Genome sequencing of environmental Escherichia coli expands understanding of the ecology and speciation of the model bacterial species

Defining bacterial species remains a challenging problem even for the model bacterium Escherichia coli and has major practical consequences for reliable diagnosis of infectious disease agents and regulations for transport and possession of organisms of economic importance. E. coli traditionally is thought to live within the gastrointestinal tract of humans and other warm-blooded animals and not to survive for extended periods outside its host; this understanding is the basis for its widespread use as a fecal contamination indicator. Here, we report the genome sequences of nine environmentally adapted strains that are phenotypically and taxonomically indistinguishable from typical E. coli (commensal or pathogenic). We find, however, that the commensal genomes encode for more functions that are important for fitness in the human gut, do not exchange genetic material with their environmental counterparts, and hence do not evolve according to the recently proposed fragmented speciation model. These findings are consistent with a more stringent and ecologic definition for bacterial species than the current definition and provide means to start replacing traditional approaches of defining distinctive phenotypes for new species with omics-based procedures. They also have important implications for reliable diagnosis and regulation of pathogenic E. coli and for the coliform cell-counting test.     

Molecular coevolution of a sex pheromone and its receptor triggers reproductive isolation in Schizosaccharomyces pombe

The diversification of sex pheromones is regarded as one of the causes of prezygotic isolation that results in speciation. In the fission yeast Schizosaccharomyces pombe, the molecular recognition of a peptide pheromone by its receptor plays an essential role in sexual reproduction. We considered that molecular coevolution of a peptide-mating pheromone, M factor, and its receptor, Map3, might be realized by experimentally diversifying these proteins. Here, we report the successful creation of novel mating-type pairs by searching for map3 suppressor mutations that rescued the sterility of M-factor mutants that were previously isolated. Several strong suppressors were found to also recognize WT M factor. The substituted residues of these Map3 suppressors were mapped to F204, F214, and E249, which are likely to be critical residues for M-factor recognition. These critical residues were systematically substituted with each of the other amino acids by in vitro mutagenesis. Ultimately, we successfully obtained three novel mating-type pairs constituting reproductive groups. These novel mating-type pairs could not conjugate with WT maters. Furthermore, no flow of chromosomally integrated drug-resistance genes occurred between the novel and the WT mating pairs, showing that each experimentally created reproductive group [e.g., M factor(V5H) and Map3(F214H)] was isolated from the WT group. In conclusion, we have succeeded in creating an artificial reproductive group that is isolated from the WT group. In keeping with the biological concept of species, the artificial reproductive group is a new species.Speciation is the most critical step in evolution (1). A new species branches off from an original species when a group of individuals is isolated reproductively (termed “reproductive isolation”) (2). Chemical communication between the two sexes is important in both attracting individuals of the opposite sex and the courtship reaction. Pheromone diversification may be a possible mechanism underlying reproductive isolation.Female-attracting peptide pheromones of newts are providing a promising means to explore this mechanism. A decapeptide called sodefrin was first identified during the analysis of a cDNA library of the abdominal gland of the red-bellied newt Cynops pyrrhogaster (3, 4). A closely related newt, the sword-tailed newt Cynops ensicauda, produces a similar peptide pheromone named Silefrin (5). Interestingly, a sodefrin variant, aonirin, was found in the Nara area of Japan; 1 of 10 amino acids in aonirin differs from those in sodefrin, the prototype peptide (6). This variant peptide was found to not be effective in attracting females in the Niigata and Chiba areas of Japan (7). It was, thus, speculated that altering the primary structure of the female-attracting peptide of the red-bellied newt and coevolution of the corresponding receptor protein may lead to reproductive isolation. To verify this speculation, we are interested in artificially altering a pheromone and its receptor, thereby mimicking coevolution in nature, by using a genetically amenable model organism, the fission yeast Schizosaccharomyces pombe.

Table 1.

Primary structure of peptide pheromones in some red-bellied newts (Cynops sp.) and fission yeasts (Schizosaccharomyces sp.)

The evolution of courtship behaviors through the origination of a new gene in Drosophila

New genes can originate by the combination of sequences from unrelated genes or their duplicates to form a chimeric structure. These chimeric genes often evolve rapidly, suggesting that they undergo adaptive evolution and may therefore be involved in novel phenotypes. Their functions, however, are rarely known. Here, we describe the phenotypic effects of a chimeric gene, sphinx, that has recently evolved in Drosophila melanogaster. We show that a knockout of this gene leads to increased male-male courtship in D. melanogaster, although it leaves other aspects of mating behavior unchanged. Comparative studies of courtship behavior in other closely related Drosophila species suggest that this mutant phenotype of male-male courtship is the ancestral condition because these related species show much higher levels of male-male courtship than D. melanogaster. D. melanogaster therefore seems to have evolved in its courtship behaviors by the recruitment of a new chimeric gene.     

