The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

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Initial sequencing and analysis of the human genome.

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

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

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

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Initial sequencing and comparative analysis of the mouse genome.

Do essential genes evolve slowly

The evolutionary forces that produced the canonical genetic code before the last universal ancestor remain obscure. One hypothesis is that the arrangement of amino acid/codon assignments results from selection to minimize the effects of errors (e.g., mistranslation and mutation) on resulting proteins. If amino acid similarity is measured as polarity, the canonical code does indeed outperform most theoretical alternatives. However, this finding does not hold for other amino acid properties, ignores plausible restrictions on possible code structure, and does not address the naturally occurring nonstandard genetic codes. Finally, other analyses have shown that significantly better code structures are possible. Here, we show that if theoretically possible code structures are limited to reflect plausible biological constraints, and amino acid similarity is quantified using empirical data of substitution frequencies, the canonical code is at or very close to a global optimum for error minimization across plausible parameter space. This result is robust to variation in the methods and assumptions of the analysis. Although significantly better codes do exist under some assumptions, they are extremely rare and thus consistent with reports of an adaptive code: previous analyses which suggest otherwise derive from a misleading metric. However, all extant, naturally occurring, secondarily derived, nonstandard genetic codes do appear less adaptive. The arrangement of amino acid assignments to the codons of the standard genetic code appears to be a direct product of natural selection for a system that minimizes the phenotypic impact of genetic error. Potential criticisms of previous analyses appear to be without substance. That known variants of the standard genetic code appear less adaptive suggests that different evolutionary factors predominated before and after fixation of the canonical code. While the evidence for an adaptive code is clear, the process by which the code achieved this optimization requires further attention.

/pdf/early-fixation-of-an-optimal-genetic-code-4yftlw5ngo.pdf

Early Fixation of an Optimal Genetic Code

As the efficacy of natural selection is expected to be a function of population size, in humans it is usually presumed that selection is a weak force and hence that gene characteristics are mostly determined by stochastic forces. In contrast, in species with large population sizes, selection is expected to be a much more effective force. Evidence for this has come from examining how genic parameters vary with expression level, which appears to determine many of a gene's features, such as codon bias, amino acid composition, and size. However, not until now has it been possible to examine whether human genes show the signature of selection mediated by expression level. Here, then, to investigate this issue, we gathered expression data for >10,000 human genes from public data sets obtained by different technologies (SAGE and high-density oligonucleotide chip arrays) and compared them with gene parameters. We find that, even after controlling for regional effects, highly expressed genes code for smaller proteins, have less intronic DNA, and higher codon and amino acid biases. We conclude that, contrary to the usual supposition, human genes show signatures consistent with selection mediated by expression level.

/pdf/the-signature-of-selection-mediated-by-expression-on-human-2itlm7pf0t.pdf

The Signature of Selection Mediated by Expression on Human Genes

It is common enough to read a paper that uses genome-sequence data to make conclusions about how an organism lives. Less common is the approach used by Pal et al. who have generated gene networks for a group of related organisms with similar lifestyles, and used those to infer gene content of another member of the group. With the genome of E. coli as starting point, they predicted the metabolism of Buchnera, an intracellular symbiont with a heavily reduced genome, that was derived from an ancestor of E. coli. This work has implications for the search for a ‘minimal genome’, and already indicates that the concept of a ‘non-essential gene’ can be spurious, as a gene can easily become essential in changing genomic contexts. Rather than using genome sequence data to make conclusions about how an organism lives, the reverse approach can be adopted — using gene networks generated for a group of related organisms with similar lifestyles to infer the gene content of another member of the group. It is possible to infer aspects of an organism's lifestyle from its gene content1. Can the reverse also be done? Here we consider this issue by modelling evolution of the reduced genomes of endosymbiotic bacteria. The diversity of gene content in these bacteria may reflect both variation in selective forces and contingency-dependent loss of alternative pathways. Using an in silico representation of the metabolic network of Escherichia coli, we examine the role of contingency by repeatedly simulating the successive loss of genes while controlling for the environment. The minimal networks that result are variable in both gene content and number. Partially different metabolisms can thus evolve owing to contingency alone. The simulation outcomes do preserve a core metabolism, however, which is over-represented in strict intracellular bacteria. Moreover, differences between minimal networks based on lifestyle are predictable: by simulating their respective environmental conditions, we can model evolution of the gene content in Buchnera aphidicola and Wigglesworthia glossinidia with over 80% accuracy. We conclude that, at least for the particular cases considered here, gene content of an organism can be predicted with knowledge of its distant ancestors and its current lifestyle.

/pdf/chance-and-necessity-in-the-evolution-of-minimal-metabolic-42z1ufqh20.pdf

Chance and necessity in the evolution of minimal metabolic networks

Two types of male-killing cytoplasmic gene are distinguished by their time of action. Early male killers strike embryos, whereas late killers, so far only observed in mosquitoes, kill fourth instar larvae. Maternal inheritance of cytoplasmic factors underlies the sex bias in mortality in both instances. However, the evolutionary logic of early and late killing is, it is argued, otherwise different. Early male killing is interpreted in terms of kin selection. The death of male embryos early on allows resources (food or space) to be redistributed to the surviving females. A simple model relying on the redirection of resources after male death indicates that so long as a more than critical proportion of 9freed’ resources goes to females containing clonal relatives of the male-killing cytoplasmic gene, then that gene can invade and go to an equilibrium. This equilibrium is significant in that it allows a population to avoid extinction prior to the evolution of a nuclear repressor gene. The distribution of male killing is discussed in the light of these findings. The late male-killing microsporidians of mosquitoes differ from early male killing factors in possessing horizontal, as well as vertical, transmission between generations. It is argued that to maximize the efficiency of horizontal transmission it is in the interests of the microsporidians to maximize their number by waiting for the host to grow before killing it. Not all microsporidians kill only the male mosquito, some also kill the female. The variety of mosquito-microsporidian pathologies is interpreted by considering a trade-off between the efficiency of vertical against horizontal transmission. A review of possible incidences of cytoplasmic male killing is presented.

Laurence D. Hurst

Papers

Do essential genes evolve slowly

Early Fixation of an Optimal Genetic Code

The Signature of Selection Mediated by Expression on Human Genes

Chance and necessity in the evolution of minimal metabolic networks

The Incidences and Evolution of Cytoplasmic Male Killers