抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

http://ggdpathway.wustl.edu/files/2014/08/ACMG-Guidelines-2015_Richards-et-al.pdf

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

We present here a framework for the study of molecular variation within a single species. Information on DNA haplotype divergence is incorporated into an analysis of variance format, derived from a matrix of squared-distances among all pairs of haplotypes. This analysis of molecular variance (AMOVA) produces estimates of variance components and F-statistic analogs, designated here as phi-statistics, reflecting the correlation of haplotypic diversity at different levels of hierarchical subdivision. The method is flexible enough to accommodate several alternative input matrices, corresponding to different types of molecular data, as well as different types of evolutionary assumptions, without modifying the basic structure of the analysis. The significance of the variance components and phi-statistics is tested using a permutational approach, eliminating the normality assumption that is conventional for analysis of variance but inappropriate for molecular data. Application of AMOVA to human mitochondrial DNA haplotype data shows that population subdivisions are better resolved when some measure of molecular differences among haplotypes is introduced into the analysis. At the intraspecific level, however, the additional information provided by knowing the exact phylogenetic relations among haplotypes or by a nonlinear translation of restriction-site change into nucleotide diversity does not significantly modify the inferred population genetic structure. Monte Carlo studies show that site sampling does not fundamentally affect the significance of the molecular variance components. The AMOVA treatment is easily extended in several different directions and it constitutes a coherent and flexible framework for the statistical analysis of molecular data.

/pdf/analysis-of-molecular-variance-inferred-from-metric-89hl32sg7j.pdf

Analysis of molecular variance inferred from metric distances among DNA haplotypes: application to human mitochondrial DNA restriction data.

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria (MCAT). Median and maximum life spans were maximally increased (averages of 5 months and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.

/pdf/extension-of-murine-life-span-by-overexpression-of-catalase-26vg2nbr62.pdf

Extension of murine life span by overexpression of catalase targeted to mitochondria.

https://www.cell.com/cell/pdf/0092-8674(90)90059-N.pdf

Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation

Human mitochondrial DNA was obtained from peripheral blood platelets donated by the members of several independent families. The samples were screened for nucleotide sequence polymorphisms between individuals within these families. In each family in which we were able to detect a distinctly different restriction endonuclease cleavage pattern between the parents, the progeny exhibited the maternal cleavage pattern. Informative polymorphisms were detected for Hae II (PuGCGCPy) in a three-generation family composed of 33 members, for HincII (GTPyPuAC) in a two-generation family composed of four members, and for Hae III(GGCC) in a two-generation family composed of four members. The Hae II polymorphism was analyzed through all three generations in both the maternal and paternal lines. The results of this study demonstrate that human mitochondrial DNA is maternally inherited. The techniques described for using peripheral blood platelets as a source of human mitochondrial DNA represent a convenient way to obtain data on mitochondrial DNA variation in both individuals and populations.

https://www.pnas.org/content/pnas/77/11/6715.full.pdf

Maternal inheritance of human mitochondrial DNA

Studies of diseases caused by mitochondrial DNA mutations suggest that a variety of degenerative processes may be associated with defects in oxidative phosphorylation (OXPHOS). Application of this hypothesis has provided new insights into such diverse clinical problems as ischemic heart disease, late-onset diabetes, Parkinson's disease, Alzheimer's disease, and aging.

https://science.sciencemag.org/content/sci/256/5057/628.full.pdf

Mitochondrial genetics: a paradigm for aging and degenerative diseases?

INTRODUCTION . . _ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 175 THE HUMAN MITOCHONDRIAL DNA AND OXIDATIVE PHOSPHORYLATION 1176 Mitochondrial Biogenesis ... 1 176 Mitochondrial OXPHOS Complexes and their Synthesis 1 178 Developmental Regulation of Nuclear OXPHOS Genes 1179 Mitochondrial DNA Genetics 1 1 8 1 MITOCHONDRIAL DNA MUTATIONS AND DISEASE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 183 Missense Mutations 1184 Biogenesis Mutations 1 1 88 Insertion-Deletion Mutations . 1 192 Copy Number Mutations 1 195 DEFECTS IN NUCLEAR-CYTOPLASMIC INTERACTIONS . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . 1 195 THE PROGRESSION OF OXPHOS DISEASES AND AGING 1 196 EVIDENCE FOR OXPHOS DEFECTS IN COMMON DEGENERATIVE DISEASES . . ... . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . 1201 METABOLIC AND GENETIC THERAPY OF OXPHOS DEFECTS 1206

Douglas C. Wallace

Papers

Extension of murine life span by overexpression of catalase targeted to mitochondria.

Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation

Maternal inheritance of human mitochondrial DNA

Mitochondrial genetics: a paradigm for aging and degenerative diseases?

Diseases of the mitochondrial DNA.