Natural selection and adaptive evolution of leptin

Leptin is an adiposity-secreted hormone that is pivotal in regulating feeding behavior,energy metabolism and body mass.The study of leptin has been of crucial importance for public health and pharmaceutical intervention given its role in obesity.Generally,leptin is highly conserved due to its functional importance.However,episodes of rapid sequence evolution and positive selection have been observed in some mammalian species,indicating that the leptin functions in these animals may have undergone adaptive modification to their environments.In this article,we review the adaptive evolution of leptin and its potential functional consequences.This review is expected to guide future research of molecular evolution and functional assays of this gene,and also to provide a theoretical foundation for the use of leptin in therapeutic applications.     

Prediction of sites under adaptive evolution in flavin-containing monooxygenases: Selection pattern revisited

Flavin-containing monooxygenase (FMO), like cytochrome P450 (CYP), is a monooxygenase that uses the reducing equivalents of NADPH to reduce one atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. Recently, it was shown that some CYP isoforms have been subject to positive selection. However, it is unknown whether the highly conserved phase I detoxification enzyme, FMO, has undergone similar positive Darwinian selection. We used maximum-likelihood models of codon substitution, evolutionary fingerprinting, and cross species comparison to investigate the occurrence of adaptive evolution in FMO sequences. We used recent genomic data from a range of species, including vertebrates and invertebrates. We present the evidence for the occurrence of adaptive evolution in mammalian FMO 3, 4, 5, and fugu FMOs but not in mammalian FMO 1, FMO 2, frog FMOs, other fish FMOs and invertebrate FMOs. The sites under adaptive evolution were significantly associated with the insertion domain in mammalian FMO 5. We identified specific amino acid sites in FMOs 3–5 that are likely targets for selection based on the patterns of parallel amino acid change. The most likely role of adaptive evolution is the repair of mutations that permitted optimal NADP+ binding and improved catalytic efficiency. The occurrence of positive selection during the evolution of phase I detoxification enzymes such as FMOs 3–5 and fugu FMO suggests the occurrence of both high selection pressure acting on species within their unique habitats and significant changes in intensity and direction (forms of xenobiotics and drugs) resulting from changes in microhabitat and food.     

Comparative genomic analysis reveals more functional nasal chemoreceptors in nocturnal mammals than in diurnal mammals

Natural selection has a critical role in the diversity of morphological traits. However, the genetic basis underlying the evolution and diversity of morphological characteristics, particularly in the context an organism’s behavior, lifestyle, and environment, is not well understood. The discovery of nasal chemoreceptors in mammals provided an opportunity to address this question. Here, we identify 4 nasal chemoreceptor gene families (V1R, V2R, OR, and TAAR) from horse, guinea pig, marmoset and orangutan genome sequences, respectively. Together with previously described mammalian nasal chemoreceptor gene repertoires, we found a significant positive correlation between functional gene number and morphological complexity, both in the main olfactory system and the vomeronasal system. The combined analysis of morphological data, behavioral data, and gene repertoires suggests that nocturnal mammals tend to possess more species-specific chemoreceptor genes and more complicated olfactory organs than diurnal mammals. Moreover, analysis of evolutionary forces revealed the existence of positive selection on the species-specific genes, likely reflecting the species-specific detection of odors and pheromones. Taken together, these results reflect a rare case of adaptation to circadian rhythm activity at the genome scale, and strongly suggest that the complexity of morphological olfactory organs and the diversification of nasal chemoreceptors in nocturnal mammals are under selection for the ability to perceive the variety of odors that nocturnal mammals may encounter in their particular dark environments.     

