Preface

The book Gene Duplication consists of 21 chapters divided in 3 parts: General Aspects, A Look at Some Gene Families and Examining Bundles of Genes.

The importance of the study of Gene Duplication stems from the realization that the dynamic process of duplication is the "sine qua non" underlying the evolution of all living matter. Genes may be altered before or after the duplication process thereby undergoing neofunctionalization, thus creating in time new organisms which populate the Earth.

Osaka (Chapter I) suggests that similarities in amino acid sequences exhibited by paralogous proteins prove that evolution proceeds via in toto gene duplication. If the ancestral and the newly created gene perform the same function, the new gene would be labeled a subfunctional gene. It should be added that such a duplicated gene encoding an identical product might also be engaged by different cellular regulatory signals (e.g. methylation of nucleotide sites) which in turn, could hamper the expression of such a duplicated gene. (See e.g. Woody et al. Chapter 3). If this duplicated gene subsequently undergoes mutations that allow a function for the new gene that is different from the parent gene (neofunctionalization) that would represent a far more positive evolutionary event. The first three chapters in this book focus on such in toto gene duplications whereby in evolutionary time neofunctionalization could have taken hold. There are also several specific cicumscribed examples given in this book. (See e.g. Majee&Kaur, Chapter 12). Undoubtedly, duplication contributes substantially to the formation of new genes. But there is a caveat: In time, the majority of duplicated genes mutates into oblivion.

In recent years, however, attention has been paid to another possible path for creating a new gene: The formation of the chimeric gene, a gene immediately ready for a new function. Such a gene might result from altering the position of spliced introns, or more likely from retropositioning of a new encoding domain into the gene: I.e. partial gene duplications and combination. It is obvious that such processes are particularly suited for the creation of genes encoding multi-domain proteins and that they may accelerate considerably the natural process of neofunctionalization. (See Hatje et al.Chapter 4; Friedberg, Chapter 5; Toll-Riera et al. Chapter 6 and Iwashita et al. Chapter 21). Retrotransposons are capable of promoting such segmental duplications.

### XIV Preface

"Retroduplication" contributes significantly to the formation of new genes. These genes, in turn may also be duplicated and eventually be erased into oblivion by mutations.

> **Prof. Felix Friedberg** Howard University Medical School, Washington DC, USA

**Part 1** 

**General Aspects** 

**1** 

Jinya Otsuka

*Japan*

**A Theoretical Scheme of the Large-Scale** 

In the famous book "The Origin of Species" by Darwin (1859), the gradual accumulation of selectively advantageous variants has been proposed qualitatively by obtaining a hint from the artificial selection of domestic animals and plants as well as from the observation of unique species in a geographically isolated region. The core of this proposal has become evident, after the re-discovery of Mendelian heredity, by the detection of hereditary variants, i. e., mutants, and extensive investigations have been carried out for the behavior of mutants especially in the *Drosophila* population (Dobzhansky, 1941; Mayer, 1942; Huxley, 1943; Simpson, 1944). In parallel, Darwinian evolution is mathematically formulated in population genetics to estimate the probability that a spontaneously generated mutant is fixed in, or eliminated from, the population according to the positive or negative value of a selective parameter (Fisher, 1930; Wright, 1949). Although the accumulation of such mutants as those found in the *Drosophila* was supposed to explain the whole process of evolution, the mutants detected at that time were mainly due to the point mutations in established genes, and most of them were defective. Thus, doubts remain about whether the gradual accumulation of such mutants gives rise to radically new organs such as wings and eyes. Another criticism against the survival of the fittest in Darwinian evolution is also raised by the ecological fact of diversity that different styles of organisms coexist in the same area

The gene and genome sequencing, which started in the latter half of the last century, has brought new information about the evolution of organisms. First, the amino acid sequence similarities of paralogous proteins strongly suggest that the repertoire of protein functions has been expanded by gene duplication, succeeding nucleotide base substitutions, partial insertion and deletion, and further by domain shuffling in some cases (Ingram, 1963; Gilbert, 1978; Ferris & White, 1979). Such examples are now increasing, proposing many protein families and superfamilies. Second, the clustering analysis of proteomes reveals a characteristic feature that the proteins functioning in the core part are essentially common to both prokaryotes and eukaryotes, and that the decisive difference in gene repertoire between the organisms is observed in the peripheral parts displaying different living styles (Kojima & Otsuka, 2000 a, b, c; Kojima & Otsuka, 2002). These sequence data are now

compiled into databases (e. g., Wheeler et al., 2004; Birney et al., 2006).

**1. Introduction**

(Nowak et al., 1994).

**Evolution by Generating New Genes** 

**from Gene Duplication**

*JO Institute of Biophysics, Tokyo,* 
