共查询到20条相似文献,搜索用时 46 毫秒
1.
Despite the widespread study of genetic variation in admixed human populations, such as African-Americans, there has not been an evaluation of the effects of recent admixture on patterns of polymorphism or inferences about population demography. These issues are particularly relevant because estimates of the timing and magnitude of population growth in Africa have differed among previous studies, some of which examined African-American individuals. Here we use simulations and single-nucleotide polymorphism (SNP) data collected through direct resequencing and genotyping to investigate these issues. We find that when estimating the current population size and magnitude of recent growth in an ancestral population using the site frequency spectrum (SFS), it is possible to obtain reasonably accurate estimates of the parameters when using samples drawn from the admixed population under certain conditions. We also show that methods for demographic inference that use haplotype patterns are more sensitive to recent admixture than are methods based on the SFS. The analysis of human genetic variation data from the Yoruba people of Ibadan, Nigeria and African-Americans supports the predictions from the simulations. Our results have important implications for the evaluation of previous population genetic studies that have considered African-American individuals as a proxy for individuals from West Africa as well as for future population genetic studies of additional admixed populations.STUDIES of archeological and genetic data show that anatomically modern humans originated in Africa and more recently left Africa to populate the rest of the world (Tishkoff and Williams 2002; Barbujani and Goldstein 2004; Garrigan and Hammer 2006; Reed and Tishkoff 2006; Campbell and Tishkoff 2008; Jakobsson et al. 2008; Li et al. 2008). Given the central role Africa has played in the origin of diverse human populations, understanding patterns of genetic variation and the demographic history of populations within Africa is important for understanding the demographic history of global human populations. The availability of large-scale single-nucleotide polymorphism (SNP) data sets coupled with recent advances in statistical methodology for inferring parameters in population genetic models provides a powerful means of accomplishing these goals (Keinan et al. 2007; Boyko et al. 2008; Lohmueller et al. 2009; Nielsen et al. 2009).It is important to realize that studies of African demographic history using genetic data have come to qualitatively different conclusions regarding important parameters. Some recent studies have found evidence for ancient (>100,000 years ago) two- to fourfold growth in African populations (Adams and Hudson 2004; Marth et al. 2004; Keinan et al. 2007; Boyko et al. 2008). Other studies have found evidence of very recent growth (Pluzhnikov et al. 2002; Akey et al. 2004; Voight et al. 2005; Cox et al. 2009; Wall et al. 2009) or could not reject a model with a constant population size (Pluzhnikov et al. 2002; Voight et al. 2005). It is unclear why studies found such different parameter estimates. However, these studies all differ from each other in the amount of data considered, the types of data used (e.g., SNP genotypes vs. full resequencing), the genomic regions studied (e.g., noncoding vs. coding SNPs), and the types of demographic models considered (e.g., including migration vs. not including migration postseparation of African and non-African populations).Another important way in which studies of African demographic history differ from each other is in the populations sampled. Some studies have focused on genetic data from individuals sampled from within Africa (Pluzhnikov et al. 2002; Adams and Hudson 2004; Voight et al. 2005; Keinan et al. 2007; Cox et al. 2009; Wall et al. 2009), while other studies included American individuals with African ancestry (Adams and Hudson 2004; Akey et al. 2004; Marth et al. 2004; Boyko et al. 2008). While there is no clear correspondence between those studies which sampled native African individuals (as opposed to African-Americans) and particular growth scenarios, it is clear from previous studies that African-American populations do differ from African populations in their recent demographic history. In particular, genetic studies suggest that there is wide variation in the degree of European admixture in most African-American individuals in the United States and that they have, on average, ∼80% African ancestry and 20% European ancestry (Parra et al. 1998; Pfaff et al. 2001; Falush et al. 2003; Patterson et al. 2004; Tian et al. 2006; Lind et al. 2007; Reiner et al. 2007; Price et al. 2009; Bryc et al. 2010). Furthermore, both historical records and genetic