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Effect of genetic drift on determinants of protein evolution.

ABSTRACT: A number of previous studies reported that gene expression, tissue specificity, gene essentiality and the number of protein-protein interactions influence the rate of protein evolution. Here we investigated the influence of effective population size (Ne) on these determinants of protein evolution. For this purpose, we compared the ratio of non-synonymous-to-synonymous diversities (?N/?S) estimated for protein-coding genes of Mus musculus castaneus and Mus musculus musculus: populations with high and low Ne respectively. Our results revealed that the difference between ?N/?S estimated for genes with high and low expression levels was significantly smaller for M. m. musculus compared to that observed for M. m. castaneus The difference between the ?N/?S of broadly expressed and tissue specific genes was much higher for M. m. castaneus compared to that of M. m. musculus. Furthermore, the difference between the ?N/?S computed for essential and non-essential genes was much smaller for M. m. musculus than M. m. castaneus A similar pattern was observed for genes involved in many protein-protein interactions versus those involved in one. These results suggest that the effects of the determinants on protein evolution were much reduced for the population with small Ne due to increased genetic drift.

SUBMITTER: Subramanian S

PROVIDER: S-EPMC6083237 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Effect of genetic drift on determinants of protein evolution.

Subramanian Sankar S

Biology letters 20180701 7

A number of previous studies reported that gene expression, tissue specificity, gene essentiality and the number of protein-protein interactions influence the rate of protein evolution. Here we investigated the influence of effective population size (Ne) on these determinants of protein evolution. For this purpose, we compared the ratio of non-synonymous-to-synonymous diversities (πN/πS) estimated for protein-coding genes of Mus musculus c ...[more]

PMID: 30021860

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Project description:Proteins from thermophiles are generally more thermostable than their mesophilic homologs, but little is known about the evolutionary process driving these differences. Here we attempt to understand how the diverse thermostabilities of bacterial ribonuclease H1 (RNH) proteins evolved. RNH proteins from Thermus thermophilus (ttRNH) and Escherichia coli (ecRNH) share similar structures but differ in melting temperature (T(m)) by 20 °C. ttRNH's greater stability is caused in part by the presence of residual structure in the unfolded state, which results in a low heat capacity of unfolding (ΔCp) relative to ecRNH. We first characterized RNH proteins from a variety of extant bacteria and found that Tm correlates with the species' growth temperatures, consistent with environmental selection for stability. We then used ancestral sequence reconstruction to statistically infer evolutionary intermediates along lineages leading to ecRNH and ttRNH from their common ancestor, which existed approximately 3 billion years ago. Finally, we synthesized and experimentally characterized these intermediates. The shared ancestor has a melting temperature between those of ttRNH and ecRNH; the T(m)s of intermediate ancestors along the ttRNH lineage increased gradually over time, while the ecRNH lineage exhibited an abrupt drop in Tm followed by relatively little change. To determine whether the underlying mechanisms for thermostability correlate with the changes in T(m), we measured the thermodynamic basis for stabilization--ΔCp and other thermodynamic parameters--for each of the ancestors. We observed that, while the T(m) changes smoothly, the mechanistic basis for stability fluctuates over evolutionary time. Thus, even while overall stability appears to be strongly driven by selection, the proteins explored a wide variety of mechanisms of stabilization, a phenomenon we call "thermodynamic system drift." This suggests that even on lineages with strong selection to increase stability, proteins have wide latitude to explore sequence space, generating biophysical diversity and potentially opening new evolutionary pathways.

Project description:BACKGROUND: The highly pathogenic H5N1 is a major avian pathogen that intensively affects the poultry industry in Egypt even in spite of the adoption of vaccination strategy. Antigenic drift is among the strategies the influenza virus uses to escape the immune system that might develop due to the pressure of extensive vaccination. H5N1 mutates in an intensified manner and is considered a potential candidate for the possible next pandemic with all the catastrophic consequences such an eventuality will entail. METHODS: H5N1 was isolated from the pooled organ samples of four different affected flocks in specific pathogen free embryonated chicken eggs (SPF-ECE). A reverse transcriptase polymerase chain reaction (RT-PCR) was performed to the haemagglutingin and neuraminidase. Sequencing of the full length haemagglutingin was performed. Sequence analyses of the isolated strains were performed and compared to all available H5N1 from Egyptian human and avian strains in the flu database. Changes in the different amino acid that may be related to virus virulence, receptor affinity and epitope configuration were assigned and matched with all available Egyptian strains in the flu database. RESULTS: One out of the four strains was found to be related to the B2 Egyptian lineage, 2 were related to A1 lineage and the 4th was related to A2 lineage. Comparing data obtained from the current study by other available Egyptian H5N1 sequences remarkably demonstrates that amino acid changes in the immune escape variants are remarkably restricted to a limited number of locations on the HA molecule during antigenic drift. Molecular diversity in the HA gene, in relevance to different epitopes, were not found to follow a regular trend, suggesting abrupt cumulative sequence mutations. However a number of amino acids were found to be subjected to high mutation pressure. CONCLUSION: The current data provides a comprehensive view of HA gene evolution among H5N1 subtype viruses in Egypt. Egyptian H5N1-AIVs are constantly undergoing genetic changes and reveal a complex pattern of drifts. These findings raise the concerns about the value of using influenza vaccines in correlation with the development of antigenic drift in influenza epidemics.

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Effect of genetic drift on determinants of protein evolution.

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Effect of genetic drift on determinants of protein evolution.

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