Posts Tagged ‘Darwinian evolution’

Finch character displacement

Larry H. Bernstein, MD, FCAP



Genetic Study of Darwin’s Finches Catches Evolution in Action



The medium ground finch (Geospiza fortis), shown here, diverged in beak size from the large ground finch (Geospiza magnirostris) on Daphne Major Island, Galápagos following a severe drought. Genomic screening of the genomes of medium ground finches revealed that a particular gene, HMGA2, played a large role in the rapid evolution of a smaller overall beak size in the medium ground finch. [Peter R. Grant]

An evolutionary phenomenon first described by Charles Darwin has the support of new and unusually strong supporting evidence. The phenomenon, called character displacement, may occur when species compete for the same food source. The species may evolve different body shapes, such as different beak sizes in the case of finches, diverging from each other until they relieve competitive stress.

Darwin developed the idea of character displacement after observing the finches of the Galápagos Islands. He proposed that changes in the size and form of the beak have enabled different species to utilize different food resources, such as insects, seeds, and nectar from cactus flowers, as well as blood from seabirds.

In a study of character displacement among Darwin’s finches, researchers from Uppsala University and Princeton University have now identified a gene that explains variation in beak size within and among species. The gene contributed to a rapid shift in beak size of the medium ground finch following a severe drought.

The details of the study appeared April 22 in the journal Science, in an article entitled, “A Beak Size Locus in Darwin’s Finches Facilitated Character Displacement during a Drought.” The article describes how the researchers alighted on a gene called HMGA2 after screening the genomes of medium ground finches that survived or died during a drought that occurred between 2004 and 2005. The researchers found that the HMGA2 gene comes in two forms: one is common in finches with small beaks, whereas the other is common in finches with large beaks. The proportion of the two forms in the birds’ genome changed as a result of the better survival of birds with small beaks.

“We used genomic analysis to investigate the genetic basis of a documented character displacement event in Darwin’s finches on Daphne Major in the Galápagos Islands,” wrote the authors. “We discovered a genomic region containing the HMGA2 gene that varies systematically among Darwin’s finch species with different beak sizes. Two haplotypes that diverged early in the radiation were involved in the character displacement event.”

In a previous study from the same team, the ALX1 gene was revealed to control beak shape (pointed or blunt). The HMGA gene that figures in the current study was previously associated with variation in body size in dogs and horses, and it is one of the genes that show the most consistent association with variation in stature in humans, a trait that is affected by hundreds of genes. HMGA2 has also a role in cancer biology as it affects the epithelial–mesenchymal transition (EMT) that is important for metastasis and cancer progression.

“Our data show that beak morphology is affected by many genes, as is the case for most biological traits,” said Sangeet Lamichhaney, the current study’s first author and a doctoral student in the laboratory of Leif Andersson, one of the study’s senior authors and a genomics professor at Uppsala. “However, we are convinced that we now have identified the two loci with the largest individual effects that have shaped the evolution of beak morphology among the Darwin’s finches.”

Andersson collaborated with Princeton researchers Peter Grant, the Class of 1877 Professor of Zoology, Emeritus, and B. Rosemary Grant, a senior research biologist, emeritus, in ecology and evolutionary biology.

“It was an exceptionally strong natural-selection event,” noted Peter Grant, who pointed out that that because Daphne Major is in an entirely natural state, the occurrence was completely unaffected by humans. “Now we have demonstrated that HMGA2 played a critical role in this evolutionary shift and that the natural selection acting on this gene during the drought is one of the highest yet recorded in nature.”

“This research tells us that a complex trait such as beak size can evolve significantly in a short time when the environment is stressful,” Rosemary Grant added. “We know that bacteria can evolve very quickly in the lab, but it is quite unusual to find a strong evolutionary change in a short time in a vertebrate animal.”


Linked loci and Galapagos finch size

Observations of parallel evolution in the finches of the Galapagos, including body and beak size, contributed to Darwin’s theories. Lamichhaney et al. carried out whole-genome sequencing of 60 Darwin’s finches. These included small, medium, and large ground finches as well as small, medium, and large tree finches. A genomic region containing the HMGA2 gene correlated strongly with beak size across different species. This locus appears to have played a role in beak diversification throughout the radiation of Darwin’s finches.

Science, this issue p. 470

Ecological character displacement is a process of morphological divergence that reduces competition for limited resources. We used genomic analysis to investigate the genetic basis of a documented character displacement event in Darwin’s finches on Daphne Major in the Galápagos Islands: The medium ground finch diverged from its competitor, the large ground finch, during a severe drought. We discovered a genomic region containing the HMGA2 gene that varies systematically among Darwin’s finch species with different beak sizes. Two haplotypes that diverged early in the radiation were involved in the character displacement event: Genotypes associated with large beak size were at a strong selective disadvantage in medium ground finches (selection coefficient s = 0.59). Thus, a major locus has apparently facilitated a rapid ecological diversification in the adaptive radiation of Darwin’s finches.


