遗传多样性上限假说所揭示的进化历程

作为生物进化的两个主流理论, 中性学说和现代达尔文进化理论相对系统地揭示了进化机理和历程, 但也都有缺陷, 比如对某些重大进化现象如遗传等距离和重叠位点(Overlap sites)的忽视, 对复杂性的视而不见, 对遗传多样性的片面解读, 以及与化石证据相悖等。遗传多样性上限假说(Maximum genetic diversity hypothesis, MGD)通过对遗传等距离现象的重新解读, 给出了复杂性的量化定义和可操作研究手段, 提出了重叠特征和遗传多样性具有上限等结论。它对人猿分类关系和现代人多地区起源的分子解读结论, 与独立的化石证据契合度较高, 重新肯定了中国在人类发展中的关键作用, 点出了流行分子结论的荒谬在于误用了极限距离。该理论同时对复杂性状和复杂疾病的遗传机制研究具有指导意义。文章对多种酵母、鱼类、灵长类的细胞色素c进行序列比对, 独立验证了MGD假说的部分论断, 并解释了重叠位点在遗传距离计算上的重要意义。MGD假说中的上限或最佳平衡概念, 与传统国学和中医阴阳中庸思想对宇宙基本规律的描述是一脉相承的。     

Application of network methods for understanding evolutionary dynamics in discrete habitats

In populations occupying discrete habitat patches, gene flow between habitat patches may form an intricate population structure. In such structures, the evolutionary dynamics resulting from interaction of gene‐flow patterns with other evolutionary forces may be exceedingly complex. Several models describing gene flow between discrete habitat patches have been presented in the population‐genetics literature; however, these models have usually addressed relatively simple settings of habitable patches and have stopped short of providing general methodologies for addressing nontrivial gene‐flow patterns. In the last decades, network theory – a branch of discrete mathematics concerned with complex interactions between discrete elements – has been applied to address several problems in population genetics by modelling gene flow between habitat patches using networks. Here, we present the idea and concepts of modelling complex gene flows in discrete habitats using networks. Our goal is to raise awareness to existing network theory applications in molecular ecology studies, as well as to outline the current and potential contribution of network methods to the understanding of evolutionary dynamics in discrete habitats. We review the main branches of network theory that have been, or that we believe potentially could be, applied to population genetics and molecular ecology research. We address applications to theoretical modelling and to empirical population‐genetic studies, and we highlight future directions for extending the integration of network science with molecular ecology.     

The Molecular Clock of Neutral Evolution Can Be Accelerated or Slowed by Asymmetric Spatial Structure

Over time, a population acquires neutral genetic substitutions as a consequence of random drift. A famous result in population genetics asserts that the rate, K, at which these substitutions accumulate in the population coincides with the mutation rate, u, at which they arise in individuals: K = u. This identity enables genetic sequence data to be used as a “molecular clock” to estimate the timing of evolutionary events. While the molecular clock is known to be perturbed by selection, it is thought that K = u holds very generally for neutral evolution. Here we show that asymmetric spatial population structure can alter the molecular clock rate for neutral mutations, leading to either K<u or K>u. Our results apply to a general class of haploid, asexually reproducing, spatially structured populations. Deviations from K = u occur because mutations arise unequally at different sites and have different probabilities of fixation depending on where they arise. If birth rates are uniform across sites, then K ≤ u. In general, K can take any value between 0 and Nu. Our model can be applied to a variety of population structures. In one example, we investigate the accumulation of genetic mutations in the small intestine. In another application, we analyze over 900 Twitter networks to study the effect of network topology on the fixation of neutral innovations in social evolution.     

Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers

Unbiased readings of fossils are well known to contradict some of the popular molecular groupings among primates,particularly with regard to great apes and tarsiers.The molecular methodologies today are however flawed as they are based on a mistaken theoretical interpretation of the genetic equidistance phenomenon that originally started the field.An improved molecular method the ’slow clock’ was here developed based on the Maximum Genetic Diversity hypothesis,a more complete account of the unified changes in genotypes and phenotypes.The method makes use of only slow evolving sequences and requires no uncertain assumptions or mathematical corrections and hence is able to give definitive results.The findings indicate that humans are genetically more distant to orangutans than African apes are and separated from the pongid clade ～17.6 million years ago.Also,tarsiers are genetically closer to lorises than simian primates are.Finally,the fossil times for the radiation of mammals at the K/T boundary and for the Eutheria-Metatheria split in the Early Cretaceous were independently confirmed from molecular dating calibrated using the fossil split times of gorilla-orangutan,mouse-rat,and opossum-kangaroo.Therefore,the re-established primate phylogeny indicates a remarkable unity between molecules and fossils.     

“Everything You Always Wanted to Know about Sex (but Were Afraid to Ask)” in Leishmania after Two Decades of Laboratory and Field Analyses

Leishmaniases remain a major public health problem today (350 million people at risk, 12 million infected, and 2 million new infections per year). Despite the considerable progress in cellular and molecular biology and in evolutionary genetics since 1990, the debate on the population structure and reproductive mode of Leishmania is far from being settled and therefore deserves further investigation. Two major hypotheses coexist: clonality versus sexuality. However, because of the lack of clear evidence (experimental or biological confirmation) of sexuality in Leishmania parasites, until today it has been suggested and even accepted that Leishmania species were mainly clonal with infrequent genetic recombination (see [1] for review). Two recent publications, one on Leishmania major (an in vitro experimental study) and one on Leishmania braziliensis (a population genetics analysis), once again have challenged the hypothesis of clonal reproduction. Indeed, the first study experimentally evidenced genetic recombination and proposed that Leishmania parasites are capable of having a sexual cycle consistent with meiotic processes inside the insect vector. The second investigation, based on population genetics studies, showed strong homozygosities, an observation that is incompatible with a predominantly clonal mode of reproduction at an ecological time scale (∼20–500 generations). These studies highlight the need to advance the knowledge of Leishmania biology. In this paper, we first review the reasons stimulating the continued debate and then detail the next essential steps to be taken to clarify the Leishmania reproduction model. Finally, we widen the discussion to other Trypanosomatidae and show that the progress in Leishmania biology can improve our knowledge of the evolutionary genetics of American and African trypanosomes.     

Characterizing the evolution of genetic variance using genetic covariance tensors

Determining how genetic variance changes under selection in natural populations has proved to be a very resilient problem in evolutionary genetics. In the same way that understanding the availability of genetic variance within populations requires the simultaneous consideration of genetic variance in sets of functionally related traits, determining how genetic variance changes under selection in natural populations will require ascertaining how genetic variance–covariance (G) matrices evolve. Here, we develop a geometric framework using higher-order tensors, which enables the empirical characterization of how G matrices have diverged among populations. We then show how divergence among populations in genetic covariance structure can then be associated with divergence in selection acting on those traits using key equations from evolutionary theory. Using estimates of G matrices of eight male sexually selected traits from nine geographical populations of Drosophila serrata, we show that much of the divergence in genetic variance occurred in a single trait combination, a conclusion that could not have been reached by examining variation among the individual elements of the nine G matrices. Divergence in G was primarily in the direction of the major axes of genetic variance within populations, suggesting that genetic drift may be a major cause of divergence in genetic variance among these populations.     

Finding new clock components: past and future

The molecular mechanism of circadian clocks has been unraveled primarily by the use of phenotype-driven (forward) genetic analysis in a number of model systems. We are now in a position to consider what constitutes a clock component, whether we can establish criteria for clock components, and whether we have found most of the primary clock components. This perspective discusses clock genes and how genetics, molecular biology, and biochemistry have been used to find clock genes in the past and how they will be used in the future.     