evidence suggest that the admixture process began quite recently, within the last 20 generations (Pfaff et al. 2001; Patterson et al. 2004; Seldin et al. 2004; Tian et al. 2006). Recent population admixture can alter patterns of genetic variation in a discernible and predictable way. For example, recently admixed populations will exhibit correlation in allele frequencies (i.e., linkage disequilibrium) among markers that differ in frequency between the parental populations. This so-called admixture linkage disequilibrium (LD) (Chakraborty and Weiss 1988) can extend over long physical distances (Lautenberger et al. 2000) and decays exponentially with time the since the admixture process began (i.e., recently admixed populations typically exhibit LD over a longer physical distance than anciently admixed populations).While it is clear that African-American populations have a different recent demographic history than do African populations from within Africa and that admixture tracts can be identified in admixed individuals (Falush et al. 2003; Patterson et al. 2004; Tang et al. 2006; Sankararaman et al. 2008a,b; Price et al. 2009; Bryc et al. 2010), the effect that admixture has on other patterns of genetic variation remains unclear. For example, Xu et al. (2007) found similar LD decay patterns when comparing African-American and African populations. It is also unclear whether the recent admixture affects our ability to reconstruct ancient demographic events (such as expansions that predate the spread of humans out of Africa) from whole-genome SNP data. Most studies of demographic history have summarized the genome-wide SNP data by allele frequency or haplotype summary statistics. If these summary statistics are not sensitive to the recent European admixture, then the African-American samples may yield estimates of demographic parameters that are close to the true demographic parameters for the ancestral, unsampled, African populations. This would suggest that the differences in growth parameter estimates obtained from African populations cannot be explained by certain studies sampling African-American individuals and others sampling African individuals from within Africa. However, if these statistics are sensitive to recent admixture, then they may give biased estimates of growth parameters.Here, we examine the effect of recent admixture on the estimation of population demography. In particular, we estimate growth parameters from simulated data sets using SNP frequencies as well as a recently developed haplotype summary statistic (Lohmueller et al. 2009). We compare the demographic parameter estimates made from the admixed and nonadmixed populations and find that some parameter estimates are qualitatively similar between the two populations when inferred using allele frequencies. Inferences of growth using haplotype-based approaches appear to be more sensitive to recent admixture than inferences based on SNP frequencies. We discuss implications that our results have for interpreting studies of demography in admixed populations. 相似文献
2.
Roman Yukilevich Thomas L. Turner Fumio Aoki Sergey V. Nuzhdin John R. True 《Genetics》2010,186(1):219-239
Genomic tools and analyses are now being widely used to understand genome-wide patterns and processes associated with speciation and adaptation. In this article, we apply a genomics approach to the model organism Drosophila melanogaster. This species originated in Africa and subsequently spread and adapted to temperate environments of Eurasia and the New World, leading some populations to evolve reproductive isolation, especially between cosmopolitan and Zimbabwean populations. We used tiling arrays to identify highly differentiated regions within and between North America (the United States and Caribbean) and Africa (Cameroon and Zimbabwe) across 63% of the D. melanogaster genome and then sequenced representative fragments to study their genetic divergence. Consistent with previous findings, our results showed that most differentiation was between populations living in Africa vs. outside of Africa (i.e., “out-of-Africa” divergence), with all other geographic differences being less substantial (e.g., between cosmopolitan and Zimbabwean races). The X chromosome was much more strongly differentiated than the autosomes between North American and African populations (i.e., greater X divergence). Overall differentiation was positively associated with recombination rates across chromosomes, with a sharp reduction in regions near centromeres. Fragments surrounding these high FST sites showed reduced haplotype diversity and increased frequency of rare and derived alleles in North American populations compared to African populations. Nevertheless, despite sharp deviation from neutrality in