Pheromone evolution and sexual behavior in Drosophila are shaped by male sensory exploitation of other males

Animals exhibit a spectacular array of traits to attract mates. Understanding the evolutionary origins of sexual features and preferences is a fundamental problem in evolutionary biology, and the mechanisms remain highly controversial. In some species, females choose mates based on direct benefits conferred by the male to the female and her offspring. Thus, female preferences are thought to originate and coevolve with male traits. In contrast, sensory exploitation occurs when expression of a male trait takes advantage of preexisting sensory biases in females. Here, we document in Drosophila a previously unidentified example of sensory exploitation of males by other males through the use of the sex pheromone CH503. We use mass spectrometry, high-performance liquid chromatography, and behavioral analysis to demonstrate that an antiaphrodisiac produced by males of the melanogaster subgroup also is effective in distant Drosophila relatives that do not express the pheromone. We further show that species that produce the pheromone have become less sensitive to the compound, illustrating that sensory adaptation occurs after sensory exploitation. Our findings provide a mechanism for the origin of a sex pheromone and show that sensory exploitation changes male sexual behavior over evolutionary time.Sexual selection is widely regarded as an important mechanism for the origin of new traits and species. Darwin first proposed that the elaboration of male secondary sexual traits is driven by female preferences (1, 2). This concept has been refined by models suggesting that females select male traits that indicate genetic quality or confer direct reproductive benefits (3–7). In contrast, sensory exploitation occurs when expression of a male trait takes advantage of preexisting sensory biases in females (8). In this case, female preference does not coevolve with the male trait but rather precedes it. In one of the first examples documenting sensory exploitation, female Physalaemus coloradorum frogs were shown to prefer male calls that contain a low-frequency “chuck” component despite the absence of this feature in calls from conspecifics. The sensory bias for chucks was shown to have its mechanistic basis in the tuning properties of the inner ear, a physiological feature that predated the appearance of chucks (9). Similarly, female platyfish exhibit a preference for males with swordtails despite the absence of swordtails in male platyfish. Females consistently chose to spend more time with conspecific males exhibiting an artificially attached plastic sword (10). In both these examples, female preference predates expression of the trait. Sensory exploitation has since been documented for numerous other visual cues, across a diversity of taxa (11–14). In each case, females prefer traits that are not found naturally in their own species but appear in males of other species. Moreover, both the sensory bias and behavioral response to the trait already were present before expression of the trait.Pheromones are taste and olfactory cues that, in many species, play an important role in mate selection (15). As with courtship cues detected by other sensory modalities, pheromones are shaped by sexual selection and, thus, may exhibit enormous structural diversity and exquisite stereochemical specificity. In insects, exogenously secreted lipids advertise mating status, availability, and reproductive fitness (16). In some cases, male pheromones serve as a nuptial gift, thus providing direct reproductive benefits to females and offspring in the form of either nutritive or defensive compounds (17). Little is known, however, about the mechanisms underlying the diversification and the origin of chemical specificity. Here, we provide an example of a pheromone that has evolved from sensory exploitation. In Drosophila melanogaster, CH503 [formally, (3R,11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol; Fig. 1A] functions as an antiaphrodisiac (18). The pheromone is secreted in the anogenital region, is transferred to females during mating, and suppresses courtship from males. Our findings indicate CH503 evolved from males exploiting the preexisting sensory biases of other males to gain mating advantage by limiting access to females. Moreover, the use of CH503 has altered male sexual behavior over evolutionary time such that males have adapted by becoming less sensitive to the pheromone.Open in a separate windowFig. 1.Characterization of CH503 expression in Drosophila. (A) Chemical structure of CH503 and representative UV-LDI mass spectra measured from the male anogenital region of different Drosophila species. Each spectrum is recorded from a single fly. Signals corresponding to the mass-to-charge ratio (m/z) for cVA (m/z 349.24) and CH503 (m/z 503.38) were detected in D. melanogaster, D. simulans, D. yakuba, D. sechellia, and D. ananassae. No signal for CH503 was detected from D. willistoni, D. mojavensis, or D. virilis. Potassium-bearing molecular compounds [M+K]⁺ constitute the major ion species in all cases. (B) The HPLC chromatogram shows distinct retention times (RT) for each of the eight synthetic CH503 stereoisomers following derivatization. HPLC analysis of derivatized CH503 isolated from D. simulans, D. yakuba, and D. sechellia reveals that (3R,11Z,11Z)-CH503 is the only expressed stereoisomer. The retention times for the major peaks are noted in each chromatogram. The compound isolated from D. ananassae has the same m/z and elemental composition as CH503 but a different structure.     