Presidential address: rediscovering parasites using molecular tools--towards revising the taxonomy of Echinococcus, Giardia and Cryptosporidium

Molecular biology has provided parasitologists with a fantastic variety of techniques that have had a major impact on research into parasites and parasitism. Molecular tools have revealed the extent and nature of genetic diversity in parasites and this information has made a significant contribution to studies on the population genetics and evolutionary biology of parasites. Similarly, epidemiology has benefited enormously from the application of molecular tools in terms of studying parasite life cycles and transmission, and in the development of specific and sensitive methods for diagnosis and surveillance. However, the theme I wish to develop in this paper is concerned with the contribution molecular tools have made to parasite taxonomy and systematics, and in particular, the fact that in many cases molecular tools are validating the proposals made many years ago by taxonomists and biologists which were discounted or not fully accepted at the time. To do this I have chosen four examples (Echinococcus, Entamoeba, Giardia, Cryptosporidium) where recent research involving molecular characterisation has confirmed observations made many years ago and has resulted in a need to revise the taxonomy of different groups of parasites.     

Adaptive Protein Evolution in Animals and the Effective Population Size Hypothesis

The rate at which genomes adapt to environmental changes and the prevalence of adaptive processes in molecular evolution are two controversial issues in current evolutionary genetics. Previous attempts to quantify the genome-wide rate of adaptation through amino-acid substitution have revealed a surprising diversity of patterns, with some species (e.g. Drosophila) experiencing a very high adaptive rate, while other (e.g. humans) are dominated by nearly-neutral processes. It has been suggested that this discrepancy reflects between-species differences in effective population size. Published studies, however, were mainly focused on model organisms, and relied on disparate data sets and methodologies, so that an overview of the prevalence of adaptive protein evolution in nature is currently lacking. Here we extend existing estimators of the amino-acid adaptive rate by explicitly modelling the effect of favourable mutations on non-synonymous polymorphism patterns, and we apply these methods to a newly-built, homogeneous data set of 44 non-model animal species pairs. Data analysis uncovers a major contribution of adaptive evolution to the amino-acid substitution process across all major metazoan phyla—with the notable exception of humans and primates. The proportion of adaptive amino-acid substitution is found to be positively correlated to species effective population size. This relationship, however, appears to be primarily driven by a decreased rate of nearly-neutral amino-acid substitution because of more efficient purifying selection in large populations. Our results reveal that adaptive processes dominate the evolution of proteins in most animal species, but do not corroborate the hypothesis that adaptive substitutions accumulate at a faster rate in large populations. Implications regarding the factors influencing the rate of adaptive evolution and positive selection detection in humans vs. other organisms are discussed.     

Bayesian models of episodic evolution support a late precambrian explosive diversification of the Metazoa

Multicellular animals, or Metazoa, appear in the fossil records between 575 and 509 million years ago (MYA). At odds with paleontological evidence, molecular estimates of basal metazoan divergences have been consistently older than 700 MYA. However, those date estimates were based on the molecular clock hypothesis, which is almost always violated. To relax this hypothesis, we have implemented a Bayesian approach to describe the change of evolutionary rate over time. Analysis of 22 genes from the nuclear and the mitochondrial genomes under the molecular clock assumption produced old date estimates, similar to those from previous studies. However, by allowing rates to vary in time and by taking small species-sampling fractions into account, we obtained much younger estimates, broadly consistent with the fossil records. In particular, the date of protostome-deuterostome divergence was on average 582 +/- 112 MYA. These results were found to be robust to specification of the model of rate change. The clock assumption thus had a dramatic effect on date estimation. However, our results appeared sensitive to the prior model of cladogenesis, although the oldest estimates (791 +/- 246 MYA) were obtained under a suboptimal model. Bayes posterior estimates of evolutionary rates indicated at least one major burst of molecular evolution at the end of the Precambrian when protostomes and deuterostomes diverged. We stress the importance of assumptions about rates on date estimation and suggest that the large discrepancies between the molecular and fossil dates of metazoan divergences might partly be due to biases in molecular date estimation.     

Understanding Neutral Genomic Molecular Clocks

The molecular clock hypothesis is a central concept in molecular evolution and has inspired much research into why evolutionary rates vary between and within genomes. In the age of modern comparative genomics, understanding the neutral genomic molecular clock occupies a critical place. It has been demonstrated that molecular clocks run differently between closely related species, and generation time is an important determinant of lineage specific molecular clocks. Moreover, it has been repeatedly shown that regional molecular clocks vary even within a genome, which should be taken into account when measuring evolutionary constraint of specific genomic regions. With the availability of a large amount of genomic sequence data, new insights into the patterns and causes of variation in molecular clocks are emerging. In particular, factors such as nucleotide composition, molecular origins of mutations, weak selection and recombination rates are important determinants of neutral genomic molecular clocks.     

