Mitochondrial DNA and two perspectives on evolutionary genetics

This essay reviews comparative studies of animal mitochondrial DNA (mtDNA), with emphasis on findings made and ideas developed at Berkeley. It argues that such studies are bringing together two previous paths of progress in evolutionary biology. One path is that of those who worked far above the species level and were concerned with genealogical trees, time scales and the accumulation of new mutations on surviving molecular lineages. The other path is that of those who worked at and below the species level and were concerned mainly with population structure, migration and the frequencies of alleles that existed in an ancestral population. This fusion of paths is made possible by the high rate at which mutations accumulate on mtDNA lineages and by this molecule's uniparental and apparently haploid mode of inheritance. These properties make mtDNA a superb tool for building trees and time scales relating molecular lineages at and below the species level. In addition, owing to its mode of inheritance, mtDNA is more sensitive to bottlenecks in population size and to population subdivision than are nuclear genes. Joint comparative studies of both mtDNA and nuclear DNA variability give us valuable insights into how effective population size has varied through time. Such studies also give insight into the conditions under which mtDNA from one species can colonize another species.     

Mitochondrial genetics and obesity: evolutionary adaptation and contemporary disease susceptibility

Obesity is a leading risk factor for a variety of metabolic diseases including cardiovascular disease, diabetes, and cancer. Although in its simplest terms, obesity may be thought of as a consequence of excessive caloric intake and sedentary lifestyle, it is also evident that individual propensity for weight gain can vary. The etiology of individual susceptibility to obesity seems to be complex—involving a combination of environmental–genetic interactions. Herein, we suggest that the mitochondrion plays a major role in influencing individual susceptibility to this disease via mitochondrial–nuclear interaction processes and that environmentally influenced selection events for mitochondrial function that conveyed increased reproductive and survival success during the global establishment of human populations during prehistoric times can influence individual susceptibility to weight gain and obesity.     

Mitochondrial DNA nucleoids determine mitochondrial genetics and dysfunction

Mitochondrial DNA plays a crucial role in cellular homeostasis; however, the molecular mechanisms underlying mitochondrial DNA inheritance and propagation are only beginning to be understood. To ensure the distribution and propagation of the mitochondrial genome, mitochondrial DNA is packaged into macromolecular assemblies called nucleoids, composed of one or more copies of mitochondrial DNA and associated proteins. We review current research on the mitochondrial nucleoid, including nucleoid-associated proteins, nucleoid dynamics within the cell, potential mechanisms to ensure proper distribution of nucleoids, and the impact of nucleoid organization on mitochondrial dysfunction. The nucleoid is the molecular organizing unit of mitochondrial genetics, and is the site of interactions that ultimately determine the bioenergetic state of the cell as a whole. Current and future research will provide essential insights into the molecular and cellular interactions that cause bioenergetic crisis, and yield clues for therapeutic rescue of mitochondrial dysfunction.     

Mitochondrial DNA variation and the evolutionary history of cryptic Gammarus fossarum types

The evolutionary history of the cryptic Gammarus fossarum species complex (Crustacea, Amphipoda) in Central Europe was approached by investigating the genetic variation in populations of a natural contact zone. Nucleotide sequence variation of a 395-bp segment of the mitochondrial 16S rRNA gene was compared to that of six nuclear allozyme loci. Three major mtDNA lineages were found, the eastern clade being consistent with the former allozyme type A. The two western clades (types B and C) were not distinguished previously. Strong sequence divergence and correlation with nuclear genetic isolation in syntopic populations, however, justifies the specific status of the three G. fossarum types. The common speciation event is believed to be very old (Miocene). The within-type mtDNA variation is probably molded by the ice ages, with type B populations being most affected. Moreover, the patch-like distribution of mtDNA type B lineages in an area near the contact zone corroborates the hypothesis of a recent colonization.     

鱼类线粒体DNA及其在分子群体遗传研究中的应用

鱼类是脊椎动物亚门中种属数量最多的类群,分布广泛,起源复杂,拥有丰富的遗传多样性.多种自然和人为因素对鱼类遗传资源存在不同程度的作用,对鱼类生存和进化有重要影响.采用分子手段探讨鱼类遗传资源现状,可为遗传育种、鱼类进化研究和遗传资源保护等提供一定科学依据.以鱼类线粒体DNA(mtDNA)为代表的分子标记技术已被用于研究鱼类群体遗传结构及其与影响因素间的关系.本文综述了鱼类mtDNA的结构特征及其在鱼类分子群体遗传研究中的应用,对了解和运用mtDNA等分子标记研究鱼类群体遗传具有一定参考价值.     