胃粘膜异型增生C-erbB-2基因表达及其癌变率的研究

目的　利用免疫组化的方法探索癌前病变到癌这一过程的转化 ,探索C erbB 2基因在这一转化过程的重要作用以及在胃癌早期诊断中的意义。方法　采用胃镜活检标本 ,选择胃粘膜异型增生的病例 ,资料完整 ,有随访结果 ,分出癌变组与未癌变组 ,利用免疫组化的方法检测C erbB 2基因蛋白表达情况。结果　正常胃粘膜、轻、中、重度异型增生的癌变率分别为 0、3 4%、10 7%、16 7%,随着异型增生的程度增加其癌变率增加。未癌变组C erbB 2蛋白表达的阳性率分别为 0、5 6 1%、72 %、83 3%,癌变组分别 0、5 0 %、33 3%、2 0 %,中、重度异型增生未癌变与癌变组间差异有显著性 (P <0 0 5 )。在癌变组C erbB 2蛋白表达的阳性率降低 ,而癌变率增加。结论　异型增生是一种重要的癌前病变 ,C erbB 2基因的变异在胃癌的发生、发展中起重要作用 ,对异型增生胃粘膜进行C erbB 2基因检测有助于胃癌的早期诊断和治疗。     

A triallelic system of S5 is a major regulator of the reproductive barrier and compatibility of indica-japonica hybrids in rice

Hybrid sterility is a major form of postzygotic reproductive isolation. Although reproductive isolation has been a key issue in evolutionary biology for many decades in a wide range of organisms, only very recently a few genes for reproductive isolation were identified. The Asian cultivated rice (Oryza sativa L.) is divided into two subspecies, indica and japonica. Hybrids between indica and japonica varieties are usually highly sterile. A special group of rice germplasm, referred to as wide-compatibility varieties, is able to produce highly fertile hybrids when crossed to both indica and japonica. In this study, we cloned S5, a major locus for indica-japonica hybrid sterility and wide compatibility, using a map-based cloning approach. We show that S5 encodes an aspartic protease conditioning embryo-sac fertility. The indica (S5-i) and japonica (S5-j) alleles differ by two nucleotides. The wide compatibility gene (S5-n) has a large deletion in the N terminus of the predicted S5 protein, causing subcellular mislocalization of the protein, and thus is presumably nonfunctional. This triallelic system has a profound implication in the evolution and artificial breeding of cultivated rice. Genetic differentiation between indica and japonica would have been enforced because of the reproductive barrier caused by S5-i and S5-j, and species coherence would have been maintained by gene flow enabled by the wide compatibility gene.     

烧伤患者创面感染金黄色葡萄球菌分离株耐药性及流行病学分析

目的对河北地区烧伤患者创面分离的120株金黄色葡萄球菌进行mecA和SCCmec检测分析MRSA耐药机制,为临床合理用药提供依据。方法在2009~2013年收治的烧伤患者创面中分离的120株金黄色葡萄球菌,采用头孢西丁纸片法进行MRSA筛选,对mecA基因,SCCmec和spa基因进行PCR扩增以及分型。结果 120株金黄色葡萄球菌中有74株为MRSA,占61.7%。药敏试验显示,MRSA对16种临床常见抗生素耐药率,超过85%的有7种,依次为苯唑西林（98.6%）,青霉素（96.0%）,环丙沙星（94.6%）,阿莫西林和头孢唑林（89.2%）,亚胺培南（87.8%）,庆大霉素（85.1%）,另有1株对万古霉素耐药。结论本组金黄色葡萄球菌MRSA检出率较高,并表现出较高的耐药性。MRSA具有的多重耐药性mecA基因密切关系。     

Ki-ras gene mutations are invariably present in low-grade mucinous tumors of the vermiform appendix

