scholarly journals Molecular evolution in small steps under prevailing negative selection – A nearly-universal rule of codon substitution

2019 ◽  
Author(s):  
Qingjian Chen ◽  
Ao Lan ◽  
Xu Shen ◽  
Chung-I Wu

AbstractThe widely accepted view that evolution proceeds in small steps is based on two premises: i) negative selection acts strongly against large differences (Kimura 1983); and ii) positive selection favors small-step changes (Fisher 1930). The two premises are not biologically connected and should be evaluated separately. We now extend the approach of Tang et al. (2004) to codon evolution for the entire genome. Codon substitution rate is a function of the physico-chemical distance between amino acids (AAs), equated with the step size of evolution. This step size depends on a large number of physico-chemical properties as 46 of the 48 properties examined affect the rate. Between 9 pairs of closely-related species of plants, invertebrates and vertebrates, the evolutionary rate is indeed strongly andnegativelycorrelated with the AA distance (ΔU, scaled to [0, 1]). While the analyses corroborate the published results that relied on partial genomes, there is an important difference: ΔUis strongly correlated with the evolutionary rate (R2> 0.8) only when the genes are under predominant negative selection. Nevertheless, since most genes in most taxa are strongly constrained by negative selection, ΔUwould appear to be a nearly-universal measure of codon evolution. In conclusion, the driving force of the small-step evolution at the codon level is negative selection. The unanswered question of whether positive selection may, or may not, follow the small-step rule will be addressed in a companion study (Chen, et al. 2019).

2019 ◽  
Vol 11 (10) ◽  
pp. 2702-2712 ◽  
Author(s):  
Qingjian Chen ◽  
Ao Lan ◽  
Xu Shen ◽  
Chung-I Wu

Abstract The widely accepted view that evolution proceeds in small steps is based on two premises: 1) negative selection acts strongly against large differences and 2) positive selection favors small-step changes. The two premises are not biologically connected and should be evaluated separately. We now extend a previous approach to studying codon evolution in the entire genome. Codon substitution rate is a function of the physicochemical distance between amino acids (AAs), equated with the step size of evolution. Between nine pairs of closely related species of plants, invertebrates, and vertebrates, the evolutionary rate is strongly and negatively correlated with a set of AA distances (ΔU, scaled to [0, 1]). ΔU, a composite measure of evolutionary rates across diverse taxa, is influenced by almost all of the 48 physicochemical properties used here. The new analyses reveal a crucial trend hidden from previous studies: ΔU is strongly correlated with the evolutionary rate (R2 > 0.8) only when the genes are predominantly under negative selection. Because most genes in most taxa are strongly constrained by negative selection, ΔU has indeed appeared to be a nearly universal measure of codon evolution. In conclusion, molecular evolution at the codon level generally takes small steps due to the prevailing negative selection. Whether positive selection may, or may not, follow the small-step rule is addressed in a companion study.


2019 ◽  
Author(s):  
Qingjian Chen ◽  
Ziwen He ◽  
Ao Lan ◽  
Haijun Wen ◽  
Chung-I Wu

AbstractMolecular evolution is believed to proceed in small steps. The step size can be defined by a distance reflecting physico-chemical disparities between amino acid (AA) pairs that can be exchanged by single 1 bp mutations. We show that AA substitution rates are strongly and negatively correlated with this distance but only when positive selection is relatively weak. We use the McDonald and Kreitman (MK) test to separate the influences of positive and negative selection. While negative selection is indeed stronger on AA substitutions generating larger changes in chemical properties of amino acids, positive selection operates by different rules. For 65 of the 75 possible pairs, positive selection is comparable in strength regardless of AA distance. However, the 10 pairs under the strongest positive selection all exhibit large leaps in chemical properties. Five of the 10 pairs are shared between hominoids andDrosophila, thus hinting at a common but modest biochemical basis of adaptation across taxa. The hypothesis that adaptive changes often take large functional steps will need to be extensively tested. If validated, molecular models will need to better integrate positive and negative selection in the search for adaptive signal.


2019 ◽  
Vol 36 (9) ◽  
pp. 1862-1873 ◽  
Author(s):  
Qingjian Chen ◽  
Ziwen He ◽  
Ao Lan ◽  
Xu Shen ◽  
Haijun Wen ◽  
...  