North American strains, a small set of bottleneck/expansion demographic models was consistent with patterns of variation at the majority of our high FST fragments. Although North American populations were more genetically variable compared to Europe, our simulation results were generally consistent with those previously based on European samples. These findings support the hypothesis that most differentiation between North America and Africa was likely driven by the sorting of African standing genetic variation into the New World via Europe. Finally, a few exceptional loci were identified, highlighting the need to use an appropriate demographic null model to identify possible cases of selective sweeps in species with complex demographic histories.THE study of genetic differentiation between populations and species has recently been empowered by the use of genomic techniques and analysis (e.g., Noor and Feder 2006; Stinchcombe and Hoekstra 2008). In the past decade, genetic studies of adaptation and speciation have taken advantage of emerging molecular techniques to scan the genomes of diverging populations for highly differentiated genetic regions (e.g., Wilding et al. 2001; Emelianov et al. 2003; Beaumont and Balding 2004; Campbell and Bernatchez 2004; Scotti-Saintagne et al. 2004; Achere et al. 2005; Turner et al. 2005; Vasemagi et al. 2005; Bonin et al. 2006, 2007; Murray and Hare 2006; Savolainen et al. 2006; Yatabe et al. 2007; Nosil et al. 2008, 2009; Turner et al. 2008a,b; Kulathinal et al. 2009). As a result, genome scans can identify candidate regions that may be associated with adaptive evolution between diverging populations and, more broadly, are able to describe genome-wide patterns and processes of population differentiation (Begun et al. 2007; Stinchcombe and Hoekstra 2008).Genome scans in well-studied genetic model species such as Drosophila melanogaster gain particular power because differentiated loci are mapped to a well-annotated genome. Moreover, the evolutionary history of D. melanogaster is rich with adaptive and demographic events with many parallels to human evolution. Most notable is the historical out-of-Africa migration and subsequent adaptation to temperate ecological environments of Europe, Asia, North America, and Australia. This has resulted in widespread genetic and phenotypic divergence between African and non-African populations (e.g., David and Capy 1988; Begun and Aquadro 1993; Capy et al. 1994; Colegrave et al. 2000; Rouault et al. 2001; Takahashi et al. 2001; Caracristi and Schlötterer 2003; Baudry et al. 2004; Pool and Aquadro 2006; Schmidt et al. 2008; Yukilevich and True 2008a,b). Further, certain populations in Africa and in the Caribbean vary in their degree of reproductive isolation from populations in more temperate regions (Wu et al. 1995; Hollocher et al. 1997; Yukilevich and True 2008a,b). In particular, the Zimbabwe and nearby populations of southern Africa are strongly sexually isolated from all other populations, designating them as a distinct behavioral race (Wu et al. 1995).D. melanogaster has received a great deal of attention from the population geneticists in studying patterns of sequence variation across African and non-African populations. Many snapshots have been taken of random microsatellite and SNP variants spread across X and autosomes, and these have generated several important conclusions. Polymorphism patterns in European populations are characterized by reduced levels of nucleotide and haplotype diversity, an excess of high frequency-derived polymorphisms, and elevated levels of linkage disequilibrium relative to African populations (e.g., Begun and Aquadro 1993; Andolfatto 2001; Glinka et al. 2003; Haddrill et al. 2005; Ometto et al. 2005; Thornton and Andolfatto 2006; Hutter et al. 2007; Singh et al. 2007). These results have been generally interpreted as compatible with population size reduction/bottlenecks followed by recent population expansions. On the other hand, African populations are generally assumed either to have been relatively constant in size over time or to have experienced population size expansions. They generally show higher levels of nucleotide and haplotype diversity, an excess of rare variants, and a deficit of high frequency-derived alleles (Glinka et al. 2003; Ometto et al. 2005; Pool and Aquadro 2006; Hutter et al. 2007; but see Haddrill et al. 2005 for evidence of bottlenecks in Africa).Previous work also shows that the ratio of X-linked to autosomal polymorphism deviates from neutral expectations in opposite directions in African and European populations with more variation on the X than expected in Africa and less variation on the X than expected in Europe (Andolfatto 2001; Kauer et al. 2002; Hutter et al. 2007; Singh