Molecular evolution of stress-response gene Leptin in high-altitude Chinese snub-nosed monkeys (Rhinopithecus genus)

Chinese snub-nosed monkeys (genus Rhinopithecus, subfamily Colobinae), including R. bieti, R. brelichi and R. roxellana, are well-known as the non-human primates with the highest known altitudinal distribution. They represent an interesting model organism of adaptation to the extreme environmental stresses. However, no study at the molecular level has yet been reported for the high-altitude adaptation in Chinese snub-nosed monkeys. Leptin, as an adipocyte-derived hormone, is believed to play an important role in energy homeostasis in adaptation to high altitude environments. In the present study, we sequenced and compared leptin sequences of the Chinese snub-nosed monkeys (R. bieti and R. roxellana) with their lowland close relative R. avunculus and other Colobines. Unexpectedly, no amino acid changes were observed in the 7 Colobinae species examined, including the 2 Chinese snub-nosed monkeys, indicating no difference in the evolutionary pattern of the Leptin gene between high-altitude monkeys and their lowland counterparts. In contrast to a previous finding of adaptive evolution of Leptin gene in plateau pikas, our study suggests that this gene may not have an important role in high-altitude adaptation of Chinese snub-nosed monkeys. Other nuclear genes associated with energy metabolism, or mitochondrial genes, are most likely to be involved the molecular mechanism underlying adaptation of these monkeys to cold and hypoxia associated with the highland environment.     

Positive Darwinian selection in human population: A review

This paper reviews a large number of genes under positive Darwinian selection in modern human populations, such as brain development genes, immunity genes, reproductive related genes, percep- tion receptors. The research on the evolutionary property of these genes will provide important insight into human evolution and disease mechanisms. With the increase of population genetics and com- parative genomics data, more and more evidences indicate that positive Darwinian selection plays an indispensable role in the origin and evolution of human beings. This paper will also summarize the methods to detect positive selection, analyze the interference factors faced and make suggestions for further research on positive selection.     

Scanning for sisnatures of geosraphically restricted selection based on population genomics analysis

Natural selection, as the driving force of human evolution, has direct impact on population differentiation. However, it is still unclear to what extent the genetic differentiation has been caused by natural selection. To explore this question, we performed a genome-wide scan with single nucleotide polymorphism （SNP） data from the International HapMap Project. Single locus FsTanalysis was applied to assess the frequency difference among populations in autosomes. Based on the empirical distribution of FsT, we identified 12669 SNPs correlating to population differentiation and 1853 candidate genes subjected to geographic restricted natural selection. Further interpretation of gene ontogeny revealed 121 categories of biological process with the enrichments of candidate genes. Our results suggest that natural selection may play an important role in human population differentiation. In addition, our analysis provides new clues as well as research methods for our understanding of population differentiation and natural selection.     

GFPT2基因系统发育与功能生物信息学分析

GFPT2作为己糖胺代谢重要的转录因子,在动物的多种疾病发生发展中起着重要作用。利用生物信息学方法对GFPT2蛋白的组分、功能、正选择位点及其分子进化进行了详细的分析。结果表明:13条不同物种氨基酸序列组分分析显示亮氨酸占比最高为9.86%,含量最低的氨基酸为色氨酸(0.15%),平均长度为664.8。系统进化树和结构域显示人和猴子的亲缘性最近,其次是大鼠、小鼠,所有氨基酸均包含两个SIS保守结构域。混合效应-演化模型(mixed effects model of evolution, MEME)和固定效应(fixed effects likelihood, REL)方法共发现8个正选择位点。基因本体论(gene ontology, GO)功能富集分析发现GFPT2主要参与GFPT酶活性、蛋白结合、碳水化合物衍生物结合方面发挥作用等生物学过程。京都基因与基因组百科全书(Kyoto encyclopedia of gene and genomes, KEGG)分析显示差异基因主要参与氨基糖和核苷酸糖代谢,丙氨酸、天冬氨酸和谷氨酸代谢,胰岛素抵抗3条信号通路。并且筛选到与GFPT2相互作用的10个基因:GFPT1、GLUL、GNPDA1、GNPNAT1、GPI、HK1、MPI、PPAT、AMDHD2、CAD。研究结果可以为GFPT2分子功能的深层次研究提供一定的借鉴作用,对进一步探究由己糖胺代谢导致的代谢异常及心血管疾病治疗具有重要的现实意义。     

