A Triad Of Flexibility, Adaptability And Plasticity
Opinions on topical issues from thought leaders, columnists and editors.
Dr Prameela Kannan Kutty
It’s all about adaptability when dealing with the interactions of microbes, genes and natural selection.
“Mutation” is a commanding term in the dynamic life cycle of species. It implies how a gene, at the very core of human existence, is modified in a manner that alters its signals with impact passed down generations.
Far from portraying bizzare metamorphosis, a mutation is an important event in dynamic variation, facilitating diversity and optimal adaptability in dimensions of space.
Microbes and genetic diversity
Mutations allow random alterations to be dealt with by the plasticity of choices made by a mature universe.
It may seem somewhat strange, but of interest, to note that microbes that cause diseases have contributed to facets of genetic variation and that human populations thrive on principles of evolution.
When a disease afflicts large numbers of people, the process of natural selection increases the possibility that genes that are more resistant against the disease are nurtured.
Karlsson et al (Nat Rev Genet, 2014) allude to “signatures of selection” that differ with age, geography and the level of danger of the microbe. Population traits are driven by the nature of diseases caused by microbes, and this is more evident in long-lasting infections. Microbes that cause chronic infections such as malaria, tuberculosis, leprosy or acquired immunodeficiency syndrome (AIDS) are likely to strongly influence natural selection because these diseases are not only debilitating, but also restrict growth, development and intellect with direct or indirect impairment of reproductive potential.
Chronic endemic diseases in a population have naturally allowed certain genes that are “heterozygous” (hence not lethal or disease causing) to be naturally selected over others.
Healthy carriers of the sickle cell gene are resistant to malaria, and this is protective in malaria-endemic regions where the disease impacts life and well-being.
The interaction between genes and diseases is also seen in specific geographic regions where resistance to certain infections occur in some genetic diseases. Examples of this are resistance to cholera toxin in carriers of cystic fibrosis or possible selective protection against tuberculosis in a rare genetic disorder.
Mutations and viruses
In viral infections, mutations occur due to copying defects during replication and may be consequential.
A virus has its replication at the heart of events. It enters a cell, sabotages and reprogrammes host cell machinery, “uncoats”, releasing genome and blue print for its progeny. Then it replicates, producing new virions, assembled and released through demolition of the infected cell or by acquiring specks of viral envelope.
Some viruses, especially the ribonucleic acid (RNA) viruses (unlike many deoxyribonucleic acid (DNA) viruses), are inclined to copying errors. If copying changes are merged into the viral genome, chockfull with hereditary data and viral codes, it will climax in a viral mutation.
Indiscriminate as it were, a mutation may turn out to be either risky, beneficial or without consequence to the virus. Mutation rates mirror the likelihood that gene changes are passed to the next generation of viruses. However, very hazardous mutations are acted upon by the silent principles underlying natural selection in viral evolution.
Viral mutations shed some light on virus hops from host-to- host and spill-overs from animal to human realm, triggering horrific pandemics.
Although much is yet to be determined in COVID-19, a viral tracking tool such as the sequence analyses implies that corona viruses transform relatively slowly compared to other RNA viruses. Proof reading enzymes that correct mega-copying mistakes may explain this.
Yet, to date, thousands of mutations occur possibly without great consequences, with exception to the spike protein mutation which tends to increase infectivity.
Immune evasion, as with the influenza A virus respiratory infection, can delay recovery from the illness, boost human-to-human transmission and set off seasonal epidemics.
In more chronic viral infections, viral mutations elucidate certain drug-resistance patterns with multiple combination regimes in HIV treatment. In hepatitis B, a DNA virus, mutations may impact the risk of liver cancer and vaccination responses.
Versatile viral adaptation by mutation facilitates disease transmission risk. The chikungunya virus illustrates this by adaptation to a novel mosquito vector, the Aedes albopictus, in addition to the more common Aedes aegypti. (WHO, CDC)
Mutation can also impinge on vaccination responses. The call for repeated flu shots for each flu season is due to influenza viruses modifying outer surface proteins, referred to as “antigenic drift”. This may make it appear poles apart to the immune system, rendering antibodies already present against one strain ineffective against another.
Some mutations can also work optimistically and could reduce disease impact, and these strains could be helpful in vaccine development. Advances in technology support comprehensive viral sequencing towards this.
Human genes are intertwined with the genetics of microbes and the variables of the environment for adaptation and enhanced survival. Population characteristics are sometimes cherry picked to adapt to unique environments for greater human resilience.
Viral mutations clarify disease patterns, environmental adaptation and treatment trends. There is often a trade-off to infection spread and viral virulence by the tenets of natural selection.
The triad of genes, microbes and nature’s choices reflects endless possibilities in an ever-changing universe.
Dr Prameela Kannan Kutty is Professor of Paediatrics at Universiti Pertahanan Nasional Malaysia.
(The views expressed in this article are those of the author and do not reflect the official policy or position of BERNAMA)