Evolution of cancer occurs in bursts(?) of evolution or gradual(?) evolution …..

Aneuploidy (abnormal numbers of chromosomes, transposition of segments, and duplicated chromosomes, even in cells adjacent to one another) is a hallmark of many different types of cancer. However, knowledge of how these complex genomic rearrangements evolve during tumorigenesis is still largely not understood.

In this publication [see attached article & editorial], authors developed a highly multiplexed single-nucleus sequencing method to investigate copy number evolution in patients with triple-negative breast cancer. [“Triple-negative” means the tumor is estrogen receptor (ESR1)-negative, progesterone receptor (PGR)-negative and HER2 (ERRB2 receptor tyrosine kinase)-negative. The good news is that this type of breast cancer typically responds favorably to chemotherapy.]

Authors sequenced 1,000 single cells from tumors in 12 patients and identified one to three major clonal subpopulations in each tumor that shared a common evolutionary lineage. For each tumor, they also identified a minor subpopulation of non-clonal cells that were classified as “metastable” or “pseudo-diploid”. Phylogenetic analysis and mathematical modeling suggested these data are unlikely to be explained by a gradual accumulation of copy number events over time. In contrast, these data challenge the paradigm of gradual evolution––showing that the majority of copy number aberrations are acquired at the earliest stages of tumor evolution, by way of short punctuated bursts [this is what’s called saltationism; see? I learned a new word today], followed by stable clonal expansions that subsequently form the tumor mass.

This model challenges both Darwinian principles: if copy number changes happen in bursts, then there is no gradual accumulation and, if all clones are established early on, then the selec­tive advantages of later mutations have only a marginal role in cancer evolution. [But it seems reasonable to postulate that both Darwinian and saltationism play different distinct roles during evolution.] This model [in present attached article] is very similar to the recently proposed “Big Bang model” in colon cancer. Moreover, this work joins previous studies that ques­tioned the Darwinian model by highlighting the importance of neutral evolution or massive non-gradual genomic events.

It should be emphasized that these discoveries were not possible until it became feasible to perform single-cell whole-genome sequencing.

Also, the development of a tumor is not that different from other evolutionary/developmental processes. If cells are always highly plastic, i.e. subject to quick adaptive changes when challenged with danger (anything that might kill or damage the organism, tumor, or bacterial colony), then the organism-tumor-bacterial colony uses such an adaptive advantage to “survive to live another day” in the face of changing environmental adversity.

Nat Genet   Oct 2o16; 48: 119–130 (Article)  and  pp 1102-1103 (News-N-Views)


Dear Glenn Begley and Olavi Pelkonen,


Yes, the “Cambrian Explosion” refers to the (evolutionarily “very sudden”) appearance in the fossil record of most major animal body plans ~542 million years ago, with so many new fossils appearing during in an interval of perhaps 20 million years or less. On an evolutionary time-scale, 20 million years is a “rapid burst”, which would appear to be inconsistent with Darwin’s proposed very gradual rate of evolutionary changes. It seems reasonable that both Darwinian “gradual” and saltatory “explosive” evolution––can occur at distinctly different times during evolution, and none of this detracts from Darwin’s original observations.


So, yes, the Cambrian Explosion would be considered a saltatory event, and rapid changes like the Cambrian Explosion are know to have appeared at other times in the fossil record––often following times of major extinction, caused in many cases by dramatic global climate changes.


The Cambrian Explosion presents a number of interesting and important research questions. It now seems likely that gene families determining head vs tail, dorsal vs ventral, and left- vs right-handedness appeared during the Cambrian Explosion. And that these genes rapidly duplicated (gene-duplication events) because it benefitted the animal in its fight for survival against environmental adversity. Thus, symmetrical animals such as sponge and jellyfish before the Cambrian Explosion evolved into ancestral soft-bodied precursors of conch, mollusk and worm after the Cambrian Explosion.

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