Molecular genetics of DNA repair in higher plants

Damage to DNA occurs in all living things, and the toxicity and/or mutagenicity of the damage products are reduced through the activities of one or more DNA repair pathways. The mechanisms of DNA repair are best understood in microorganisms and mammals, but the field has recently expanded to include both plants and lower animals. These recent advances in our understanding of the molecular and classical genetics of DNA repair in higher plants include such aspects as the repair of UV-induced pyrimidine dimers, the correction of mismatched bases, and the rejoining of double strand breaks.     

Mitochondrial genetics

Summary Cytoplasmic petite mutants of Saccharomyces cerevisiae carrying the gene conferring the resistance to chloramphenicol on one hand and the gene conferring the resistance to erythromycin on the other, have been crossed with each other. The two types of petites differed in the buoyant densities of their mitochondrial DNA. A novel type of evidence has been adduced, that the two genes are indeed located on mitochondrial DNA. Diploid petite recombinants were found, carrying both genes and containing not a mixture of the two parental DNAs but a new species of mitochondrial DNA of intermediate buoyant density. Recombination of mitochondrial genes involves therefore breakage and reunion of DNA molecules. New suppressiveness, different from the two parental ones, can result from the recombination of mitochondrial DNA. Recombination between petite mutants implies that the mitochondrial recombination enzymes have to be synthesized on cytosol ribosomes.     

Neandertal evolutionary genetics: mitochondrial DNA data from the iberian peninsula

Mitochondrial DNA (mtDNA) was retrieved for the first time from a Neandertal from the Iberian Peninsula, excavated from the El Sidrón Cave (Asturias, North of Spain), and dated to ca. 43,000 years ago. The sequence suggests that Iberian Neandertals were not genetically distinct from those of other regions. An estimate of effective population size indicates that the genetic history of the Neandertals was not shaped by an extreme population bottleneck associated with the glacial maximum of 130,000 years ago. A high level of polymorphism at sequence position 16258 reflects deeply rooted mtDNA lineages, with the time to the most recent common ancestor at ca. 250,000 years ago. This coincides with the full emergence of the "classical" Neandertal morphology and fits chronologically with a proposed speciation event of Homo neanderthalensis.     

Mitochondrial genetics and disease

Mitochondrial respiratory chain diseases are a highly diverse group of disorders whose main unifying characteristic is the impairment of mitochondrial function. As befits an organelle containing gene products encoded by both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA), these diseases can be caused by inherited errors in either genome, but a surprising number are sporadic, and a few are even caused by environmental factors.     

Mitochondrial DNA: a tool for populational genetics studies.

Mitochondria are cellular organelles that have the function of the oxidative phosphorilation and the formation of ATP. In humans, the mtDNA is a double-stranded, circular, covalent closed molecule of 16.5 kb. The mtDNA is inherited as a haploid from the mother and heteroplasmy has been found rarely. From a populational perspective, it could be considered as a system of small, sexually isolated demes, or clonal lineages, with an evolutionary rate 5 to 10 times faster than the nuclear genome. All these characteristics make this molecule ideal for evolutionary studies. We present two applications of this molecule in genetical studies. One of these is referred to the Balearic Islands populations, Majorca, Minorca, Ibiza, and Chuetas. The other example is the populational dynamics of the different mitochondrial haplotypes in Drosophila subobscura. We also discuss the importance of nuclear markers to complete these studies as well as the study of the Y chromosome to compensate the bias produced by the study of only the mtDNA.     

Mitochondrial genetics and human disease

Mitochondria contain a molecular genetic system to express the 13 protein components of the electron transport system encoded in the mitochondrial genome (mtDNA). Defects in the function of this system result in some diaseases, many of which are multisystem disorders, prominently involving highly aerobic, postmitotic tissues. These defects can be caused by large-scale rearrangements of mtDNA, by point mutations, or by nuclear gene mutations resulting in abnormalities in mtDNA. Although any of these mutations would be expected to produce a similar clinical phenotype by compromising oxidative phosphorylation, the surprising and puzzling result is that different clinical phenotypes are generally associated with specific mtDNA mutations. Moreover, the same mutation can produce a distinct clinical phenotype in different individuals or pedigrees. MtDNA rearrangements are also found in aged individuals, but at a subclinical level, suggesting that normal and pathological processes can differ by the effect of genetic or environmental factors on the error rate of mtDNA replication.     