AbstractMolecular evolution is believed to proceed in small steps. The step size can be defined by a distance reflecting physico-chemical disparities between amino acid (AA) pairs that can be exchanged by single 1-bp mutations. We show that AA substitution rates are strongly and negatively correlated with this distance but only when positive selection is relatively weak. We use the McDonald and Kreitman test to separate the influences of positive and negative selection. While negative selection is indeed stronger on AA substitutions generating larger changes in chemical properties of AAs, positive selection operates by different rules. For 65 of the 75 possible pairs, positive selection is comparable in strength regardless of AA distance. However, the ten pairs under the strongest positive selection all exhibit large leaps in chemical properties. Five of the ten pairs are shared between Drosophila and Hominoids, thus hinting at a common but modest biochemical basis of adaptation across taxa. The hypothesis that adaptive changes often take large functional steps will need to be extensively tested. If validated, molecular models will need to better integrate positive and negative selection in the search for adaptive signal.


2015 ◽  
Author(s):  
Stephane Guindon

In a recent study, Murrell et al. (2015) compared the performance of several branch-site models of codon evolution. Their interpretation of results published by Lu & Guindon (2014) suggests that the stochastic branch-site model implemented in the software fitmodel is anti-conservative altogether, i.e., positive selection is detected more often than expected when analyzing sequences evolving under a mixture of neutrality and negative selection. I argue here that this presentation of the performance of fitmodel is misleading and should not deter evolutionary biologists from using this approach in exploratory analyses of selection patterns at the molecular level.


2015 ◽  
Author(s):  
Stephane Guindon

In a recent study, Murrell et al. (2015) compared the performance of several branch-site models of codon evolution. Their interpretation of results published by Lu & Guindon (2014) suggests that the stochastic branch-site model implemented in the software fitmodel is anti-conservative altogether, i.e., positive selection is detected more often than expected when analyzing sequences evolving under a mixture of neutrality and negative selection. I argue here that this presentation of the performance of fitmodel is misleading and should not deter evolutionary biologists from using this approach in exploratory analyses of selection patterns at the molecular level.


Author(s):  
H. Gross ◽  
H. Moor

Fracturing under ultrahigh vacuum (UHV, p ≤ 10-9 Torr) produces membrane fracture faces devoid of contamination. Such clean surfaces are a prerequisite foe studies of interactions between condensing molecules is possible and surface forces are unequally distributed, the condensate will accumulate at places with high binding forces; crystallites will arise which may be useful a probes for surface sites with specific physico-chemical properties. Specific “decoration” with crystallites can be achieved nby exposing membrane fracture faces to water vopour. A device was developed which enables the production of pure water vapour and the controlled variation of its partial pressure in an UHV freeze-fracture apparatus (Fig.1a). Under vaccum (≤ 10-3 Torr), small container filled with copper-sulfate-pentahydrate is heated with a heating coil, with the temperature controlled by means of a thermocouple. The water of hydration thereby released enters a storage vessel.


1990 ◽  
Vol 63 (03) ◽  
pp. 499-504 ◽  
Author(s):  
A Electricwala ◽  
L Irons ◽  
R Wait ◽  
R J G Carr ◽  
R J Ling ◽  
...  

SummaryPhysico-chemical properties of recombinant desulphatohirudin expressed in yeast (CIBA GEIGY code No. CGP 39393) were reinvestigated. As previously reported for natural hirudin, the recombinant molecule exhibited abnormal behaviour by gel filtration with an apparent molecular weight greater than that based on the primary structure. However, molecular weight estimation by SDS gel electrophoresis, FAB-mass spectrometry and Photon Correlation Spectroscopy were in agreement with the theoretical molecular weight, with little suggestion of dimer or aggregate formation. Circular dichroism studies of the recombinant molecule show similar spectra at different pH values but are markedly different from that reported by Konno et al. (13) for a natural hirudin-variant. Our CD studies indicate the presence of about 60% beta sheet and the absence of alpha helix in the secondary structure of recombinant hirudin, in agreement with the conformation determined by NMR studies (17)


1963 ◽  
Vol 79 (2) ◽  
pp. 263-293 ◽  
Author(s):  
E.M. Savitskii ◽  
V.F. Terekhova ◽  
O.P. Naumkin

1990 ◽  
Vol 39 (442) ◽  
pp. 996-1000 ◽  
Author(s):  
Ayao TAKASAKA ◽  
Hideyuki NEMOTO ◽  
Hirohiko KONO ◽  
Yoshihiro MATSUDA

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