts are about 75 to about 110 cells long.
The average crypt circumference is 23 cells.
 Based on these measurements, crypts have between 1725 and 2530  cells.
 Another report gave a range of 1500 to 4900 cells per colonic crypt.

The occurrence of frequent crypts with almost complete loss of MT-COI in their 1700 to 5,000 cells suggests a process of natural selection.
 However, it has also been shown that a deficiency throughout a particular crypt due to an initial mitochondrial DNA mutation may occasionally occur through a stochastic process.
 Nevertheless, the frequent occurrence of MT-COI deficiency in many crypts within a colon epithelium indicates that absence of MT-COI likely provides a selective advantage.

MT-COI is coded for by the mitochondrial chromosome.
 There are multiple copies of the chromosome in most mitochondria, usually between 2 and 6 per mitochondrion.
 If a mutation occurs in MT-COI in one chromosome of a mitochondrion, there may be random segregation of the chromosomes during mitochondrial fission to generate new mitochondria.
 This can give rise to a mitochondrion with primarily or solely MT-COI-mutated chromosomes.

A mitochondrion with largely MT-COI-mutated chromosomes would need to have a positive selection bias in order to frequently become the main type of mitochondrion in a cell (a cell with MT-COI-deficient homoplasmy).
 There are about 100 to 700 mitochondria per cell, depending on cell type.
 Furthermore, there is fairly rapid turnover of mitochondria, so that a mitochondrion with MT-COI-mutated chromosomes and a positive selection bias could shortly become the major type of mitochondrion in a cell.
 The average half-life of mitochondria in rats, depending on cell type, is between 9 and 24 days, and in mice is about 2 days.
In humans it is likely that the half life of mitochondria is also a matter of days to weeks.

A stem cell at the base of a colonic crypt that was largely MT-COI-deficient may compete with the other 4 or 5 stem cells to take over the stem cell niche.
 If this occurs, then the colonic crypt would be deficient in MT-COI in all 1700 to 5,000 cells, as is indicated for some crypts in panels A, B and D of the image.

Crypts of the colon can reproduce by fission, as seen in panel C, where a crypt is fissioning
The MT-COI protein, also known as CCOI, is usually expressed at a high level in the cytoplasm of colonic crypts of the human large intestine (colon).  However, MT-COI is frequently lost in colonic crypts with age in humans and is also often absent in field defects that give rise to colon cancers as well as in portions of colon cancers.
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 in the image in this section, two cut across the long axes of the crypts and two cut parallel to the long axes.
Most of the human colonic crypts in the images have high expression of the brown-orange stained MT-COI.  However, in some of the colonic crypts all of the cells lack MT-COI and appear mostly white, with their main color being the blue-gray staining of the nuclei at the outer walls of the crypts.  Greaves et al. showed that deficiencies of MT-COI in colonic crypts are due to mutations in the MT-COI gene.  As seen in panel B, a portion of the stem cells of three crypts appear to have a mutation in MT-COI, so that 40% to 50% of the cells arising from those stem cells form a white segment in the cross-cut area.
In humans, the percent of colonic crypts deficient for MT-COI is less than 1% before age 40, but then increases linearly with age.  On average, the percent of colonic crypts deficient for MT-COI reaches 18% in women and 23% in men by 80–84 years of age.  Colonic tumors often arise in a field of crypts containing a large cluster (as many as 410) of MT-COI-deficient crypts.  In colonic cancers, up to 80% of tumor cells can be deficient in MT-COI.
As seen in panels C and D, crypts are about 75 to about 110 cells long. The average crypt circumference is 23 cells.  Based on these measurements, crypts have between 1725 and 2530  cells.  Another report gave a range of 1500 to 4900 cells per colonic crypt.
The occurrence of frequent crypts with almost complete loss of MT-COI in their 1700 to 5,000 cells suggests a process of natural selection.  However, it has also been shown that a deficiency throughout a particular crypt due to an initial mitochondrial DNA mutation may occasionally occur through a stochastic process.  Nevertheless, the frequent occurrence of MT-COI deficiency in many crypts within a colon epithelium indicates that absence of MT-COI likely provides a selective advantage.
MT-COI is coded for by the mitochondrial chromosome.  There are multiple copies of the chromosome in most mitochondria, usually between 2 and 6 per mitochondrion.  If a mutation occurs in MT-COI in one chromosome of a mitochondrion, there may be random segregation of the chromosomes during mitochondrial fission to generate new mitochondria.  This can give rise to a mitochondrion with primarily or solely MT-COI-mutated chromosomes.
A mitochondrion with largely MT-COI-mutated chromosomes would need to have a positive selection bias in order to frequently become the main type of mitochondrion in a cell (a cell with MT-COI-deficient homoplasmy).  There are about 100 to 700 mitochondria per cell, depending on cell type.  Furthermore, there is fairly rapid turnover of mitochondria, so that a mitochondrion with MT-COI-mutated chromosomes and a positive selection bias could shortly become the major type of mitochondrion in a cell.  The average half-life of mitochondria in rats, depending on cell type, is between 9 and 24 days, and in mice is about 2 days. In humans it is likely that the half life of mitochondria is also a matter of days to weeks.
A stem cell at the base of a colonic crypt that was largely MT-COI-deficient may compete with the other 4 or 5 stem cells to take over the stem cell niche.  If this occurs, then the colonic crypt would be deficient in MT-COI in all 1700 to 5,000 cells, as is indicated for some crypts in panels A, B and D of the image.
Crypts of the colon can reproduce by fission, as seen in panel C, where a crypt is fissioning
Cytochrome c oxidase subunit I