Parallel adaptive radiations in two major clades of placental mammals

Higher level relationships among placental mammals, as well as the historical biogeography and morphological diversification of this group, remain unclear. Here we analyse independent molecular data sets, having aligned lengths of DNA of 5,708 and 2,947 base pairs, respectively, for all orders of placental mammals. Phylogenetic analyses resolve placental orders into four groups: Xenarthra, Afrotheria, Laurasiatheria, and Euarchonta plus Glires. The first three groups are consistently monophyletic with different methods of analysis. Euarchonta plus Glires is monophyletic or paraphyletic depending on the phylogenetic method. A unique nine-base-pair deletion in exon 11 of the BRCA1 gene provides additional support for the monophyly of Afrotheria, which includes proboscideans, sirenians, hyracoids, tubulidentates, macroscelideans, chrysochlorids and tenrecids. Laurasiatheria contains cetartiodactyls, perissodactyls, carnivores, pangolins, bats and eulipotyphlan insectivores. Parallel adaptive radiations have occurred within Laurasiatheria and Afrotheria. In each group, there are aquatic, ungulate and insectivore-like forms.     

Detecting positive darwinian selection in brain-expressed genes during human evolution

To understand the genetic basis that underlies the phenotypic divergence between human and non- human primates, we screened a total of 7176 protein-coding genes expressed in the human brain and compared them with the chimpanzee orthologs to identify genes that show evidence of rapid evolution in the human lineage. Our results showed that the nonsynonymous/synonymous substitution (Ka/Ks) ratio for genes expressed in the brain of human and chimpanzee is 0.3854, suggesting that the brain-expressed genes are under functional constraint. The X-linked human brain-expressed genes evolved more rapidly than autosomal ones. We further dissected the molecular evolutionary patterns of 34 candidate genes by sequencing representative primate species to identify lineage-specific adaptive evolution. Fifteen out of the 34 candidate genes showed evidence of positive Darwinian selection in human and/or chimpanzee lineages. These genes are predicted to play diverse functional roles in em- bryonic development, spermatogenesis and male fertility, signal transduction, sensory nociception, and neural function. This study together with others demonstrated the usefulness and power of phy- logenetic comparison of multiple closely related species in detecting lineage-specific adaptive evolu- tion, and the identification of the positively selected brain-expressed genes may add new knowledge to the understanding of molecular mechanism of human origin.     

Using maximum likelihood method to detect adaptive evolution of HCV envelope protein-coding genes

The basic process of adaptive evolution by natural selection is the replacement of one allele gene by an- other with a higher fitness in a population. Detecting the adaptive evolution would be helpful for better un- derstanding of bio-evolutionary mechani…     

Episodic evolution of prolactin gene in primates

In the present study, we obtained exon 2--5 of prolactin (PRL) gene from four primate species by PCR and sequencing. Adding other genes available in GenBank, we calculate amino acid substitution rates for prolactin gene in primate. Comparison of nonsynonymous substitution rate to synonymous substitution rate ratios shows no evidence of positive selection for any lineage of primate prolactin gene.According to this and the facts that (i) no sites under positive selection are inferred by using maximum-likelihood method;(ii) among 32 amino acid replacement that occurred along the rapid evolutionary phase, only two are included in the 40 functionally important residues, indicating that amino acid replacement tends to occur in those functionally unimportant residues; (iii) partial of prolactin function is replaced by placental lactogen in primate at the rapid evolutionary phase of prolactin gene, we thus deem that it is relaxation of purifying selection to some extent rather than positive selection that enforces the rapid evolution of primate prolactin gene.     

