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A conservative replacement (also called a conservative mutation or a conservative substitution) is an amino acid replacement in a protein that changes a given
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
to a different amino acid with similar biochemical properties (e.g. charge,
hydrophobicity In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, t ...
and
size Size in general is the magnitude or dimensions of a thing. More specifically, ''geometrical size'' (or ''spatial size'') can refer to linear dimensions (length, width, height, diameter, perimeter), area, or volume. Size can also be measur ...
). Conversely, a radical replacement, or radical substitution, is an amino acid replacement that exchanges an initial amino acid by a final amino acid with different physicochemical properties.


Description

There are 20 naturally occurring amino acids, however some of these share similar characteristics. For example,
leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- c ...
and
isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...
are both
aliphatic In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, o ...
, branched
hydrophobe In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, th ...
s. Similarly,
aspartic acid Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
and
glutamic acid Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
are both small, negatively charged residues. Although there are many ways to classify amino acids, they are often sorted into six main classes on the basis of their structure and the general chemical characteristics of their side chains (R groups). Physicochemical distances aim at quantifying the intra-class and inter-class dissimilarity between amino acids based on their measurable properties, and many such measures have been proposed in the literature. Owing to their simplicity, two of the most commonly used measures are the ones of Grantham (1974) and Miyata et al (1979). A conservative replacement is therefore an exchange between two amino acids separated by a small physicochemical distance. Conversely, a radical replacement is an exchange between two amino acids separated by a large physicochemical distance.


Impact on function

Conservative replacements in proteins often have a better effect on function than non-conservative replacements. The reduced effect of conservative replacements on function can also be seen in the occurrence of different replacements in nature. Non-conservative replacements between proteins are far more likely to be removed by
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Charl ...
due to their deleterious effects.


See also

* Segregating site *
Ultra-conserved element An ultra-conserved element (UCE) was originally defined as a genome segment longer than 200 base pairs (bp) that is absolutely conserved, with no insertions or deletions and 100% identity, between orthologous regions of the human, rat, and mouse gen ...
*
Sequence alignment In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Ali ...
* Sequence alignment software


References

{{Mutation Biochemistry Amino acids