Elsevier

Gene

Volume 238, Issue 1, 30 September 1999, Pages 195-209
Gene

Evolutionary genomics in Metazoa: the mitochondrial DNA as a model system

https://doi.org/10.1016/S0378-1119(99)00270-XGet rights and content

Abstract

One of the most important aspects of mitochondrial (mt) genome evolution in Metazoa is constancy of size and gene content of mtDNA, whose plasticity is maintained through a great variety of gene rearrangements probably mediated by tRNA genes. The trend of mtDNA to maintain the same genetic structure within a phylum (e.g., Chordata) is generally accepted, although more recent reports show that a considerable number of transpositions are observed also between closely related organisms. Base composition of mtDNA is extremely variable. Genome GC content is often low and, when it increases, the two complementary bases distribute asymmetrically, creating, particularly in vertebrates, a negative GC-skew. In mammals, we have found coding strand base composition and average degree of gene conservation to be related to the asymmetric replication mechanism of mtDNA. A quantitative measurement of mtDNA evolutionary rate has revealed that each of the various components has a different evolutionary rate. Non-synonymous rates are gene specific and fall in a range comparable to that of nuclear genes, whereas synonymous rates are about 22-fold higher in mt than in nuclear genes. tRNA genes are among the most conserved but, when compared to their nuclear counterparts, they evolve 100 times faster. Finally, we describe some molecular phylogenetic reconstructions which have produced unexpected outcomes, and might change our vision of the classification of living organisms.

Introduction

There are several good reasons for using the mitochondrial (mt) genome as a model system in studies on evolutionary genomics.

The mtDNA is an organellar genome and an indispensable component of all eukaryotic cells able to respire which, thus, possess mitochondria. Since the substantial increase in oxygen in the atmosphere in the Proterozoic (Morris, 1998), mtDNA has evolved together with the main cellular genome, the nuclear genome (nDNA), and when present with the other organellar genome, i.e., chloroplast DNA. Therefore, it contains important elements which might tell us the evolutionary history of the organism to which it belongs and the functional constraints under which it has evolved.

Because of its reduced size, it was the first eukaryotic genome to be completely sequenced in human (Anderson et al., 1981). We now have a large number of mitochondrial genomes completely or almost completely sequenced from a great variety of organisms: from protists to plants and mammals. The accumulated data are stored in a structured form in a specialized database, MitBASE (http://www.ebi.ac.uk/htbin/Mitbase/mitbase.pl), which is organized as a network of nodes, one for each group of organisms — protists, fungi, plants, invertebrates, vertebrates, humans — under the responsibility of distinguished scientists. MitBASE allows the end user to navigate from one organism to another, performing sophisticated comparative studies.

In contrast with the few completely sequenced prokaryotic or nuclear genomes now available on which only comparative studies can be performed, mtDNA allows us to carry out real evolutionary analyses thanks to the opportunity it offers to introduce a time dimension. The difference between comparative and evolutionary genomics can be regarded as the difference between kinematics and dynamics in physical systems. Kinematics is the mere description of a given process which, once introduced into the proper temporal framework describing forces and constraints operating on the system, becomes dynamic, i.e., modality of evolution.

Indeed, for the mt genome, particularly in animal cells, we now have sufficient information to start evolutionary studies.

We are aware that the mitochondrial genome as a model system may suffer from severe limitations, as it represents only a very limited fraction of the information content of eukaryotic cells. Hence the conclusions drawn are not always valid also for the much more complex nuclear genomes. Anyway, we can build a model system, devising appropriate algorithms and software for analyses with the hope of throwing light on the dynamics of the evolutionary process.

The mt genome shows a great variability in structure, gene content, organization and mode of expression in the different organisms. This extraordinary diversity probably reflects the different evolutionary pathways that gave rise in the eukaryotic cell to segregation of genetic information into different cellular compartments. For the endosymbiotic theory, postulating mitochondria derive from prokaryotes which established a symbiotic relationship with the primitive eukaryotic cell, it can also mean that different microorganisms were responsible for the endosymbiotic event in different lineages.

