Polymorphism and gene organization of water buffalo MHC-DQB genes show homology to the BoLA DQB region

In cattle (Bos taurus), there is evidence of more than 50 alleles of BoLA-DQB (bovine lymphocyte antigen DQB) that are distributed across at least five DQB loci, making this region one of the most complex in the BoLA gene family. In this study, DQB alleles were analysed for the water buffalo (Bubalus bubalis), another economically important bovine species. Twelve alleles for Bubu-DQB (Bubalis bubalis DQB) were determined by nucleotide sequence analysis. A phylogenetic analysis revealed numerous trans-species polymorphisms, with alleles from water buffalo assigned to at least three different loci (BoLA-DQB1, BoLA-DQB3 and BoLA-DQB4) that are also found in cattle. These presumptive loci were analysed for patterns of synonymous (d(S)) and non-synonymous (d(N)) substitution. Like BoLA-DQB1, Bubu-DQB1 was observed to be under strong positive selection for polymorphism. We conclude that water buffalo and cattle share the current arrangement of their DQB region because of their common ancestry.     

Genetic signatures of strong recent positive selection at the lactase gene

In most human populations, the ability to digest lactose contained in milk usually disappears in childhood, but in European-derived populations, lactase activity frequently persists into adulthood (Scrimshaw and Murray 1988). It has been suggested (Cavalli-Sforza 1973; Hollox et al. 2001; Enattah et al. 2002; Poulter et al. 2003) that a selective advantage based on additional nutrition from dairy explains these genetically determined population differences (Simoons 1970; Kretchmer 1971; Scrimshaw and Murray 1988; Enattah et al. 2002), but formal population-genetics-based evidence of selection has not yet been provided. To assess the population-genetics evidence for selection, we typed 101 single-nucleotide polymorphisms covering 3.2 Mb around the lactase gene. In northern European-derived populations, two alleles that are tightly associated with lactase persistence (Enattah et al. 2002) uniquely mark a common (~77%) haplotype that extends largely undisrupted for >1 Mb. We provide two new lines of genetic evidence that this long, common haplotype arose rapidly due to recent selection: (1) by use of the traditional F(ST) measure and a novel test based on p(excess), we demonstrate large frequency differences among populations for the persistence-associated markers and for flanking markers throughout the haplotype, and (2) we show that the haplotype is unusually long, given its high frequency--a hallmark of recent selection. We estimate that strong selection occurred within the past 5,000-10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection we observe are among the strongest yet seen for any gene in the genome.     

Survival-variation within and between functional categories of the African multimammate rat

1. By identifying ecological factors specific to functional categories of individuals, it may be possible to understand the mechanisms underlying life-history evolution and population dynamics. While empirical analyses within the field of population biology have focused on changes in population size, theoretical models assuming differential sensitivities of population growth rate or fitness to demographic parameters have mostly been untested, particularly against data on small mammals.
2. Statistical modelling of capture–mark–recapture data on the multimammate rat ( Mastomys natalensis ) from Tanzania shows that: (i) females survive slightly better than males and subadults survive much better than adults; (ii) temporal variation of survival of all individuals is similarly related to the rainfall of the month; (iii) subadults exhibit a strongly density-dependent low persistence rate in the population immediately after their first capture; (iv) subadults survival in later months is, however, positively related to density; and (v) adult survival shows negative density-dependence.
3. Both density-dependent and density-independent factors simultaneously determine stage-dependent survival variation of the multimammate rat. Whereas environmental factors in this population seem to affect survival rates of all individuals in a similar manner, density-dependent relationships are more complex.
4. The patterns of survival variation in small mammals may be different from those observed in large mammals.
5. Further studies of demography in small mammals should aim at understanding how much of the variability in population growth rate is accounted for by the variability of the demographic rates resulting from limiting (density-independent) and regulating (density-dependent) factors, respectively. This study emphasizes the use of robust and accurate statistical methods as well as stage- or age-structured population modelling.     

Complex signatures of selection and gene conversion in the duplicated globin genes of house mice

Results of electrophoretic surveys have suggested that hemoglobin polymorphism may be maintained by balancing selection in natural populations of house mice, Mus musculus. Here we report a survey of nucleotide variation in the adult globin genes of house mice from South America. We surveyed nucleotide polymorphism in two closely linked alpha-globin paralogs and two closely linked beta-globin paralogs to test whether patterns of variation are consistent with a model of long-term balancing selection. Surprisingly high levels of nucleotide polymorphism at the two beta-globin paralogs were attributable to the segregation of two highly divergent haplotypes, Hbbs (which carries two identical beta-globin paralogs) and Hbbd (which carries two functionally divergent beta-globin paralogs). Interparalog gene conversion on the Hbbs haplotype has produced a highly unusual situation in which the two paralogs are more similar to one another than either one is to its allelic counterpart on the Hbbd haplotype. Levels of nucleotide polymorphism and linkage disequilibrium at the two beta-globin paralogs suggest a complex history of diversity-enhancing selection that may be responsible for long-term maintenance of alternative protein alleles. The alternative two-locus beta-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function.     