微卫星分子标记在濒危动物保护遗传学研究中的应用

微卫星DNA广泛分布于真核生物基因组中,具有多态性高、共显性遗传、选择中性、易于操作等特点,是一种极具应用价值的分子遗传标记,近年来在濒危动物保护遗传学研究中得到越来越多的应用。微卫星DNA高度多态性提供的高分辨率遗传信启,使其不仅适合个体水平的亲子鉴定与交配系统研究,而且也已成为种群遗传结构与多样性分析的有效分子标记。微卫星分析所需的DNA量极少,用非损伤性方法获取的极少量样品或陈旧样品就能用于有效分析,方便了濒危动物野外调查工作的开展,并且可以利用年代久远的馆藏历史标本揭示种群的重要历史进程。另外,某些微卫星DNA大小在近缘物种间可相互区分,这使得部分物种的DNA分子鉴别将更为简便。但微卫星分子标记的座位筛选和特异引物开发耗时费力,一定程度上限制了其广泛应用。针对不同的研究目的选择合适的分子标记方法将有助于更好的揭示问题本质。     

The genetics of evolutionary radiations

With the realization that much of the biological diversity on Earth has been generated by discrete evolutionary radiations, there has been a rapid increase in research into the biotic (key innovations) and abiotic (key environments) circumstances in which such radiations took place. Here we focus on the potential importance of population genetic structure and trait genetic architecture in explaining radiations. We propose a verbal model describing the stages of an evolutionary radiation: first invading a suitable adaptive zone and expanding both spatially and ecologically through this zone; secondly, diverging genetically into numerous distinct populations; and, finally, speciating. There are numerous examples of the first stage; the difficulty, however, is explaining how genetic diversification can take place from the establishment of a, presumably, genetically depauperate population in a new adaptive zone. We explore the potential roles of epigenetics and transposable elements (TEs), of neutral process such as genetic drift in combination with trait genetic architecture, of gene flow limitation through isolation by distance (IBD), isolation by ecology and isolation by colonization, the possible role of intra‐specific competition, and that of admixture and hybridization in increasing the genetic diversity of the founding populations. We show that many of the predictions of this model are corroborated. Most radiations occur in complex adaptive zones, which facilitate the establishment of many small populations exposed to genetic drift and divergent selection. We also show that many radiations (especially those resulting from long‐distance dispersal) were established by polyploid lineages, and that many radiating lineages have small genome sizes. However, there are several other predictions which are not (yet) possible to test: that epigenetics has played a role in radiations, that radiations occur more frequently in clades with small gene flow distances, or that the ancestors of radiations had large fundamental niches. At least some of these may be testable in the future as more genome and epigenome data become available. The implication of this model is that many radiations may be hard polytomies because the genetic divergence leading to speciation happens within a very short time, and that the divergence history may be further obscured by hybridization. Furthermore, it suggests that only lineages with the appropriate genetic architecture will be able to radiate, and that such a radiation will happen in a meta‐population environment. Understanding the genetic architecture of a lineage may be an essential part of accounting for why some lineages radiate, and some do not.     

The evolutionary genetics of canalization

Evolutionary genetics has recently made enormous progress in understanding how genetic variation maps into phenotypic variation. However why some traits are phenotypically invariant despite apparent genetic and environmental changes has remained a major puzzle. In the 1940s, Conrad Hal Waddington coined the concept and term "canalization" to describe the robustness of phenotypes to perturbation; a similar concept was proposed by Waddington's contemporary Ivan Ivanovich Schmalhausen. This paper reviews what has been learned about canalization since Waddington. Canalization implies that a genotype's phenotype remains relatively invariant when individuals of a particular genotype are exposed to different environments (environmental canalization) or when individuals of the same single- or multilocus genotype differ in their genetic background (genetic canalization). Consequently, genetic canalization can be viewed as a particular kind of epistasis, and environmental canalization and phenotypic plasticity are two aspects of the same phenomenon. Canalization results in the accumulation of phenotypically cryptic genetic variation, which can be released after a "decanalizing" event. Thus, canalized genotypes maintain a cryptic potential for expressing particular phenotypes, which are only uncovered under particular decanalizing environmental or genetic conditions. Selection may then act on this newly released genetic variation. The accumulation of cryptic genetic variation by canalization may therefore increase evolvability at the population level by leading to phenotypic diversification under decanalizing conditions. On the other hand, under canalizing conditions, a major part of the segregating genetic variation may remain phenotypically cryptic; canalization may therefore, at least temporarily, constrain phenotypic evolution. Mechanistically, canalization can be understood in terms of transmission patterns, such as epistasis, pleiotropy, and genotype by environment interactions, and in terms of genetic redundancy, modularity, and emergent properties of gene networks and biochemical pathways. While different forms of selection can favor canalization, the requirements for its evolution are typically rather restrictive. Although there are several methods to detect canalization, there are still serious problems with unambiguously demonstrating canalization, particularly its adaptive value.