禾本科植物β-淀粉酶基因家族分子进化及响应非生物胁迫的表达模式分析

 β-淀粉酶(beta-amylase,BAM)是一类关键的淀粉水解酶,在禾谷类作物生长发育过程中起着重要作用,与植物多种非生物胁迫响应相关.本研究通过系统发育分析,将水稻、玉米、高粱、谷子、二穗短柄草5 种禾本科植物中共54 个BAM 基因分为10 个同源基因簇,每个同源基因簇都涵盖了这5 个物种,因此推测在禾本科祖先物种中至少含有10 个BAM 基因,并且在禾本科植物分化后没有发生明显的基因丢失事件.基于对编码蛋白质序列的功能分化分析,表明同源基因簇间存在明显的进化速率的差异.对10 个同源基因簇进行了适应性进化检测,发现有3 个同源簇在禾本科植物的进化过程中经历了适应性进化.此外,对水稻β-淀粉酶的表达分析发现,一些β-淀粉酶具有组织特异性表达特征,并且至少有5 个水稻的β-淀粉酶基因具有受到非生物逆境的胁迫而表现出不同的表达模式.本研究结果为进一步探讨禾本科BAM 基因的生物学功能提供了一定的理论基础.     

Sequence analysis of the Microcystis aeruginosa FACHB-912 phytochrome gene supports positive selection in cyanobacteria

The phytochrome gene from Microcystis aeruginosa FACHB-912,isolated from algal blooms in Taihu Lake in China,was sequenced and found to code for a wavelength transition light receptor protein.The gene was composed of five distinct domains:a PAS fold domain,a GAF domain,a phytochrome domain,a His Kinase A(phosphoacceptor) domain,and a histidine kinase domain.Red-absorbing phytochrome,far-red-absorbing phytochrome,and photoconversion kinetics were monitored via the spectral characteristics of the protein.To detect positive selection,homologous sequences from cyanobacterium phytochrome genes were obtained from GenBank.Potential selective pressure was identified by phylogenetic analysis with maximum likelihood analyses.The frequency of the phytochrome gene being subjected to selective constraints suggests that positive selection is a potentially important mechanism that promotes the evolution of the cyanobacteria phytochrome gene.The sites identified in this study provide targets for further research on the structural-functional role of these residues,and on the correlation with the mechanism of algal blooms.     

Phylogenetic origins and adaptive evolution of avian and mammalian haemoglobin genes

Recent years have seen rapid growth in amino acid sequence data on globins and nucleotide sequence data on haemoglobin genes and pseudogenes, and cladistic analysis of these data continues to reveal new facets of globin evolution. Our present findings demonstrate: (1) avian and mammalian embryonic alpha genes (pi and xi, respectively) had a monophyletic origin involving an alpha locus duplication about 400 Myr ago soon after the duplication which separated alpha and beta genes; (2) much later in phylogeny, independent beta-gene duplications produced the embryonic rho locus of birds and embryonic epsilon and fetal gamma loci of mammals. This parallels the earlier finding that myoglobins evolved more than once from generalized globin ancestors. Here we support the view that such globin evolution resulted from natural selection acting on mutations in duplicated genes. Thus, our evidence contradicts the neutralist view in which almost all amino acid substitutions in descent to extant globins evaded positive selection.     

Vertical adaptive radiation in ocean Prochlorococcus: Evolutionary implications of the Chl b/a ratio from molecular evidence

Prochlorococcus is a marine cyanobacterium of global significance. Two ecotypes are adapted to either high-light (HL) or low-light (LL) conditions. The ratio between chlorophyll (Chl) a and b is a distinguishing characteristic of these two ecotypes. However, how this ratio evolved in Prochlorococcus during this ecotype differentiation remains unclear. Our analyses reveal that the ancestor of Prochlorococcus was typically low-light adapted. The LL ecotype showed a stagnant evolution, and the HL ecotype was recently diverged. There was an adaptive radiation after directional evolution in the Chl b/a ratio regulation. Recombination in chlorophyllide a oxygenase (CAO) and positive selection on Clp protease contributed to the directional evolution of Prochlorococcus. The recombinant fragments of CAO were correlated with a large group of shared coevolving sites. Evidence of positive selection was found in both subunits of Clp. Chl b/a ratio evolution, as annotated by molecular evidence, appears to be among the crucial reasons that explain how Prochlorococcus has become the dominant photosynthetic organism in the ocean.     