Abstract

Objective. Low-grade mucinous tumors of the appendix appear to have a simple histological structure. Paradoxically, reports have suggested a greater frequency of Ki-ras gene mutation in these lesions than in more complex lesions such as benign colonic adenomas and carcinomas. We assessed several molecular genetic changes, including Ki-ras gene mutations, in a large series of low-grade mucinous tumors of the appendix. Material and methods. We retrospectively ascertained low-grade mucinous tumors of the appendix from computerized pathology records. Extracted DNA was analyzed for APC and DCC gene loss of heterozygosity, microsatellite instability and for the presence of Ki-ras gene mutation using standard molecular techniques. Controls consisted of normal appendices, other appendiceal neoplasms, and ovarian mucinous cystadenomas. Results. A total of 31 low-grade appendiceal mucinous tumors were identified. All were microsatellite stable and none demonstrated loss of heterozygosity for the APC or DCC genes. By contrast, all 31 lesions contained a Ki-ras gene mutation. Conclusions. The presence of a Ki-ras gene mutation in all lesions, with no other molecular changes identified, strongly suggests a possible etiological role of the Ki-ras mutation in the development of this particular lesion of the appendix. Based on other work regarding intestinal bacteria, we hypothesize a relationship between chronic inflammation of the appendix from bacterial overgrowth and Ki-ras gene mutation.     

HLA-A and HLA-B genes are involved in the pathogenesis of IBS

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder. The pathogenesis of IBS has not yet been fully elucidated, and the relationship between human leukocyte antigen (HLA) class I molecules and IBS is not clear. The present case-control study investigated the correlation between HLA-A and HLA-B genes and IBS. Peripheral blood samples were collected from 102 IBS patients and 108 healthy volunteers at Nanning First People’s Hospital. DNA was extracted using a routine procedure, and HLA-A and HLA-B gene polymorphisms were identified by polymerase chain reaction with sequence-specific primers to determine the genotype and distribution frequency of HLA-A and HLA-B in IBS patients and healthy controls. Susceptibility and protective genes for IBS were identified using univariate and multivariate analyses. The frequency of HLA-A11 gene expression in the IBS group was significantly higher than that in the healthy control group, while the frequencies of HLA-A24, 26, and 33 gene expression were significantly higher in the healthy control group than in the IBS group (all P < .05). The frequencies of HLA-B56 and 75 (15) gene expression in the IBS group were significantly higher than those in the healthy control group, while the frequencies of HLA-B46 and 48 gene expression were significantly higher in the healthy control group than in the IBS group (all P < .05). Genes that may be related to the prevalence of IBS were included in the multivariate logistic regression, and the results suggested that the HLA-B75 (15) gene is a susceptibility gene for IBS (P = .031, odds ratio [OR] = 2.625, 95% confidence interval [CI]: 1.093–6.302), while the HLA-A24 (P = .003, OR = 0.308, 95% CI: 0.142–0.666), A26 (P = .009, OR = 0.162, 95% CI: 0.042–0.629), A33 (P = .012, OR = 0.173, 95% CI: 0.044–0.679), and B48 (P = .008, OR = 0.051, 95% CI: 0.006–0.459) genes are protective genes for IBS.     

Molecular and phylogenetic analysis of matrix gene of avian influenza viruses isolated from wild birds and live bird markets in the USA

Please cite this paper as: Chander et al. (2012) Molecular and phylogenetic analysis of matrix gene of avian influenza viruses isolated from wild birds and live bird markets in the USA. Influenza and Other Respiratory Viruses 7(4), 513–520. Background  Wild birds are the natural hosts for influenza A viruses (IAVs) and provide a niche for the maintenance of this virus. Objectives  This study was undertaken to analyze nucleotide sequences of the matrix (M) gene of AIVs isolated from wild birds and live bird markets (LBMs) to index the changes occurring in this gene. Methods  M‐gene of 229 avian influenza virus (AIV) isolates obtained from wild birds and LBMs was amplified and sequenced. Full‐length sequences (∼900 nt.) thus obtained were analyzed to identify changes that may be associated with resistance to adamantanes. Phylogenetic analysis of all sequences was performed using clustalw, and evolutionary distances were calculated by maximum composite likelihood method using mega (ver. 5.0) software. Results  Twenty‐seven different viral subtypes were represented with H3N8 being the most dominant subtype in wild birds and H7N2 being the predominant subtype among isolates from LBMs. Phylogenetic analysis of the M‐gene showed a high degree of nucleotide sequence identity with US isolates of AIVs but not with those of Asian or European lineages. While none of the isolates from wild birds had any antiviral resistance–associated mutations, 17 LBM isolates carried polymorphisms known to cause reduced susceptibility to antiviral drugs (adamantanes). Of these 17 isolates, 16 had S31N change and one isolate had V27A mutation. Conclusions  These results indicate independent evolution of M‐gene in the absence of any antiviral drugs leading to mutations causing resistance indicating the need for continued active surveillance of AIVs.     

