---
_id: '843'
abstract:
- lang: eng
text: The impact of an amino acid replacement on the organism's fitness can vary
from lethal to selectively neutral and even, in rare cases, beneficial. Substantial
data are available on either pathogenic or acceptable replacements. However, the
whole distribution of coefficients of selection against individual replacements
is not known for any organism. To ascertain this distribution for human proteins,
we combined data on pathogenic missense mutations, on human non-synonymous SNPs
and on human-chimpanzee divergence of orthologous proteins. Fractions of amino
acid replacements which reduce fitness by >10-2, 10-2-10-4, 10-4-10-5 and <10-5
are 25, 49, 14 and 12%, respectively. On average, the strength of selection against
a replacement is substantially higher when chemically dissimilar amino acids are
involved, and the Grantham's index of a replacement explains 35% of variance in
the average logarithm of selection coefficients associated with different replacements.
Still, the impact of a replacement depends on its context within the protein more
than on its own nature. Reciprocal replacements are often associated with rather
different selection coefficients, in particular, replacements of non-polar amino
acids with polar ones are typically much more deleterious than replacements in
the opposite direction. However, differences between evolutionary fluxes of reciprocal
replacements are only weakly correlated with the differences between the corresponding
selection coefficients.
author:
- first_name: Lev
full_name: Yampolsky, Lev Y
last_name: Yampolsky
- first_name: Fyodor
full_name: Fyodor Kondrashov
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
- first_name: Alexey
full_name: Kondrashov, Alexey S
last_name: Kondrashov
citation:
ama: Yampolsky L, Kondrashov F, Kondrashov A. Distribution of the strength of selection
against amino acid replacements in human proteins. Human Molecular Genetics.
2005;14(21):3191-3201. doi:10.1093/hmg/ddi350
apa: Yampolsky, L., Kondrashov, F., & Kondrashov, A. (2005). Distribution of
the strength of selection against amino acid replacements in human proteins. Human
Molecular Genetics. Oxford University Press. https://doi.org/10.1093/hmg/ddi350
chicago: Yampolsky, Lev, Fyodor Kondrashov, and Alexey Kondrashov. “Distribution
of the Strength of Selection against Amino Acid Replacements in Human Proteins.”
Human Molecular Genetics. Oxford University Press, 2005. https://doi.org/10.1093/hmg/ddi350.
ieee: L. Yampolsky, F. Kondrashov, and A. Kondrashov, “Distribution of the strength
of selection against amino acid replacements in human proteins,” Human Molecular
Genetics, vol. 14, no. 21. Oxford University Press, pp. 3191–3201, 2005.
ista: Yampolsky L, Kondrashov F, Kondrashov A. 2005. Distribution of the strength
of selection against amino acid replacements in human proteins. Human Molecular
Genetics. 14(21), 3191–3201.
mla: Yampolsky, Lev, et al. “Distribution of the Strength of Selection against Amino
Acid Replacements in Human Proteins.” Human Molecular Genetics, vol. 14,
no. 21, Oxford University Press, 2005, pp. 3191–201, doi:10.1093/hmg/ddi350.
short: L. Yampolsky, F. Kondrashov, A. Kondrashov, Human Molecular Genetics 14 (2005)
3191–3201.
date_created: 2018-12-11T11:48:48Z
date_published: 2005-11-01T00:00:00Z
date_updated: 2021-01-12T08:19:13Z
day: '01'
doi: 10.1093/hmg/ddi350
extern: 1
intvolume: ' 14'
issue: '21'
month: '11'
page: 3191 - 3201
publication: Human Molecular Genetics
publication_status: published
publisher: Oxford University Press
publist_id: '6807'
quality_controlled: 0
status: public
title: Distribution of the strength of selection against amino acid replacements in
human proteins
type: journal_article
volume: 14
year: '2005'
...