Recently, unexpected findings have enlarged the scenario of gene organization in eukaryotes. It has been shown recently that hydrogenosomes — membrane-bound organelles present in some anaerobic protozoa and chytridiomycete fungi able to produce molecular hydrogen — also possess a genome of mitochondrial descent (Akhmanova et al., 1998). Furthermore, the recent discovery of genes of mitochondrial origin in amitochondriate protozoa questions the commonly accepted hypothesis that they branched off early from other eukaryotes, before the endosymbiotic event from which mitochondria originated (Embley and Hirt, 1998). A later loss of mitochondria in these organisms, probably occurring independently in different lineages, would thus be a most likely event. These novel data could open for us a new concept of cell organization and evolutionary avenues.

In this report, restricted to the mt genome of Metazoa, we summarize the work carried out in our laboratory, devoted to the study of mtDNA since its discovery, and emphasize the most peculiar evolutionary aspects of mammalian mt genomes regarding the coding region. After a brief review of genomic organization in Metazoa, we shall focus our attention on the compositional constraints of mtDNA which significantly bias its evolutionary process. Finally, some issues related to the nucleotide substitution rate and to the molecular phylogeny of mammals will be discussed.

Section snippets

Sequence dataset

Table 1 reports the list of metazoan mt genomes completely sequenced so far. An equal number is present in researchers' drawers and thus, unfortunately, is not yet available. Analysis of these genomes might shed light on metazoan evolution, which has occurred in a time span much before the Cambrian, thus dating as far back as one billion years ago in accordance with recent molecular and paleontological estimates (Seilacher et al., 1998, Wray et al., 1996).

Gene organization

In contrast with the high variability displayed by the mt genomes of lower eukaryotes and plants, evolutionary forces moulded metazoan mtDNA into a molecule characterized by compact arrangement, constancy of gene content, and presence of a main non-coding region. However, the progressive acquisition of new sequences into mtDNA databases has shown an increasing number of mt genomes whose structure deviates from the previous congruent picture of this molecule.

In general, mtDNA is described as a

Asymmetry in base composition

The base composition of the mt genome in Metazoa displays peculiar features. The GC content calculated for the mt genomes of several metazoan taxa (Table 2) and for various mammalian orders (Table 3) is highly variable. It is extremely low in the genomes of insects and nematodes, and increases in vertebrates, reaching the highest value in birds, mammals (particularly primates) and teleostei.

Based on the first available mitochondrial sequences, we observed an asymmetric distribution of the

Evolutionary rate

The peculiar features of the mt genome, such as maternal inheritance, lack of recombination and presence of orthologous genes, together with the simplicity of its extraction and sequencing, have made this molecule the best tool for studying molecular evolution under both qualitative and quantitative aspects.

It has been widely reported that the mt genome generally evolves much faster than the nuclear genome (Brown et al., 1979, Brown et al., 1982, Wilson et al., 1985). This statement, based on

Phylogenetic reconstruction

The mitochondrial genome has revealed a powerful tool to face the complex problem of higher-level classification in Mammalia. In particular, two issues can be addressed: (i) the reconstruction of the phylogenetic interordinal relationships; and (ii) the testing of monophyly or polyphyly of each order.

The analysis of complete mammalian mt genomes has generated many unexpected and surprising results, mainly concerning the polyphyly of Rodentia and Artiodactyla, the unreliability of the cohort

Conclusions

The studies reported here reveal a number of important features and mechanisms which have moulded the evolution of the mt genome of Metazoa.

The dimension and gene content of mtDNA, kept frozen in more than 800 My, clearly indicate that these features represent a selective evolutionary advantage. The metazoan mt genome, however, expresses its plasticity in the continuous and wide rearrangement of genes, observed in the various lineages, and in the modalities of interaction with the co-evolving

Note added in proof

A comprehensive review concerning gene organization and evolution of gene order in animal mitochondrial genomes has recently been published (Boore et al., 1999) where some new complete genomes [e.g. Aythya americana (redhead duck, AF090337); Vidua chalybeata (village indigobird, AF090341); Falco peregrinus (peregrine falcon, AF090338); Smithornis sharpei (broadbill, AF090340)], are described even if they are still not available in the public databases. Furthermore, five complete mtDNA sequences

Acknowledgements

This work has been supported by Training and Mobility Research European Project ERBFMRX-CT98-0221 and by MURST, Italy. We would like to thank Joerg Hauf for providing unpublished sequence data and M. Lonigro for the revision of the manuscript.

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