原核细胞microRNA特性及其作用机制研究进展

microRNA为一类非编码小RNA,主要通过其种子序列(seed sequence,SS)与靶mRNA位于5′端的SS结合序列特异性结合后抑制靶mRNA转录或降解靶mRNA,从而在转录后水平负调控靶基因表达。microRNA首先发现于秀丽隐杆线虫(Caenorhabditis elegans),此后发现各种真核细胞均存在大量各种microRNA。真核细胞首先转录出microRNA前体,经剪切后成为21~23nt有功能的microRNA,大多与靶mRNA的3′端序列结合后引起靶mRNA翻译抑制或降解。近年不少细菌等原核细胞microRNA被发现,但原核细胞microRNA不需剪切即有活性,大小为50~400nt,其特性、作用位点和机制等也与真核细胞有一定差异。本文简要介绍真核和原核细胞基因表达调控主要机制、microRNA特点及其调控基因表达的机制,以期为深入研究原核细胞型病原微生物基因表达调控与致病机制奠定基础。     

From the Cover: Dynamic evolutionary change in post-Paleozoic echinoids and the importance of scale when interpreting changes in rates of evolution

How ecological and morphological diversity accrues over geological time has been much debated by paleobiologists. Evidence from the fossil record suggests that many clades reach maximal diversity early in their evolutionary history, followed by a decline in evolutionary rates as ecological space fills or due to internal constraints. Here, we apply recently developed methods for estimating rates of morphological evolution during the post-Paleozoic history of a major invertebrate clade, the Echinoidea. Contrary to expectation, rates of evolution were lowest during the initial phase of diversification following the Permo-Triassic mass extinction and increased over time. Furthermore, although several subclades show high initial rates and net decreases in rates of evolution, consistent with “early bursts” of morphological diversification, at more inclusive taxonomic levels, these bursts appear as episodic peaks. Peak rates coincided with major shifts in ecological morphology, primarily associated with innovations in feeding strategies. Despite having similar numbers of species in today’s oceans, regular echinoids have accrued far less morphological diversity than irregular echinoids due to lower intrinsic rates of morphological evolution and less morphological innovation, the latter indicative of constrained or bounded evolution. These results indicate that rates of evolution are extremely heterogenous through time and their interpretation depends on the temporal and taxonomic scale of analysis.Assessing how rates of morphological evolution have changed over geological time has been a major research goal of evolutionary paleobiologists since Westoll’s classic study of lungfish evolution (1). A common pattern to emerge from the fossil record is that many clades reach maximal morphological diversity early in their evolutionary history (2–4). This sort of pattern could be the result of an “early burst” of morphological diversification as taxa diverge followed by a slow-down in rates as ecological space becomes filled (5, 6). Internal constraint or long-term selective pressures could also limit overall disparity, leading to a slowdown in the rate of new trait acquisition over time (7, 8). However, only a small proportion of fossil disparity studies have also assessed changes in rates of evolution within lineages (e.g., along phylogenetic branches) thereby providing a more nuanced understanding of how this disparity came about (e.g., refs. 9–13). Simultaneously, decreasing rates in trait evolution have been difficult to detect using phylogenetic comparative data of extant taxa, because of low statistical power (14, 15), loss of signal through extinction (16), and inaccuracies in reconstructing ancestral nodes (17). Here we take advantage of recently developed methods for directly estimating per-lineage-million-year rates of evolution from phylogenies with both fossil and living taxa to test whether declining rates characterize the evolutionary history of a major clade of marine invertebrates, the echinoids.Since originating some 265 million years ago (18, 19), crown group echinoids have evolved to become ecologically and morphologically diverse in today’s oceans, and are an important component of both past and present marine ecosystems (e.g., refs. 20–22). However, analysis of how this diversity arose has either been based on taxonomic counts (e.g., ref. 23) or has adopted a morphometric approach where the requirement of a homologous set of landmarks limits taxonomic, temporal, and geographic scope (e.g., ref. 24). We use a discrete-character-based approach and a recent taxonomically comprehensive analysis of post-Paleozoic echinoids as our phylogenetic framework (25). This tree is almost entirely resolved (SI Appendix, Fig. S1) and branches may be scaled using the first appearance of each taxon in the fossil record (SI Appendix, Table S1). We tabulated the number of character state changes that occurred along each branch within ∼10-million-year time intervals spanning the Permian and post-Paleozoic (SI Appendix, Table S2), and divided this by the summed duration of branch lengths to compute a time series of per-lineage-million-year rates of morphological evolution. We accounted for uncertainty in phylogenetic structure, uncertainty in the timing of the first appearance of taxa, and uncertainty in the timing of character changes along each branch using a randomization approach (12). We also estimated rates within subclades, corroborating our findings by using likelihoods tests to determine whether some branches had higher rates than expected given rates across the entire tree. Finally, we compared rates of evolution through time with the structure of diversification within a character-defined morphospace, and looked for evidence of differences in evolutionary modes among subclades. The pattern that emerges is one of dynamic evolutionary change through time: Both rates and patterns of evolution vary temporally and across subclades, such that the overall pattern depends highly on the temporal and taxonomic scale of the analysis.     