et al. 2007). The deviation from neutrality in the ratio of X-autosome polymorphism may be explained by positive selection being more prevalent on the X in Europe and/or by a combination of bottlenecks and male-biased sex ratios in Europe and female-biased sex ratios in Africa (Charlesworth 2001; Hutter et al. 2007; Singh et al. 2007). The selective explanation stems from the argument that, under the hitchhiking selection model, X-linked loci are likely to be more affected by selective sweeps than autosomal loci (Maynard Smith and Haigh 1974; Charlesworth et al. 1987; Vicoso and Charlesworth 2006, 2009).The relative contribution of selective and demographic processes in shaping patterns of genomic variation and differentiation is highly debated (Wall et al. 2002; Glinka et al. 2003; Haddrill et al. 2005; Ometto et al. 2005; Schöfl and Schlötterer 2004; Thornton and Andolfatto 2006; Hutter et al. 2007; Singh et al. 2007; Shapiro et al. 2007; Stephan and Li 2007; Hahn 2008; Macpherson et al. 2008; Noor and Bennett 2009; Sella et al. 2009). This is especially the case in D. melanogaster because derived non-African populations have likely experienced a complex set of demographic events during their migration out of Africa (e.g., Thornton and Andolfatto 2006; Singh et al. 2007; Stephan and Li 2007), making population genetics signatures of demography and selection difficult to tease apart (e.g., Macpherson et al. 2008). Thus it is still unclear what role selection has played in shaping overall patterns of genomic variation and differentiation relative to demographic processes in this species.While there is a long tradition in studying arbitrarily or opportunistically chosen sequences in D. melanogaster, genomic scans that focus particularly on highly differentiated sites across the genome have received much less attention. Such sites are arguably the best candidates to resolve the debate on which processes have shaped genomic differentiation within species (e.g., Przeworski 2002). Recently, a genome-wide scan of cosmopolitan populations in the United States and in Australia was performed to investigate clinal genomic differentiation on the two continents (Turner et al. 2008a). Many single feature polymorphisms differentiating Northern and Southern Hemisphere populations were identified. Among the most differentiated loci in common between continents, 80% were differentiated in the same orientation relative to the Equator, implicating selection as the likely explanation (Turner et al. 2008a). Larger regions of genomic differentiation within and between African and non-African populations have also been discovered, some of them possibly being driven by divergent selection (e.g., Dopman and Hartl 2007; Emerson et al. 2008; Turner et al. 2008a, Aguade 2009). Despite this recent progress, we still know relatively little about large-scale patterns of genomic differentiation in this species, especially between African and non-African populations, and whether most of this differentiation is consistent with demographic processes alone or if it requires selective explanations.In this work, we explicitly focus on identifying differentiated sites across the genome between U.S., Caribbean, West African, and Zimbabwean populations. This allows us to address several fundamental questions related to genomic evolution in D. melanogaster, such as the following: (1) Do genome-wide patterns of differentiation reflect patterns of reproductive isolation? (2) Is genomic differentiation random across and within chromosomes or are some regions overrepresented? (3) What are the population genetics properties of differentiated sites and their surrounding sequences? (4) Can demographic historical processes alone explain most of the observed differentiation on a genome-wide level or is it necessary to involve selection in their explanation?In general, our findings revealed that most genomic differentiation within D. melanogaster shows an out-of-Africa genetic signature. These results are inconsistent with the notion that most genomic differentiation occurs between cosmopolitan and Zimbabwean reproductively isolated races. Further, we found that the X is more differentiated between North American and African populations and more strongly deviates from pure neutrality in North American populations relative to autosomes. Nevertheless, our article shows that much of this deviation from neutrality is broadly consistent with several demographic null models, with a few notable exceptions. Athough this does not exclude selection as a possible alternative mechanism for the observed patterns, it supports the idea that most differentiation in D. melanogaster was likely driven by the sorting of African standing genetic variation into the New World. 相似文献
3.
4.
