Science, discussed.

Rate of protein evolution is determined by functional importance and constraints.

After the evolution of DNA sequencing technologies, recording genotype on a large scale has become possible and ever so cheaper too. The the large influx of genomics data resulted in booming research in molecular evolution in recent few years [1].

Molecular evolution underlies the emergent property of organismal evolution. Incremental tweaking of bio-molecules governed by natural selection – through time – results in the evolution of an organism itself. This fundamental phenomenon captures the imagination of many researchers. Last week a review was published in Nature Reviews Genetics which asks a burning question – “What determines the rate of molecular evolution?”

Determinants of the rate of protein sequence evolution
Jianzhi Zhang & Jian-Rong Yang 
Nature Reviews Genetics 09 June 2015

Rate of evolution of a gene is basically a complex function of the efficiencies of processes associated with pre and post expression of the gene. Even though some parts of puzzle are solved, how exactly the whole dynamics played out is still unclear. This review attempts to offer an integrative view of protein evolution. I have summarized some of the key points of the discussion.

The main focus of the review is on following two aspects of genes functionalities.


Functional constraint: owing to expression of a gene.

Functional constraint are costs of expression such as possibility of mis-translation, mis-folding or mis-interactions. Genes with higher rates of evolution would have weaker functional constraints and vice versa. Such genes would have lesser expression errors and hence less likely to purge out incoming mutations.

It is also known that genes expressed at high levels result in higher fitness costs upon  a deleterious mutation as compared to genes expressed at low levels. So there are stronger functional constraints on evolution of highly expressed genes. This could be a reason for a stronger anti-correlation observed between expression and evolutionary rate (E-R).

Also as an adaptive response, a cell could increase rate of evolution of a gene by increasing the robustness of the cellular processes such as translation, folding and protein-protein-interactions (PPI) as well as increasing structural robustness of mRNAs and proteins by chaperoning.

Functional constraints are mainly associated with expression of a functional protein. The later part is termed as functional importance.

Functional importance: owing to activity of a gene.

Functional importance, in simple terms is essentiality of a gene. It has been widely observed that genes with lower functional importance have higher rates of evolution and vice versa. Such genes are highly likely to have lower connectivity, closeness and betweenness in PPI networks and hence show higher dispensability.

From empirical data available till date, across different organismal systems, it is also evident that this anti-correlation is remarkably weaker as compared to that in case of E-R anti-correlation. Part of the reason for this could be a possibility of weak correlation between expression and function importance.

So collectively the fitness changes owing to functional constraints and functional importance determine the rate of protein evolution. It is also important to note that both of these features are mutually coupled and hence very difficult to test empirically. Especially the role of functional constraints which include expression errors and noise is relatively lesser-explored avenue of research and leading to many recent interesting discoveries. Also even though, cellular errors are taken care by natural selection itself, there are cases of increased error rates for example – in case of somatic mutations leading to aging, cancer and many other diseases – which demand a comprehensive research.

Comments are welcome.

Notes: [1]


Rise in the impact factor of ‘Molecular Biology And Evolution’.  Data source:



This entry was posted on 26/06/2015 by in Molecular Evolution, postprintreview and tagged , , .


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