Positive selection signatures in the TLR7 family

While adaptive immunity genes evolve rapidly under the influence of positive selection, innate immune system genes are known to evolve slowly due to strong purifying selection. Among the sensors of the innate immune system, Toll-like receptors (TLRs) are particularly important due to their ability to recognize and respond to pathogen-associated molecular patterns (PAMP), such as lipopolysaccharides, peptidoglycans, and nucleic acids from bacteria or viruses. In the present study, we examine the evolutionary process that has operated on the TLR7 family genes TLR7, TLR8, and TLR9. The results demonstrate that the average Ka/Ks (the ratio between nonsynonymous and synonymous substitution rates) of each TLR family gene is far lower than one regardless of estimating methods, supporting previous observations of strong purifying selection in this gene family. Interestingly, however, analysis of Ka/Ks ratios along the coding regions of TLR7 family genes by sliding-window analysis reveals a few narrow high peaks (Ka/Ks > 1). The most prominent peak corresponds to a specific region in the ectodomain, which exists only in the TLR7 family, suggesting that this unique structure of the TLR7 family might have been a target of positive selection in a variety of lineages. Furthermore, maximum likelihood model tests suggest that positive selection is the best explanation for a certain fraction of the amino acid substitutions in the TLR9.     

用PCR-RFLP方法研究藏族HLA-DQA1和-DQB1基因多态性

应用目前HLA研究领域中成熟的,有效的PCR-RFLP基因分型技术,从DNA水平对藏族健康群体进行了HLA-DQA1(49人)和-DQB1(49人)基因分型,这在国内外属首次。所采用的PCR-RFLP基因分型技术是在HLA-DQA1和-DQB1各等位基因全部序列已知的情况下,对其第2个外显子碱基序列扩增进而进行RFLP分析的方法。这种方法得到的RFLP的所有片段都是已知序列,因而精确度很高,同时为发现新的等位基因提供了成熟而有效的分析方法。研究结果表明,在藏族DQA1的8个等位基因,DQA1*0301的基因频率最高(36.74％)。DQA1*0601(4.08％)、*0103(4.08％)和*0401(5.10％)最低。在DQB1的16个等位基因中,OQB1*0302(16.33％)、*0303(15.31％)和*0602(15.31％)为最常见,没有观察到*0504。统计分析表明,在DQA1各等位基因分布上,藏族与新疆汉族、北方汉族、上海汉族十分相近;与维吾尔族和哈萨克族也没有明显差异。在OQB1各等位基因的分布上,藏族与汉族、维族、哈族之间略有差异,而汉族、维族、哈族之间也存在一些差异。     

Identification of selection signatures in livestock species

The identification of regions that have undergone selection is one of the principal goals of theoretical and applied evolutionary genetics. Such studies can also provide information about the evolutionary processes involved in shaping genomes, as well as physical and functional information about genes/genomic regions. Domestication followed by breed formation and selection schemes has allowed the formation of very diverse livestock breeds adapted to a wide variety of environments and with special characteristics. The advances in genomics in the last five years have enabled the development of several methods to detect selection signatures and have resulted in the publication of a considerable number of studies involving livestock species. The aims of this review are to describe the principal effects of natural/artificial selection on livestock genomes, to present the main methods used to detect selection signatures and to discuss some recent results in this area. This review should be useful also to research scientists working with wild animals/non-domesticated species and plant biologists working with breeding and evolutionary biology.     

Polymorphism with migration and selection

Summary Two single-locus, deterministic models with discrete nonoverlapping generations are formulated for the maintenance of genetic variation in each of two distinct biological situations. The first two models are applicable to an autosomal locus in an hermaphroditic plant population with mixed selfing and random mating. They describe the interaction of migration and viability selection for, respectively, an island migration model and for a subdivided population. Pollen as well as seed may disperse. Sufficient conditions are derived and discussed for the existence of protected polymorphism in the diallelic case. The remaining two models are pertinent to migration and selection at a single X-linked locus. An island model is again considered as well as that of a subdivided population. Mating is at random, selection occurs only through viability differences, and the migration structure for males and females may differ. For a diallelic population, protection conditions are derived and discussed vis-à-vis the autosomal case.M.M. was supported by a U.S. Public Health Service training grant (Grant No. GM780).     