Inbreeding in highly selfing populations reduces effective size and, combined with demographic conditions associated with selfing, this can erode genetic diversity and increase population differentiation. Here we investigate the role that variation in mating patterns and demographic history play in shaping the distribution of nucleotide variation within and among populations of the annual neotropical colonizing plant Eichhornia paniculata, a species with wide variation in selfing rates. We sequenced 10 EST-derived nuclear loci in 225 individuals from 25 populations sampled from much of the geographic range and used coalescent simulations to investigate demographic history. Highly selfing populations exhibited moderate reductions in diversity but there was no significant difference in variation between outcrossing and mixed mating populations. Population size interacted strongly with mating system and explained more of the variation in diversity within populations. Bayesian structure analysis revealed strong regional clustering and selfing populations were highly differentiated on the basis of an analysis of Fst. There was no evidence for a significant loss of within-locus linkage disequilibrium within populations, but regional samples revealed greater breakdown in Brazil than in selfing populations from the Caribbean. Coalescent simulations indicate a moderate bottleneck associated with colonization of the Caribbean from Brazil ∼125,000 years before the present. Our results suggest that the recent multiple origins of selfing in E. paniculata from diverse outcrossing populations result in higher diversity than expected under long-term equilibrium.THE rate of self-fertilization in hermaphrodite organisms is expected to affect a number of important features of population genetic structure and diversity. Most directly, homozygosity increases as a function of the selfing rate and thus reduces the effective population size (Ne), up to twofold with complete selfing (Pollak 1987; Charlesworth et al. 1993; Nordborg 2000). Further, because of increased homozygosity, crossing over rarely occurs between heterozygous sites, thus increasing linkage disequilibrium (LD). Higher LD causes stronger hitchhiking effects such as selective sweeps, background selection, and Hill–Robertson interference, all of which are expected to further reduce the amount of neutral genetic variation within populations (reviewed in Charlesworth and Wright 2001).Population genetic processes resulting from inbreeding may be further augmented by demographic and life-history characteristics associated with the selfing habit. In particular, selfing populations can be founded by single individuals, resulting in striking reductions in diversity as a result of genetic bottlenecks and reproductive isolation. The capacity for uniparental reproduction gives many selfers prolific colonizing ability and the capacity to establish after long-distance dispersal, especially in comparison with obligate outcrossers (Baker 1955; Pannell and Barrett 1998). The colonization–extinction dynamics typical of many selfing species and limited pollen-mediated gene flow also increase differentiation among populations, resulting in considerable population subdivision (Hamrick and Godt 1990, 1996; Schoen and Brown 1991). Although the total amounts of among-population variation may be less affected by these processes (Pannell and Charlesworth 1999; Ingvarsson 2002), the demographic and life-history characteristics of many selfing species are likely to result in nonequilibrium conditions occurring in selfing populations.In many taxa where selfing has evolved it may be of relatively recent origin (Schoen et al. 1997; Takebayashi and Morrell 2001; Foxe et al. 2009; Guo et al. 2009). Where selfing has recently established, demographic forces associated with colonization may be as important as the mating system per se in structuring patterns of diversity. For example, if selfing originates through the establishment of a small number of founders, we would expect a sharp reduction in diversity relative to the outcrossing progenitor and a strong signature of a genetic bottleneck. In contrast, if selfing has evolved recently through the spread of genetic modifiers of small effect, newly established populations may retain significant amounts of ancestral polymorphism from their outcrossing progenitors. In this latter case populations may retain considerably more variation than expected under long-term equilibrium predictions.Molecular evidence for reduced nucleotide diversity and greater differentiation among populations of selfing taxa compared to populations of related outcrossing taxa has been reported from Leavenworthia (Liu et al. 1998, 1999), Arabidopsis (Savolainen et al. 2000; Wright et al. 2002), Solanum (Baudry et al. 2001), Mimulus (Sweigart and Willis 2003), Amsinckia (Perusse and Schoen 2004), and Caenorhabditis (Graustein et al. 2002; Cutter et al. 2006; Cutter 2008). In each case the reduction in diversity was more severe than the twofold reduction predicted for selfing populations at equilibrium. This indicates that factors in addition to the mating system are reducing diversity, but it has been difficult to uncouple the relative importance of genetic hitchhiking from the ecology and demographic history of selfing taxa. This challenge parallels similar difficulties in efforts to distinguish selective from demographic explanations in population genetic studies of Drosophila (Haddrill et al. 2005; Ometto et al. 2005; Thornton and Andolfatto 2006; Jensen et al. 2008). However, in many plant populations, especially those with annual life histories and small structured populations, demographic processes may play a more prominent role in causing reduced diversity than increased hitchhiking associated with selfing.Molecular population genetic studies of selfing in plants have generally focused on either small samples from a large number of populations (e.g., Sweigart and Willis 2003; Nordborg et al. 2005) or relatively large within-population samples from a small number of populations (e.g., Baudry et al. 2001). Ideally, a deeper sampling both within and among populations combined with independent ecological and historical information is required to improve understanding of the interplay of demographic and selective factors. Here we address these issues by examining patterns of nucleotide diversity within a large sample of populations of Eichhornia paniculata (Pontederiaceae), an annual species for which there is considerable ecological and demographic information (reviewed in Barrett and Husband 1997).E. paniculata occurs primarily in northeastern (N.E.) Brazil and the Caribbean islands of Cuba and Jamaica. Various lines of evidence suggest that Brazil is the original source region for Caribbean populations (reviewed in Barrett et al. 2009). Populations of E. paniculata exhibit striking mating-system diversity, ranging from predominantly outcrossing to those that are highly selfing (outcrossing rate, t = 0.002–0.96; n = 54 populations) (Barrett and Husband 1990; Barrett et al. 1992). Variation in mating system is associated with the evolutionary breakdown of the species'' tristylous genetic polymorphism and the spread and fixation of selfing variants capable of autonomous self-pollination (Barrett et al. 1989). Populations of E. paniculata are characterized by three morph structures: trimorphic with long-, mid-, and short-styled morphs (hereafter L-, M-, and S-morphs); dimorphic, with two floral morphs, most commonly the L- and M-morphs; and monomorphic, primarily composed of selfing variants of the M-morph. The morph structure and presence of selfing variants within populations explain ∼60% of the variation in outcrossing rates among populations (Barrett and Husband 1990). Trimorphic populations are largely outcrossing, dimorphic populations display mixed mating, and monomorphic populations are highly selfing. Patterns of allozyme variation indicate a reduction in diversity with increased selfing rates and greater among-population differentiation (Glover and Barrett 1987; Barrett and Husband 1990; Husband and Barrett 1993). Finally, studies of the inheritance of mating-system modifiers (Fenster and Barrett 1994; Vallejo-Marín and Barrett 2009) in combination with allozyme (Husband and Barrett 1993) and molecular evidence (Barrett et al. 2009) indicate that the transition from outcrossing to selfing in E. paniculata has occurred on multiple occasions.The goal of our study was to investigate the relation between mating-system variation and neutral molecular diversity for a large sample of E. paniculata populations encompassing most of the geographical range. This was accomplished by collecting multilocus nucleotide sequence data from 225 individuals sampled from 25 populations including trimorphic, dimorphic, and monomorphic populations. Because it has been previously demonstrated that this sequence of morph structures is strongly associated with increasing rates of self-fertilization (see Barrett and Husband 1990), we predicted a decrease in neutral diversity and increases in Fst and linkage disequilibrium from floral trimorphism to monomorphism. This extensive population-level sampling across a wide range of selfing rates allowed us to investigate the relative importance of mating system, geography, and current population size in structuring genetic variation. We also applied the approaches of Bayesian clustering (Pritchard et al. 2000; Falush et al. 2003; Gao et al. 2007) and divergence population genetics (Wakeley and Hey 1997; Hey and Nielsen 2004; Becquet and Przeworski 2007) to investigate the demographic history of E. paniculata and to provide a framework for understanding island colonization and the transition from outcrossing to selfing. 相似文献
5.
6.