On the virtues and pitfalls of the molecular evolutionary clock

"Informational" macromolecules--i.e., proteins and nucleic acids--have in their sequences a register of evolutionary history. Zuckerkandl and Pauling suggested in 1965 that these molecules might provide a "molecular clock" of evolution. The molecular clock would time evolutionary events and make it possible to reconstruct phylogenetic history--the branching relationships among lineages leading to modern species. Kimura's neutrality theory postulates that rates of molecular evolution are stochastically constant and, hence, that there is a molecular clock. A variety of tests have shown that molecular evolution does not behave like a stochastic clock. The variance in evolutionary rates is much too large and thus inconsistent with the neutrality theory. This, however, does not invalidate the clock, but rather leaves it without a theoretical foundation to anticipate its properties. Sequence comparisons show that molecular evolution is sufficiently regular to serve in many situations as a clock, but uncertainty concerning the properties of the clock (for example, about the circumstances that may yield large oscillations in substitution rates from time to time or from lineage to lineage) demands that it be used with caution. Few DNA or protein sequences are known from organisms that range from closely related, e.g., different mammals, to very remote, e.g., mammals and fungi. One example is cytochrome c, which has an acceptable clockwise behavior over the whole span, in spite of some irregularities. Another example is the copper-zinc superoxide dismutase (SOD), which behaves like a very erratic clock. The SOD average rate of amino acid substitution per 100 residues per 100 million years (MY) is 5.5 when fungi and animals are compared, 9.1 when comparisons are made between insects and mammals, and 27.8 when mammals are compared with each other. The question is which mode is more common over broad evolutionary spans: the regularity of cytochrome c or the capriciousness of SOD? Additional data sets will be required in order to obtain the answer and to develop expectations about the accuracy of the clock in particular instances. Until such data exist, conclusions solely based on the molecular clock are potentially fraught with error.     

Nikolaĭ Vladimirovich Timofeev-Resovskiĭ (1900-1981). (Essay on his life and works)

The article contains a brief review of the basic works (1925-1981) written by Nikolay V. Timofeeff-Ressovsky--one of the famous geneticist of the elapsing century, the founder of radiobiology and radiation genetics, biocenology and radioecology, a prominent evolutionary biologist. In genetics, his name is associated with the development of fundamental problems of population genetics, phenogenetics, gene interaction and investigations of the role of environmental and genetic factors in expression of different characters. Timofeeff-Ressovsky classical works on mutagenesis process and especially, radiation mutagenesis, promoted penetration of methods and approaches applied in molecular physics and chemistry, into genetic analysis, and accelerated forming of the modern molecular genetics. A special place in the development of population genetics is occupied by the hypothesis of microevolutionary process developed by Nikolay V. Timofeeff-Ressovsky along with other famous biologists in the end of the 30-ies. This hypothesis connected Darwin's evolutionary theory with rapidly developing concepts of genetics. In the last years of his life, Timofeeff-Ressovsky was especially interested in a global problem which was called by him "The Biosphere and Humanity". Here was especially strikingly shown the broadness of his approach to the analysis of the biosphere phenomena in the best traditions of the Russian natural science. In the course of time, the wealth of Nikolay V. Timofeeff-Ressovsky's scientific heritage not only remains valuable, but also takes on more profundity and value.     

