The relevance of sequence conservation in molecular biology cannot be disputed. Ever since the pioneering work of Linus Pauling and Emile Zuckerkandl in the early 60’s, it has been the driving force behind numerous discoveries. By the mid-60’s, Margaret Dayhoff was already leveraging computers to draw links between sequence similarity and evolutionary relationships while her Protein Atlas introduced the concept of gene families.
In the more than 50 years since that time, scores of amino acid and nucleic acid sequences with various degrees of conservation among numerous organisms and viruses have been linked to fundamental pathways. Discoveries over the last 20 years have revealed striking instances of conservation in organisms separated by hundreds of millions of years of evolution.
Characteristic examples include the let-7 family of the regulatory non-coding molecules known as microRNAs (miRNAs) that is conserved from worms to humans, and the tumor suppressor gene known as TP53 that is known to have 40 copies in elephants, a species resistant to the development of cancer. Perhaps not surprisingly, when such conserved sequences are either deleted or altered then disease sets in.
Discoveries over the last 20 years have revealed striking instances of conservation in organisms separated by hundreds of millions of years of evolution.
For a long time, the deviations from this scientific paradigm were infrequent. In fact, the counter-examples that appeared in the literature were so rare that biologists, geneticists, and clinicians used this observation as an argument in support of the conservation rule. Perhaps the best known early example of an important molecule that was not conserved is XIST. Such had been the hold of sequence conservation in researchers’ thinking that conservation was soon assumed to be not only sufficient but necessary as well.
As shotgun sequencing became the norm in the late-90’s, more genomic sequences became available thereby…