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Department of Ecology and Evolutionary Biology, University of California, Irvine, California, USA
1 Correspondence: Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697, USA. E-mail: fjayala{at}uci.edu
"Gene sharing" means, according to Joram Piatigorsky in this engrossing book, that "one gene produces a polypeptide that has more than one molecular function: two or more entirely different functions of a polypeptide share the identical gene (1)
." The key point rests with "one polypeptide," not just "one gene" having two different functions. A given gene may have multiple functions as a consequence of differential splicing, gene duplication, or otherwise. The concept of gene sharing was, however, introduced to account for the observation that crystallins, structural proteins that account for the transparent and refractive properties of the eye’s lens, also perform metabolic functions and non-refractive, stress-related functions in other tissues.
Another key element of the notion of gene sharing is that the molecular functions of the polypeptide are different, and not simply that a given specific function has different phenotypic consequences. "Specialization of an individual protein neither fixes its functional boundaries in a molecular sense nor prevents it from changing functions under different circumstances (2)
." After the early discovery that crystallins perform non-refractive metabolic functions in tissues other than the eye, Piatigorsky became gradually convinced that the use of the same protein for different functions is widespread. This was the motivation to write this book. "I believe that the extensiveness of gene sharing and protein multifunctionality argues against rigid compartmentalization in biology, and introduces a fluid concept of genes and proteins (3)
." It does, indeed, and it contributes significantly to expand the notion of the "gene" and has important consequences in evolution.
It was discovered in the late 1980s that crystallins were identical, not just similar, to enzymes performing functions unrelated to vision and in tissues other that those in the eye. Duck 
-crystalline turned out to be identical to lactate dehydrogenase B4, the 
-crystalline of chicken was the same as argininosuccinate lyase, and the turtle 
-crystalline was identical to 
-enolase. The observation of the identity, not just similarity or homology, of crystalline and enzyme was critical. The same major water-soluble structural protein was expressed at lower levels in other tissues of the same animal, where it performed non-refractive, enzymatic roles. "It is now known that numerous, perhaps all, families of proteins that function as lens crystallines fit neatly into this story of evolution by a gene-sharing process (4)
."
Gene Sharing and Evolution exhibits an effective dialectic. After arguing persuasively with sustained evidence for the likely universality of the double function—one structural, the other enzymatic—of the crystalline proteins, Piatigorsky asserts, first somewhat tamely, that crystallines are but one example of proteins having different tissue-specific functions or serving multiple roles in the same tissue. Then, he adds: "Review of the scientific literature makes it clear that protein multifunctionality is more the rule than the exception of protein behavior (5)
." He is persuaded that persistent investigations are likely to show that "Perhaps all proteins perform many different functions by employing as many different mechanisms...The versatility of proteins challenges us to discover the full range of a protein’s function rather than attempt to fit its expected function" within a framework derived "from past experiences." He adds, "This is especially important in evolution where orthologous proteins differ in cellular environment, gene expression, and amino acid sequence. The bewildering array of functions performed by each individual protein within and between species testifies to the endless rich pragmatism and imagination of Nature (6)
." This is a forcefully stated argument of great consequence, which perhaps justifies the personification stated, although obviously only metaphorically meant, in the last seven words of the statement.
Piatigorsky points out that there is a great variety of functional differences performed by an individual polypeptide, such as nucleotide metabolism and lipid secretion; redox control and eyespot morphogenesis; and circulating carrier protein and liver-detoxifying enzyme. He reviews in some detail a number of instances well-substantiated in the published literature (7)
: glycolytic enzymes and versatile hexokinases; citrate synthase, which serves as enzyme and as cytoskeletal structure; lactate dehydrogenase, "an enzyme for all seasons;" enolase, "another versatile protein;" xanthine dehydrogenase, enzyme as well as envelope; serum albumin, which functions as transport protein, enzymatic vasodilator, and detoxifier; cytochrome c, with roles in electron transport, cell death, and light filtration; and still more instances. The relevant literature is reviewed and critically evaluated in each instance. Informative and effectively didactic summarizing illustrations are used in several cases, such as lactate dehydrogenase, with arrows pointing to five different functions, some in different organisms and some of the five functions extending to additional ones in each of the five categories; and such as enolase, with arrows pointing out to its ubiquitous function as a glycolytic enzyme, its role in the bovine central nervous system, its function as an actin-binding protein, and five more roles in different tissues or organisms.
Piatigorsky argues, as pointed out above, for a strict notion of gene sharing, namely, a given polypeptide having different functions in different tissues, often due to different levels of expression, but also as a consequence of being expressed in different cellular environments, and otherwise. Thus, he excludes from the concept of gene-sharing phenomena that may have some similarity, such as gene duplication with subfunctionalization (think of alpha, beta, and other hemoglobin chains); polypeptides resulting from different gene splicing; identical functions resulting in different phenotypes; pleiotropy, which "refers more to having single genes control multiple traits" and thus "is more closely connected to phenotype than to protein function per se (8)
." Helpfully, he dedicates one full chapter to the "elusive concept" of the gene, starting with the early notion of a gene as a factor located within a chromosome and reaching into the molecular era of "so much data, so many possibilities," where "the concept and precise boundaries of a gene remain ambiguous even [at] present (9)
." Gene sharing is just one more of the multidimensional facets of the gene concept.
Particularly interesting to this reviewer is Piatigorsky’s enlightened discussion of the molecular clock. He reviews my analysis of the "disquieting" changes in rate of evolution through time of two particular genes, Gpdh and Sod, in Drosophila. "The clocks tick in opposite directions for these two enzymes." As he summarizes it, "10 amino acid replacements occurred in the Sod gene during the last 75 million years, although only 21 replacements occurred in the previous 600 million years." On the contrary, "the Gpdh gene has evolved slowly (1.1 x 10–10 amino acid replacements per site per year) ... in the last 55 million years (10)
." Contributing factors, such as changes in population size and others, can be excluded because the two genes are studied in precisely the same sets of species. He brings to bear an interesting possibility for the erratic behavior of the Sod, Gpdh, and other molecular clocks, "from the perspective of gene sharing ... [namely], changes in protein function during evolution (11)
."
The book is thoroughly documented with more than 1165 references. It is in the citation of these references where I find fault, minor as this criticism may be. The references are listed in the order in which they are cited rather than alphabetically, which I found a handicap when going back to the references seeking to review a particular point or trying to refresh my memory as to what was the contribution of a particular author. There is also the awkward situation created by references added during revision or proof correction. Thus, we see on p. 2, for example, a citation to references "5, 6, 1117," "7, 1118, 1119," and to "8–10, 1117." These bibliographic blemishes notwithstanding, Gene Sharing and Evolution is a remarkable book, which geneticists and evolutionists are likely to read with great interest and great profit.
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FOOTNOTES
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