Isabelle M. Henry Brian P. Dilkes Eric S. Miller Diana Burkart-Waco Luca Comai 《Genetics》2010,186(4):1231-1245
Aneuploid cells are characterized by incomplete chromosome sets. The resulting imbalance in gene dosage has phenotypic consequences that are specific to each karyotype. Even in the case of Down syndrome, the most viable and studied form of human aneuploidy, the mechanisms underlying the connected phenotypes remain mostly unclear. Because of their tolerance to aneuploidy, plants provide a powerful system for a genome-wide investigation of aneuploid syndromes, an approach that is not feasible in animal systems. Indeed, in many plant species, populations of aneuploid individuals can be easily obtained from triploid individuals. We phenotyped a population of Arabidopsis thaliana aneuploid individuals containing 25 different karyotypes. Even in this highly heterogeneous population, we demonstrate that certain traits are strongly associated with the dosage of specific chromosome types and that chromosomal effects can be additive. Further, we identified subtle developmental phenotypes expressed in the diploid progeny of aneuploid parent(s) but not in euploid controls from diploid lineages. These results indicate long-term phenotypic consequences of aneuploidy that can persist after chromosomal balance has been restored. We verified the diploid nature of these individuals by whole-genome sequencing and discuss the possibility that trans-generational phenotypic effects stem from epigenetic modifications passed from aneuploid parents to their diploid progeny.THE genome of aneuploid individuals contains incomplete chromosome sets. The balance between chromosome types, and the genes they encode, is compromised, resulting in altered expression of many genes, including genes with dosage-sensitive effects on phenotypes. In humans, only a few types of aneuploid karyotypes are viable (Hassold and Hunt 2001), highlighting the deleterious effect of chromosome imbalance. The most commonly known viable form of aneuploidy in humans is Down syndrome, which results from a trisomy of chromosome 21 in an otherwise diploid background. Down syndrome patients exhibit many specific phenotypes, sometimes visible only in a subset of patients (Antonarakis et al. 2004). For phenotypes found in all Down syndrome patients, the penetrance of each phenotype varies between patients (Antonarakis et al. 2004). Despite the increasing amount of information available about the human genome and the availability of a mouse model for Down syndrome (O''Doherty et al. 2005), the genes responsible for most of the phenotypes associated with Down syndrome are still unknown (Patterson 2007; Korbel et al. 2009; Patterson 2009). Recently, detailed phenotypic analyses of as many as 30 aneuploid patients have allowed the identification of susceptibility regions for several specific phenotypes (Patterson 2007, 2009; Korbel et al. 2009; Lyle et al. 2009), but the specific genes remain to be identified. Understanding the physiology of aneuploidy is not only relevant to those individuals with aneuploid genomes but also to understanding cancer since most cancerous cells are aneuploid (Matzke et al. 2003; Pihan and Doxsey 2003; Storchova and Pellman 2004; Holland and Cleveland 2009; Williams and Amon 2009) or the consequences of copy number variation and dosage sensitivity (Dear 2009; Henrichsen et al. 2009).Plants are more tolerant of aneuploidy than animals (Matzke et al. 2003) for reasons that remain unclear. Since the discovery of the Datura trisomic “chromosome mutants” by Blakeslee (1921, 1922), viable trisomics of each chromosome type have been described in numerous species. Trisomics exhibit phenotypes specific to the identity of the triplicated chromosome (Blakeslee 1922; Khush 1973; Koornneef and Van der Veen 1983; Singh 2003). More complex aneuploids, i.e., individuals carrying more than one additional chromosome, can be viable as well and have been observed in many plants species, especially among the progeny of triploid individuals (McClintock 1929; Levan 1942; Johnsson 1945; Khush 1973). Some species appear to be more tolerant of complex aneuploidies than others, suggesting a genetic basis for aneuploidy tolerance (Satina and Blakeslee 1938; Khush 1973; Ramsey and Schemske 2002; Henry et al. 2009). Aneuploid individuals frequently appear spontaneously within polyploid plant populations, presumably due to a failure to equally partition the multiple chromosome sets at meiosis (Randolph 1935; Doyle 1986). These aneuploids exhibit few or subtle phenotypic abnormalities and can often compete with their euploid progenitors (Ramsey and Schemske 