Plant self-incompatibility in natural populations: a critical assessment of recent theoretical and empirical advances

Self-incompatibility systems in plants are genetic systems that prevent self-fertilization in hermaphrodites through recognition and rejection of pollen expressing the same allelic specificity as that expressed in the pistils. The evolutionary properties of these self-recognition systems have been revealed through a fascinating interplay between empirical advances and theoretical developments. In 1939, Wright suggested that the main evolutionary force driving the genetic and molecular properties of these systems was strong negative frequency-dependent selection acting on pollination success. The empirical observation of high allelic diversity at the self-incompatibility locus in several species, followed by the discovery of very high molecular divergence among alleles in all plant families where the locus has been identified, supported Wright's initial theoretical predictions as well as many of its later developments. In the last decade, however, advances in the molecular characterization of the incompatibility reaction and in the analysis of allelic frequencies and allelic divergence from natural populations have stimulated new theoretical investigations that challenged some important assumptions of Wright's model of gametophytic self-incompatibility. We here review some of these recent empirical and theoretical advances that investigated: (i) the hypothesis that S-alleles are selectively equivalent, and the evolutionary consequences of genetic interactions between alleles; (ii) the occurrence of frequency-dependent selection in female fertility; (iii) the evolutionary genetics of self-incompatibility systems in subdivided populations; (iv) the evolutionary implications of the self-incompatibility locus's genetic architecture; and (v) of its interactions with the genomic environment.     

Genetics of mosquitoes

Beginning in the mid-1950s, much progress has been made in studying various aspects of the genetics of mosquitoes, particularly involving several species of three principal genera,Aedes, Culex andAnopheles, that transmit important human diseases. Here I discuss selected areas of research involving formal genetics; genome structure, organization and evolution at the interspecific and intraspecific level; and evolutionary genetics of theAedes scutellaris group. Information and insights gained from in-depth analyses of these areas, particularly transmission genetics, cytogenetics and genetics of chromosomal rearrangements, and of mutagen-induced sexual sterility, have proved invaluable for the development of the theory and evaluation of feasibility of genetic control of natural populations. As a result, mosquitoes represent some of the best studied taxa at various levels of genetic organization. Recent developments in molecular genetics offer exciting possibilities for extension of these concepts.     

IS6110 Transposition and Evolutionary Scenario of the Direct Repeat Locus in a Group of Closely Related Mycobacterium tuberculosis Strains

In recent years, various polymorphic loci and multicopy insertion elements have been discovered in the Mycobacterium tuberculosis genome, such as the direct repeat (DR) locus, the major polymorphic tandem repeats, the polymorphic GC-rich repetitive sequence, IS6110, and IS1081. These, especially IS6110 and the DR locus, have been widely used as genetic markers to differentiate M. tuberculosis isolates and will continue to be so used, due to the conserved nature of the genome of M. tuberculosis. However, little is known about the processes involved in generating these or of their relative rates of change. Without an understanding of the biological characteristics of these genetic markers, it is difficult to use them to their full extent for understanding the population genetics and epidemiology of M. tuberculosis. To address these points, we identified a cluster of 7 isolates in a collection of 101 clinical isolates and investigated them with various polymorphic genetic markers, which indicated that they were highly related to each other. This cluster provided a model system for the study of IS6110 transposition, evolution at the DR locus, and the effects of these on the determination of evolutionary relationships among M. tuberculosis strains. Our results suggest that IS6110 restriction fragment length polymorphism patterns are useful in grouping closely related isolates together; however, they can be misleading if used for making inferences about the evolutionary relationships between closely related isolates. DNA sequence analysis of the DR loci of these isolates revealed an evolutionary scenario, which, complemented with the information from IS6110, allowed a reconstruction of the evolutionary steps and relationships among these closely related isolates. Loss of the IS6110 copy in the DR locus was noted, and the mechanisms of this loss are discussed.     

Adaptive radiation in microbial microcosms

It has often been argued that evolutionary diversification is the result of divergent natural selection for specialization on alternative resources. I provide a comprehensive review of experiments that examine the ecology and genetics of resource specialization and adaptive radiation in microbial microcosms. In these experiments, resource heterogeneity generates divergent selection for specialization on alternative resources. At a molecular level, the evolution of specialization is generally attributable to mutations that de-regulate the expression of existing biosynthetic and catabolic pathways. Trade-offs are associated with the evolution of resource specialization, but these trade-offs are often not the result of antagonistic pleiotropy. Replicate adaptive radiations result in the evolution of a similar assemblage of specialists, but the genetic basis of specialization differs in replicate radiations. The implications of microbial selection experiments for evolutionary theory are discussed and future directions of research are proposed.     