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Tumor Progression

Larry H. Bernstein, MD, FCAP, Curator



GEN News Highlights Nov 10, 2015   Darwinian Selection Does Not Influence Tumor Progression



New answers may have just emerged in a long-standing debate in the field of oncology and molecular evolution. The neutral theory of molecular evolution states that changes occurring at the molecular level are not caused by natural selection, but rather by the random genetic drift of mutant alleles. In contrast, Darwinian selection adheres to the idea that a molecular mutation holds some selective advantage over the wild-type, allowing it to thrive.

When viewing these two theories through the lens of carcinogenesis, it is not difficult to envision the applicability of either theory. However now, new evidence from scientists at the University of Chicago and the Beijing Institute of Genomics may tip the scales in favor of neutral theory. This collaborative scientific effort assembled data from one of the most rigorous genetic sequencing ever carried out on a single tumor—revealing a much greater level of genetic diversity than expected.

The investigators excised a tumor roughly 3.5 centimeters in diameter (slightly smaller than a ping-pong ball), from a hepatocellular carcinoma tumor of the liver. The research team estimated that the tumor contained more than 100 million distinct mutations within genetic coding regions, which is thousands of times more than they anticipated. The impact of this finding is that even microscopic tumors are likely to contain extremely high genetic diversity and with so much variation there are likely many cells contained within able to resist standard post-surgical cancer treatment such as chemotherapy and radiation.

“With 100 million mutations, each capable of altering a protein in some way, there is a high probability that a significant minority of tumor cells will survive, even after aggressive treatment,” explained study director Chung-I Wu, Ph.D., professor of ecology and evolution at the University of Chicago. “In a setting with so much diversity, those cells could multiply to form new tumors, which would be resistant to standard treatments.”

The findings from this study were published recently in PNAS through an article entitled “Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution.”


Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution

Shaoping Linga,1Zheng Hua,1Zuyu Yanga,1Fang Yanga,1Yawei LiaPei LinbKe ChenaLili DongaLihua CaoaYong Taoa , et al.
PNAS Nov 11, 2015,              http://dx.doi.org:/10.1073/pnas.1519556112


A tumor comprising many cells can be compared to a natural population with many individuals. The amount of genetic diversity reflects how it has evolved and can influence its future evolution. We evaluated a single tumor by sequencing or genotyping nearly 300 regions from the tumor. When the data were analyzed by modern population genetic theory, we estimated more than 100 million coding region mutations in this unexceptional tumor. The extreme genetic diversity implies evolution under the non-Darwinian mode. In contrast, under the prevailing view of Darwinian selection, the genetic diversity would be orders of magnitude lower. Because genetic diversity accrues rapidly, a high probability of drug resistance should be heeded, even in the treatment of microscopic tumors.


The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. Here, from a hepatocellular carcinoma (HCC) tumor, we evaluated multiregional samples from the tumor, using either whole-exome sequencing (WES) (n = 23 samples) or genotyping (n = 286) under both the infinite-site and infinite-allele models of population genetics. In addition to the many single-nucleotide variations (SNVs) present in all samples, there were 35 “polymorphic” SNVs among samples. High genetic diversity was evident as the 23 WES samples defined 20 unique cell clones. With all 286 samples genotyped, clonal diversity agreed well with the non-Darwinian model with no evidence of positive Darwinian selection. Under the non-Darwinian model,MALL (the number of coding region mutations in the entire tumor) was estimated to be greater than 100 million in this tumor. DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non-Darwinian evolution should be heeded in cancer treatments even for microscopic tumors.

intratumor heterogeneity  genetic diversity  neutral evolution  cancer evolution  natural selection

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1519556112/-/DCSupplemental.


Scientists at the Beijing Institute of Genomics sampled nearly 300 regions from one slice of the hepatocellular tumor and sequenced or genotyped each one searching for genetic changes. Once they analyzed their data and applied a modern population genetic theory, their results lead them to the 100 million coding-region mutation estimate for the whole tumor.

This extensive level of heterogeneity within a single tumor, which is way beyond what a Darwinian process would permit, makes the selectionism vs. neutralism debate of the 1980s “suddenly medically relevant,” Dr. Wu remarked. Since previous to the current study, no one had ever genetically dissected a tumor as thoroughly, the commonly held theory was that tumors had from a few hundred up to 20,000 genetic alterations that were not present in the patient’s healthy cells.

“Our study is the non-Darwinian process writ small, down to the cellular level,” Dr. Wu noted. “In the Darwinian struggle, there are—from the tumor’s point of view—few beneficial mutations, meaning changes that give tumor cells a growth advantage. When there are no such limits on genetic variation, however, mutations can emerge and apparently thrive.”

“This could potentially change how we think about tumor growth and spread, but the direct clinical implications of this study may not be obvious on the surface,” added co-author Daniel Catenacci, M.D., assistant professor and medical oncologist at the University of Chicago.

While the bulk of the mutations were at very low frequencies, drug intervention could provide some of the genetic mutations with a progression path forward.

“The presence of so many random mutations could present a problem to specifically targeted therapies,” Dr. Catenacci stated. “It almost guarantees that some cells will be resistant. But it also suggests that aggressive treatment could push tumor cells into a more Darwinian mode.”

Since the current study only focused on a single tumor type, it remains to be seen how comparable this data will be for other types of cancerous tumors. However, regardless of narrow focus, the results from this analysis raises important question about tumor evolution and heterogeneity.



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