Review: The Making of the Fittest


Just as fossils provide a window into the past, evolution leaves a footprint on DNA. In The Making of the Fittest, Sean Carroll explains some of the overwhelming evidence for evolution provided in DNA, bringing to life new examples from sequences of DNA that once coded for genes no longer used, remnants of ancestral lives, and evidence of evolutionary change. As Carroll explains, "every evolutionary change between species, from physical form to digestive metabolism, is due to — and recorded in — changes in DNA" (p 14). Using this forensic evidence of evolution, Carroll reveals how these relics provide new "sources of insights into traits and capabilities that have been abandoned as species evolved new lifestyles" (p 16). Carroll also deals a blow to the claim that evolution occurs completely at random, and that order and complexity of nature are surely outside the realm of random processes. The descriptions offered in The Making of the Fittest provide powerful examples of how evolution actually works, and why evolution matters. A few are discussed below, but definitely read The Making of the Fittest, and evaluate the data for yourself.


Carroll's first example, of bloodless fishes in the Antarctic, shows the wonderful way science operates. An unconfirmed observation of bloodless fishes living in the cold waters of the Antarctic challenged the working hypothesis that all vertebrates must have red blood cells, contingent on their requirement for the oxygen-carrying molecule hemoglobin. Years passed, with no verification of these strange fish. However, eventual proof of the actual existence of bloodless fishes — which turned out in fact to have blood that lacked red blood cells and hemoglobin — then fueled more empirical work. Scientific research, in the form of actual observations, data, and facts, provided an explanation of how these fishes came to exist without hemoglobin, in a story that is a much more awesome and compelling than any just-so story that could be written.

The evolutionary explanation, described by Carroll, shows, in uncontestable detail, how bloodless icefish have evolved in response to "opportunity and necessity". This evolutionary narrative takes place over the past 55 million years, during which temperatures of the Antarctic Ocean have dropped, from about 20° C to less than 0° C in some locales. A cold environment presents challenges to living organisms, which have to adapt in response: for example, since fluids like blood move much more slowly in colder temperature, animals in such environments compensate by evolving less viscous blood and/or increasing the surface area for oxygen exchange.

The protagonists of our evolutionary narrative are fishes of the teleost suborder Notothenioidei, commonly known as icefish, which dominate the fish fauna of the freezing coastal regions of the Southern Ocean. Notothenioid fishes in the Antarctic have either much lower hematocrit percentages (that is, a lower percentage of red blood cells in their blood) or no hemoglobin-containing red blood cells in their blood (and are therefore considered bloodless). The bloodless icefish have relatively large gills and scaleless skin with unusually large capillaries. Modifications in the heart and gills facilitate the transfer of oxygen from water to tissue. Icefish also synthesize antifreeze glycoproteins (AFGP1–AFGP8) that inhibit growth of ice crystals and therefore prevent freezing of tissues.

Enter DNA ... providing a window into the past and evidence of change. Bloodless icefish in the Antarctic have genes for hemoglobin, but the genes have accumulated mutations, and are now functionless. The presence of relict hemoglobin genes points to an ancestral way of life, no longer followed by the fish, and provides evidence for descent with modification. Moreover, the DNA sequence of the antifreeze glycoprotein (AFGP) informs us how the evolutionary change occurred. The notothenioid AFGPs (a family of at least eight different isoforms — various forms of the same protein) are composed of a simple glycotripeptide repeat, (Thr-Ala/Pro-Ala)n, with the disaccharide galactose-N-acytylglactosamine attached to each Thr, and the dipeptide Ala-Ala at the N terminus (Chen and others 1997). The smallest AFGP isoform consists of four repeats; the largest of 55 repeats. Variation abounds among these isoforms, and AFGP polyprotein precursors contain various combinations of these isoforms. Additionally, there are multiple genes and multiple AFGP copies per gene, which contribute to high levels of circulating proteins and suggest extensive duplications gave rise to this protein family (Chen and others 1997).

The first AFGP gene characterized was from the Antarctic notothenioid Notothenia coriiceps (Hsiao and others 1990), and a search of Genbank found that the 3' flanking sequence of the Notothenia coriiceps AFGP gene, starting from the termination codon to about 100 nucleotides downstream, to be about 80% identical to the coding sequence of the C terminus (50 residues) of the trypsinogen cDNA of Atlantic plaice, providing a potential pathway for evolution of the antifreeze protein from a digestive protein. Analysis of both the AFGP gene and the trypsinogen gene from the giant Antarctic notothenioid Dissocstichus mawsoni showed 4–7% sequence divergence (Chen and others 1997). And, as can only be predicted and tested within an evolutionary framework, a transcriptionally active chimeric gene that encodes both the AFGP polyprotein and the trypsinogen protease was found (Cheng and Chen 1999). Evolution works "by tinkering with materials that are available — in this case a little piece of another gene's code — rather than by designing new things completely from scratch" (p 26). The Making of the Fittest is full of similar descriptions of evolution in action. Mutation, heritable variation, and differential survival in a changing environment provide an explanation of evolutionary change that is overwhelmingly consistent with, and supported by, our observations across all major groups of organisms.