植物分子群体遗传学研究动态

分子群体遗传学是当代进化生物学研究的支柱学科, 也是遗传育种和关于遗传关联作图和连锁分析的基础理论学科。分子群体遗传学是在经典群体遗传的基础上发展起来的, 它利用大分子主要是DNA序列的变异式样来研究群体的遗传结构及引起群体遗传变化的因素与群体遗传结构的关系, 从而使得遗传学家能够从数量上精确地推知群体的进化演变, 不仅克服了经典的群体遗传学通常只能研究群体遗传结构短期变化的局限性, 而且可检验以往关于长期进化或遗传系统稳定性推论的可靠程度。同时, 对群体中分子序列变异式样的研究也使人们开始重新审视达尔文的以“自然选择”为核心的进化学说。到目前为止, 分子群体遗传学已经取得长足的发展, 阐明了许多重要的科学问题, 如一些重要农作物的DNA多态性式样、连锁不平衡水平及其影响因素、种群的变迁历史、基因进化的遗传学动力等, 更为重要的是, 在分子群体遗传学基础上建立起来的新兴的学科如分子系统地理学等也得到了迅速的发展。文中综述了植物分子群体遗传研究的内容及最新成果。     

Molecular dating in the genomic era

The comparison of DNA and protein sequences of extant species might be informative for reconstructing the chronology of evolutionary events on Earth. A phylogenetic tree inferred from molecular data directly depicts the evolutionary affinities of species and indirectly allows estimating the age of their origin and diversification. Molecular dating is achieved by assuming the molecular clock hypothesis, i.e., that the rate of change of nucleotide and amino acid sequences is on average constant over geological time. If paleontological calibrations are available, then absolute divergence times of species can be estimated. However, three major difficulties potentially hamper molecular dating : (1) a limited sample of genes and organisms, (2) a limited number of fossil references, and (3) pervasive variations of molecular evolutionary rates among genomes and species. To circumvent these problems, different solutions have been recently proposed. Larger data sets are built with more genes and more species sampled through the mining of an increasing number of genomes. Moreover, independent key fossils are identified to calibrate molecular clocks, and the uncertainty on their age is integrated in subsequent analyses. Finally, models of molecular rate variations are constructed, and incorporated in the so-called relaxed molecular clock approaches. As an illustration of these improvements, we mention that the debated age of the animal (bilaterian metazoans) diversification may have occurred between 642-761 million years ago (Mya), roughly 100 Ma before the Cambrian explosion. Among mammals, the initial diversification of major placental groups may have taken place around 100 Mya, well before the Cretaceous/Tertiary boundary marking the extinction of dinosaurs.     

基于DNA分子的现代人起源研究35年回顾与展望

1983年,有学者首次发表现代人线粒体DNA进化树,认为现代人可能起源自亚洲。1987年,又有学者按照分子钟假说得到线粒体在10-20万年前出自非洲的推论。随后,以分子钟为前提的Y染色体和常染色体DNA研究也支持了出非洲的结论,该结论逐渐成为分子进化领域的主流理论。2010年,对尼安德特人常染色体基因组的研究指出其对现代人有遗传贡献,这颠覆了人们先前关于现代人只来源自非洲,其他大洲的当地古人被完全取代的认知。目前,单地区起源说已经被修正为同化说。尽管学界对非洲人遗传多样性最高这一现象有共识,但是对该现象的不同解读却可以得出两种迥然不同的结果,现代人出亚洲说和出非洲说。大量研究证实基因组的大部分序列是有功能的,并处在遗传变异水平的饱和态,这质疑了中性理论以及由它推导的现代人出非洲说的合理性,而中性理论的提出恰恰是用来解释并非普遍存在的分子钟的。近年来已经有研究者从新理论的角度解读遗传多样性的饱和态和线性态,人们对现代人起源的认识将会进一步加深完善。