Contrasting the Practices of Virus Isolation and Characterization between the Early Period in History and Modern Times: The Case of Japanese Encephalitis Virus

Japanese encephalitis is a serious disease transmitted by mosquitoes. With its recent spread beyond the traditional territory of endemicity in Asia, the magnitude of global threat has increased sharply. While much of the current research are largely focused on changing epidemiology, molecular genetics of virus, and vaccination, little attention has been paid to the early history of virus isolation and phenotypic characterization of this virus. In this review, using this piece of history as an example, I review the transition of the concept and practice of virus isolation and characterization from the early period of history to modern times. The spectacular development of molecular techniques in modern times has brought many changes in practices as well as enormous amount of new knowledge. However, many aspects of virus characterization, in particular, transmission mechanism and host relationship, remain unsolved. As molecular techniques are not perfect in all respects, beneficial accommodation of molecular and biologic data is critically important in many branches of research. Accordingly, I emphasize exercising caution in applying only these modern techniques, point out unrecognized communication problems, and stress that JE research history is a rich source of interesting works still valuable even today and waiting to be discovered.     

The evolution of factor VIIa in the treatment of bleeding in haemophilia with inhibitors

The use of activated factor VII (FVIIa) for the treatment of bleeding events in haemophilia patients with inhibitors was first reported over 30 years ago. Since then clinical trials, registries, case series, real‐world experience and an understanding of its mechanism of action have transformed what was originally a scientific curiosity into one of the major treatments for inhibitor patients, with innovative therapeutic regimens, dose optimization and individualized care now widely practiced. Given current understanding and use, it might be easy to forget the years of clinical research that led up to this point; in this review, we lay out changes based on broad eras of rFVIIa use. These eras cover the original uncertainty associated with dosing, efficacy and safety; the transformation of care ushered in with its widespread use; and the optimization and individualization of patient care and the importance of specialized support provided by haemophilia treatment centres. Today with the introduction of novel prophylactic agents such as emicizumab, we once again find ourselves dealing with the uncertainties of how best to utilize rFVIIa and newer investigational variants such as marzeptacog alfa and eptacog beta; we hope that the experiences of the past three decades will serve as a guide for this new era of care.     

H6N6亚型禽流感病毒进化演变及跨种属传播研究进展

H6N6亚型禽流感病毒(AVI)在欧亚大陆野生鸟类和家禽中广泛流行,通过适应性突变和基因重配,其宿主范围逐渐扩大,遗传分析表明该病毒是高致病禽流感病毒H5N6的先祖之一。近年来研究证实,H6N6亚型AIV可以感染小鼠、雪雕、猪等哺乳动物,甚至在健康人群中检测到H6亚型AIV的血清特异性抗体,表明H6N6亚型禽流感病毒具有跨越物种屏障感染哺乳动物的能力,并对人类健康构成潜在威胁。本文从H6N6病毒起源、流行情况、进化演变及跨种属传播的研究进展进行综述,以期为H6N6亚型AIV的防控提供参考。     

卷曲霉素抗结核作用及耐药机制的研究进展

卷曲霉素(Capreomycin, CPM)是治疗耐多药结核病的二线注射类药物。随着临床上越来越多的使用,CPM耐药问题正逐步浮现,其作用及耐药机制尚未明确。本文针对卷曲霉素治疗结核病的作用机制、耐药机制及相关基因突变的研究进展进行综述,以供研究者参考。     

Teeth,prenatal growth rates,and the evolution of human-like pregnancy in later Homo