A common misconception about evolution is that it proceeds by random chance, and many creationists use this myth to discredit evolution. Carroll dismisses this misconception, offering a clear and understandable description of the mathematical power of evolution to produce change. Carroll uses everyday examples — winning the lottery, dying in various kinds of accidents, and saving money — to address commonly held misconceptions about the probability of evolution, specifically the potential for random events to generate complexity and the ability of selection to cause significant change. Critics of evolution want people to believe that mutations cannot lead to new information. Carroll clearly shows where these arguments fall apart. He first points out that while mutations are random, selection determines what chance occurrences are retained." Given enough time identical or equivalent mutations will arise repeatedly by chance and their fate (preservation or elimination) will be determined by the conditions of selection upon the traits they affect" (p 155). Carroll also draws an analogy between the power of natural selection and that of compounding interest, explaining that "small differences among individuals, when compounded by natural selection over time, really do add up to the large differences we see among species" (p 43). Understanding the power of selection as an analogy to the practice of compounding interest could better prepare everyone for an age of global climate change as well as a global economy.


Carroll states, quite rightly, that "DNA decisively confirms [Darwin's] picture of evolution" (p 16), and shows how molecular data continue to inform our understanding of how natural selection operates as a mechanism of evolutionary change in his discussions of the distribution of color vision and olfactory sensitivity in groups of mammals, population responses to environmental change, microbial resistance to antibiotics, and sicklecell trait in humans. Expecting natural selection to explain all evolutionary change, however, would be terribly near-sighted, ignoring much of the results of research in evolutionary biology, population genetics, and molecular biology over the last 150 years. Development, mutation, gene duplication, gene rearrangement, and genetic drift must be incorporated into a complete understanding of evolutionary change.

Carroll has two other books (Carroll and others 2001; Carroll 2005) that address some of these topics in more depth. It is unfortunate that, in a time when evolutionary biology forms the backbone of so much research into medical advances and provides a greater understanding of the genetic components of human health and disease, Carroll felt the need to include a chapter on discussing creationism, including "intelligent design". The chapter is, however, sadly needed, as antievolution groups continue to undermine sound science education. Critics of evolution continually disregard the predictive power of evolutionary explanations, which, as Carroll clearly shows, explain how icefish evolved from ancestors with the capacity to synthesize hemoglobin, later lost as they adapted to living in freezing cold water. To be sure, those voicing dissent will not be satisfied until every nucleotide substitution and gene duplication event is historically identified and mapped, and in the interval will insist that we reject the entire evolutionary explanation in favor of a supernatural explanation with no evidence at all. Believing that the adaptations of icefish were designed by an intelligent agency is about as scientific, and intellectually satisfying, as Kipling's explanation of how the leopard got its spots.

The scientific evidence for evolution provided by Carroll will probably not enlighten those who refuse to accept the nature of scientific investigation and oppose Darwinian evolution. But The Making of the Fittest should be required reading for those teetering on the edge of accepting evolution, as well as anyone interested in learning more about the great epic of life. Its appeal to a wide audience also makes the book of great value to teachers who can mine the text — available in a quite affordable paperback version, happily — for opportunities to teach students about the nature of science and fresh and exciting examples of how evolution works.



Carroll SB. 2005. Endless Forms Most Beautiful: The New Science of Evo Devo. New York: WW Norton.

Carroll SB, Grenier JK, Weatherbee SD. 2001. From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design. Malden (MA): Blackwell.

Chen L, DeVries AL, Cheng C-HC. 1997. Evolution of antifreeze glycoprotein gene from a trypsinogen gene in Antarctic nothenioid fish. Proceedings of the National Academy of Science USA 94: 3811–6.

Cheng C-HC, Chen L. 1999. Evolution of an antifreeze glycoprotein. Nature 410: 443–4.

Hsiao KC, Cheng C-HC, Fernandes IE, Detrich HW, DeVries AL. 1990. An antifreeze glycopeptide gene from the Antarctic Cod Notothenia coriiceps neglecta encodes a polyprotein of high peptide copy number. Proceedings of the National Academy of Science USA 87: 9265–9.

About the Author(s): 

Louise S Mead
PO Box 9477
Berkeley CA 94709-0477

Louise S Mead is NCSE's Education Project Director

The Making of the Fittest: DNA and the Ultimate Forensic Record of Evolution
Louise S Mead
Sean B Carroll
This version might differ slightly from the print publication.
New York: WW Norton, 2006 (paperback 2007). 288 pages.