Identifying signatures of sexual selection using genomewide selection components analysis

Sexual selection must affect the genome for it to have an evolutionary impact, yet signatures of selection remain elusive. Here we use an individual‐based model to investigate the utility of genome‐wide selection components analysis, which compares allele frequencies of individuals at different life history stages within a single population to detect selection without requiring a priori knowledge of traits under selection. We modeled a diploid, sexually reproducing population and introduced strong mate choice on a quantitative trait to simulate sexual selection. Genome‐wide allele frequencies in adults and offspring were compared using weighted F_ST values. The average number of outlier peaks (i.e., those with significantly large F_ST values) with a quantitative trait locus in close proximity (“real” peaks) represented correct diagnoses of loci under selection, whereas peaks above the F_ST significance threshold without a quantitative trait locus reflected spurious peaks. We found that, even with moderate sample sizes, signatures of strong sexual selection were detectable, but larger sample sizes improved detection rates. The model was better able to detect selection with more neutral markers, and when quantitative trait loci and neutral markers were distributed across multiple chromosomes. Although environmental variation decreased detection rates, the identification of real peaks nevertheless remained feasible. We also found that detection rates can be improved by sampling multiple populations experiencing similar selection regimes. In short, genome‐wide selection components analysis is a challenging but feasible approach for the identification of regions of the genome under selection.     

Genetic distinction between contiguous urban and rural multimammate mice in Tanzania despite gene flow

Special conditions are required for genetic differentiation to arise at a local geographical scale in the face of gene flow. The Natal multimammate mouse, Mastomys natalensis, is the most widely distributed and abundant rodent in sub‐Saharan Africa. A notorious agricultural pest and a natural host for many zoonotic diseases, it can live in close proximity to humans and appears to compete with other rodents for the synanthropic niche. We surveyed its population genetic structure across a 180‐km transect in central Tanzania along which the landscape varied between agricultural land in a rural setting and natural woody vegetation, rivers, roads and a city (Morogoro). We sampled M. natalensis across 10 localities and genotyped 15 microsatellite loci from 515 individuals. Hierarchical STRUCTURE analyses show a K‐invariant pattern distinguishing Morogoro suburbs (located in the centre of the transect) from nine surrounding rural localities. Landscape connectivity analyses in Circuitscape and comparison of rainfall patterns suggest that neither geographical isolation nor natural breeding asynchrony could explain the genetic differentiation of the urban population. Using the isolation‐with‐migration model implemented in IMa2, we inferred that a split between suburban and rural populations would have occurred recently (<150 years ago) with higher urban effective population density consistent with an urban source to rural sink of effective migration. The observed genetic differentiation of urban multimammate mice is striking given the uninterrupted distribution of the animal throughout the landscape and the high estimates of effective migration (2N_eM = 3.0 and 29.7), suggesting a strong selection gradient across the urban boundary.     

Polymorphism and differential selection for the sexes.

Various genetic models with different fitnesses for the sexes are investigated. Only a limited set of fitness values will result in a stable polymorphism, and the rate of approach to these equilibrium frequencies is extremely slow. These results indicate that there are problems associated with the interpretation of some human genetic traits by such models.     

Polymorphism with selection and genotype-dependent migration

For a single autosomal locus with multiple alleles both an island and a multiple-niche model with discrete nonoverlapping generations are formulated for the maintenance of genetic variability. Both models incorporate viability selection in an arbitrary way and allow for genotypic differences in the pertinent migration structure. Random drift is ignored, and mating is at random. A global analysis is given for the island model in the neutral case. For a subdivided population, conditions are derived for the existence of a protected polymorphism, and the model is examined in some special two-niche cases. Of particular consideration is the loss of neutral alleles due solely to population regulation and genotype-dependent migration, and the possible existence of equilibrium clines without selection.M. M. was supported by USPHS Pre-doctoral training grant No. GM 7197 to the University of Chicago; this work represents part of the author's Doctoral dissertation.     

Detecting selection signatures in three Iranian sheep breeds

The objective of genome mapping is to achieve valuable insight into the connection between gene variants (genotype) and observed traits (phenotype). Part of that objective is to understand the selective forces that have operated on a population. Finding links between genotype–phenotype changes makes it possible to identify selective sweeps by patterns of genetic variation and linkage disequilibrium. Based on Illumina 50KSNP chip data, two approaches, XP‐EHH (cross‐population extend haplotype homozygosity) and F_ST (fixation index), were carried out in this research to identify selective sweeps in the genome of three Iranian local sheep breeds: Baluchi (n = 86), Lori‐Bakhtiari (n = 45) and Zel (n = 45). Using both methods, 93 candidate genomic regions were identified as harboring putative selective sweeps. Bioinformatics analysis of the genomic regions showed that signatures of selection related to multiple candidate genes, such as HOXB9, HOXB13, ACAN, NPR2, TRIL, AOX1, CSF2, GHR, TNS2, SPAG8, HINT2, ALS2, AAAS, RARG, SYCP2, CAV1, PPP1R3D, PLA2G7, TTLL7 and C20orf10, that play a role in skeletal system and tail, sugar and energy metabolisms, growth, reproduction, immune and nervous system traits. Our findings indicated diverse genomic selection during the domestication of Iranian sheep breeds.