Evidence of how gestational parameters evolved is essential to understanding this fundamental stage of human life. Until now, these data seemed elusive given the skeletal bias of the fossil record. We demonstrate that dentition provides a window into the life of neonates. Teeth begin to form in utero and are intimately associated with gestational development. We measured the molar dentition for 608 catarrhine primates and collected data on prenatal growth rate (PGR) and endocranial volume (ECV) for 19 primate genera from the literature. We found that PGR and ECV are highly correlated (R² = 0.93, P < 0.001). Additionally, we demonstrated that molar proportions are significantly correlated with PGR (P = 0.004) and log-transformed ECV (P = 0.001). From these correlations, we developed two methods for reconstructing PGR in the fossil record, one using ECV and one using molar proportions. Dental proportions reconstruct hominid ECV (R² = 0.81, P < 0.001), a result that can be extrapolated to PGR. As teeth dominate fossil assemblages, our findings greatly expand our ability to investigate life history in the fossil record. Fossil ECVs and dental measurements from 13 hominid species both support significantly increasing PGR throughout the terminal Miocene and Plio-Pleistocene, reflecting known evolutionary changes. Together with pelvic and endocranial morphology, reconstructed PGRs indicate the need for increasing maternal energetics during pregnancy over the last 6 million years, reaching a human-like PGR (i.e., more similar to humans than to other extant apes) and ECV in later Homo less than 1 million years ago.

Life history describes the schedule and process of growth and development, otherwise known as ontogeny (1, 2). Key milestones in mammalian life history begin early in development with conception and gestation, and proceed throughout the lifespan, ending in death. The earliest stages of primate life history are intricately balanced through the maternal–infant relationship (3). Developing human embryos, like those of other primates, are entirely reliant on their gestating parent throughout prenatal development; it is the only stage of primate life history where a gestating female cannot pass on or distribute any of the metabolic or physiological burden of growing and raising offspring to other members of the social group (3–5). However, a gestating parent can receive support through the community, including through a partner, whether or not they have contributed genetic material to the offspring. This support is almost always linked to resource provisioning and protection from predators (6–8).The growing body of research on primate maternal energetics, infant growth and development, and the evolution of cognition revolves around a complex network of resource provisioning, maternal health, trophic status, locomotion, body size, infant dependency (sometimes referred to as altriciality), and social network (5, 9–17). The importance of each of these factors in the evolution of the human species is still very much under debate, largely complicated by the difficulty of assessing many of these physiological and behavioral traits in the fossil record. While a large body of research has focused on postnatal growth rates and duration in humans and other hominids (18–20), almost no research has investigated prenatal growth rates (PGRs) in the fossil record. This imbalance is due in part to the prior inability to infer such a complex life history trait from skeletal remains.Prenatal growth, the rate of embryonic and fetal growth in utero, plays a key role in establishing the trajectory of an individual’s metabolism, neurological development, and ultimate growth during their lifetime (21). Calculated as the ratio of birth weight (mass in grams) to gestation length (days) (22), mammalian species that have high rates of prenatal growth have infants that are larger at birth relative to other species with comparable lengths of gestation. In primates, gestational length is relatively similar across the phylogeny, while PGR can vary quite significantly (23, 24), suggesting that growth rate provides a key source of variation upon which primate evolution occurs.Despite the oft-repeated statement that human infants are secondarily altricial, meaning that they have most of their growing to do after they are born, humans have the highest PGR among primates (25–27). This life history distinguishes humans from even their closest living relatives (26, 28, 29). This high PGR results in human infants that are quite large at birth relative to their time of gestation, with both large neonatal body mass and brain mass compared to other primates (25, 30). Yet, despite this large body and brain mass, at birth the human infant brain is still only 30% of the size of the adult brain, a developmental characteristic that leads to a helpless infant that is highly reliant on parents and other social group members for survival (19, 31).Cooperative breeding, pair bonding, and group care have been hypothesized as critical factors in the evolution of the human brain and the helpless infant (11, 17, 21, 32–37). The helpless infant requires constant care and attention, which is provided only by the birthing parent unless they can receive some assistance. Research in nonhuman primates shows that mothers who receive assistance are better able to secure resources for themselves and their infants (30, 36, 38). As the brain is a metabolically expensive organ, resource intake is essential for infant brain growth and development (32, 39, 40). This is also true at earlier life history stages, when the fetus is developing in utero (5, 15, 28). Research in cetaceans has demonstrated that brain size in these large and highly social animals is related to PGR as well as gestational length, with growth rate dependent on maternal energetics, including metabolism, resource intake, and other physiological traits involved in gestation (41). This supports the hypothesis that PGRs are also significantly associated with adult endocranial volume (ECV) in primates, which would not be a surprising result since adult ECV is strongly correlated with neonatal ECV in primates (4). Across eutherians, large neonatal and adult relative brain size do not appear to be related to periods of accelerated brain growth during fetal development, as higher encephalization seems to be a product of slower body growth rather than an increased rate of brain growth (42). However, to our knowledge the direct correlation between PGR and adult ECV has not been previously quantified in primates, and so we test this hypothesis here.Like the brain, teeth begin to form in utero and are thus intimately associated with the developmental processes in mammalian early life history (43, 44). After birth, teeth remain linked to crucial life history landmarks, including weaning, menarche, and sexual activity through mate competition, and have thus been used extensively to reconstruct primate life histories in the fossil record (1, 29, 45–55). Considerable pleiotropy underlies dental development, with genetic and phenotypic variation in individual tooth morphology being shared with body size, craniofacial structures, and other teeth across the dental arch (43, 44, 56, 57). More recent work has demonstrated that these pleiotropic effects extend even to traits in other parts of the body, including those associated with the maternal–infant relationship, such as a lactation (58).Our previous work in callitrichids linked slow PGRs to third molar loss, providing one of the first lines of evidence that dental morphology may be directly associated with PGR in primates (59). This insight has direct bearing on humans, as third molar reduction remains one of the most distinct dental features of humans compared to other primates (60–62). A large body of work has generated hypotheses for the drivers of third molar reduction and loss in humans, which range from craniofacial reduction, to brain size increases, to changes in diet and technology, and may in fact be related to all of these morphological and behavioral evolutionary shifts; these relationships have yet to be resolved (60, 63, 64). Based on our previous work, we hypothesized that PGR has a direct quantitative relationship with both ECV and third molar reduction in humans. One of the clearest ways to investigate third molar reduction is through quantification of molar proportions (60–63).In order to test our hypothesis, we collected dental data on extant and fossil primates and calculated the molar module component (MMC), a genetically patterned trait that captures the ratio of the third to first molar length and thus third molar relative size. MMC has been genetically and phenotypically assessed in a range of catarrhine primates (57, 65), including fossil hominids (66, 67), as well as more broadly across mammals (68, 69). All of these studies demonstrate that MMC carries a strong phylogenetic signal and is not driven by dietary adaptation or body size. Given that disruptions to intrauterine growth in humans result in reduced cranial and tooth size (43, 70), the genetic mechanism underlying variation in MMC may be shared between these traits. We present here an investigation of the relationship between MMC and PGR in extant and fossil primates. Our work aims to develop methods for estimating the evolution of PGR in the hominid fossil record and thereby open a window into the evolutionary history of human gestation.One of the great challenges to human evolutionary research lies in the limitations of the fossil record. Although fossils are an essential resource that provide the only direct line into the past, the factors at play in fossilization result in a vertebrate record that is comprised almost exclusively of fossilized teeth and bones (71). Thus, in order to elucidate the evolution of human life history, researchers are tasked with the critical job of developing new methods for deducing life history details from hard tissues. Reconstructing life history in the fossil record remains a primary focus of human evolutionary studies (49, 72–74), and a large body of research has focused on the evolutionary interplay between brain size and craniodental and pelvic morphology in fossil hominids (75, 76). Considering that PGR is linked to maternal investment and ECV, a clearer understanding of PGRs in fossil hominids is invaluable to the study of the evolution of human gestation and brain size, crucial elements in life history theory. Using extant and fossil primate data, including dental metrics, PGR, and ECV, we tested the following hypotheses:

• H1)PGR is highly correlated with ECV in extant catarrhine primates.
• H2)Third molar proportions (as captured by MMC) are significantly associated with PGR and ECV in extant catarrhine primates.
• H3)Third molar proportions (as captured by MMC) can accurately predict ECV, and thus PGR, in the hominid fossil record.

By testing these hypotheses, we aimed to address two larger outstanding questions about the evolution of life history in humans:

• Q1)Have hominoid PGRs increased significantly throughout the Miocene and Plio-Pleistocene?
• Q2)When did human-like (i.e., more similar to humans than to other extant apes) PGRs first evolve?

In order to test our hypotheses and answer these essential questions about life history, we developed two models for predicting PGR (infant body mass in grams divided by gestation length in days) in the fossil record by using statistical relationships between PGR, ECV, and molar proportions (third molar length relative to first molar length, MMC) in extant catarrhines (n = 608). We present evidence that fossil PGRs can be predicted from both ECV and MMC and thus provide two methods for investigating life history in the fossil record. The relationship between ECV and PGR is extremely tight, while the dental model has more variable predictions, probably due to the impacts of derived craniofacial morphology (e.g., extreme prognathism). To check that dental proportions accurately reconstruct PGR and ECV, we validated our dental model through a quantitative comparison of predicted and observed ECV in the hominid fossil record (n = 13 species). Additionally, we statistically compared the results from both models and assessed the evolution of PGR over the last 6 million years of the hominid fossil record.