Adaptive evolution of non-coding DNA in Drosophila

A large fraction of eukaryotic genomes consists of DNA that is not translated into protein sequence, and little is known about its functional significance. Here I show that several classes of non-coding DNA in Drosophila are evolving considerably slower than synonymous sites, and yet show an excess of between-species divergence relative to polymorphism when compared with synonymous sites. The former is a hallmark of selective constraint, but the latter is a signature of adaptive evolution, resembling general patterns of protein evolution in Drosophila. I estimate that about 40-70% of nucleotides in intergenic regions, untranslated portions of mature mRNAs (UTRs) and most intronic DNA are evolutionarily constrained relative to synonymous sites. However, I also use an extension to the McDonald-Kreitman test to show that a substantial fraction of the nucleotide divergence in these regions was driven to fixation by positive selection (about 20% for most intronic and intergenic DNA, and 60% for UTRs). On the basis of these observations, I suggest that a large fraction of the non-translated genome is functionally important and subject to both purifying selection and adaptive evolution. These results imply that, although positive selection is clearly an important facet of protein evolution, adaptive changes to non-coding DNA might have been considerably more common in the evolution of D. melanogaster.     

Origin and evolution of new exons in the rodent zinc finger protein 39 gene

The origin of new structures and functions is an important process in evolution. In the past decades, we have obtained some preliminary knowledge of the origin and evolution of new genes. However, as the basic unit of genes, the origin and evolution of exons remain unclear. Because young exons retain the footprints of origination, they can be good materials for studying origin and evolution of new exons. In this paper, we report two young exons in a zinc finger protein gene of rodents. Since they are unique sequences in mouse and rat genome and no homologous sequences were found in the orthologous genes of human and pig, the young exons might originate after the divergence of primates and rodents through exonization of intronic sequences. Strong positive selection was detected in the new exons between mouse and rat, suggesting that these exons have undergone significant functional divergence after the separation of the two species. On the other hand, population genetics data of mouse demonstrate that the new exons have been subject to functional constraint, indicating an important function of the new exons in mouse. Functional analyses suggest that these new exons encode a nuclear localization signal peptide, which may mediate new ways of nuclear protein transport. To our knowledge, this is the first example of the origin and evolution of young exons.     

Cloning the interferon regulatory factor I gene in lungfish （Protopterus annectens） and its molecular evolution among sarcopterygians

Sarcopterygians is an important vertebrate clade that includes crossopterygians and tetrapods. Crossopterygians are lobe-finned fish that include lungfish and coelacanths. Tetrapods include amphibians, reptiles, avians and mammals. To compare the interferon regulatory factor 1 (irf-1) gene structure and to explore phylogenetic relationships among sarcopterygians, we cloned the cDNA sequence of irf-1 from lungfish and compared it with irf-1 orthologs in other sarcopterygian species. The lungfish is a primitive sarcopterygian that occupies a very important position in vertebrate phylogeny. Interferon regulatory factors (IRFs) are a family of proteins involved in innate immunity. To date, 11 IRF family members have been reported. All IRFs share homology in the first 115 amino acids, which encompasses a DNA binding domain containing a characteristic repeat of 5 tryptophan residues separated by 10–18 amino acids. IRF-1 and IRF-2 were the first members of this family to be reported and they have a very important role in innate immunity. However, studies of the irf-1 and irf-2 genes are mostly confined to mammals; very few non-mammalian irf-1 genes have been reported. Consistent with the irf-1 gene sequences already published, the first 345 nucleotides of lungfish irf-1 are highly conserved. At the carboxyl terminal a C-terminal transactivating region motif and an interferon associated domain (IAD2) were identified. 417 million years separate the present from the closest common ancestor of lungfish and tetrapods; however, the irf-1 genes among sarcopterygians are highly conserved and have very obvious phylogenetic relationships. Also the interrelationship tree of sarcopterygians, based on IRF-1 amino acid sequences, is identical with trees produced using other data, such as morphological characteristics or mitochondrial gene sequences.