1998). Plants therefore provide an excellent opportunity for a genome-wide investigation of aneuploid syndromes: sample size is not limited, phenotypes can be described and assessed in detail, and plant aneuploid populations provide a complex mixture of viable karyotypes.In this article, we report our investigation of the relationship between phenotype and karyotype in populations of aneuploid Arabidopsis thaliana plants. All simple trisomics of A. thaliana have been previously isolated and phenotypically characterized (Steinitz-Sears 1962; Lee-Chen and Steinitz-Sears 1967; Steinitz-Sears and Lee-Chen 1970; Koornneef and Van der Veen 1983), demonstrating that they are tolerated in A. thaliana. We previously reported that aneuploid swarms—populations of aneuploid individuals of varying aneuploid karyotypes—could be obtained from the progeny of triploid A. thaliana individuals (Henry et al. 2005, 2009). Using a combination of a quantitative PCR-based method and flow cytometry, we were able to derive the full aneuploid karyotype of each of these individuals (Henry et al. 2006). We further crossed triploid A. thaliana to diploid or tetraploid individuals and demonstrated that at least 44 of the 60 possible aneuploid karyotypes that could result from these crosses (aneuploid individuals carrying between 11 and 19 chromosomes) were viable and successfully produced adult plants. Taken together, these populations and methods make it possible to explore the basis of aneuploid syndromes in A. thaliana. In this study, we were able to phenotypically characterize at least one individual from 25 different aneuploid karyotypes falling between diploidy and tetraploidy. We demonstrated that specific phenotypes are affected by the dosage of specific chromosome types. The effect of the dosage of specific chromosome types on traits was additive and could be used to predict the observed phenotype. The availability of multiple generations of aneuploid and euploid individuals allowed us to investigate potential long-term effects of aneuploidy as well as parent-of-origin effects on aneuploid phenotypes. 相似文献
7.
A major question about cytokinesis concerns the role of the septin proteins, which localize to the division site in all animal and fungal cells but are essential for cytokinesis only in some cell types. For example, in Schizosaccharomyces pombe, four septins localize to the division site, but deletion of the four genes produces only a modest delay in cell separation. To ask if the S. pombe septins function redundantly in cytokinesis, we conducted a synthetic-lethal screen in a septin-deficient strain and identified seven mutations. One mutation affects Cdc4, a myosin light chain that is an essential component of the cytokinetic actomyosin ring. Five others cause frequent cell lysis during cell separation and map to two loci. These mutations and their dosage suppressors define a signaling pathway (including Rho1 and a novel arrestin) for repairing cell-wall damage. The seventh mutation affects the poorly understood RNA-binding protein Scw1 and severely delays cell separation when combined either with a septin mutation or with a mutation affecting the septin-interacting, anillin-like protein Mid2, suggesting that Scw1 functions in a pathway parallel to that of the septins. Taken together, our results suggest that the S. pombe septins participate redundantly in one or more pathways that cooperate with the actomyosin ring during cytokinesis and that a septin defect causes septum defects that can be repaired effectively only when the cell-integrity pathway is intact.THE fission yeast Schizosaccharomyces pombe provides an outstanding model system for studies of cytokinesis (McCollum and Gould 2001; Balasubramanian et al. 2004; Pollard and Wu 2010). As in most animal cells, successful cytokinesis in S. pombe requires an actomyosin ring (AMR). The AMR begins to assemble at the G2/M transition and involves the type II myosin heavy chains Myo2 and Myp2 and the light chains Cdc4 and Rlc1 (Wu et al. 2003). Myo2 and Cdc4 are essential for cytokinesis under all known conditions, Rlc1 is important at all temperatures but essential only at low temperatures, and Myp2 is essential only under stress conditions. As the AMR constricts, a septum of cell wall is formed between the daughter cells. The primary septum is sandwiched by secondary septa and subsequently digested to allow cell separation (Humbel et al. 2001; Sipiczki 2007). Because of the internal turgor pressure of the cells, the proper assembly and structural integrity of the septal layers are essential for cell survival.Septum formation involves the β-glucan synthases Bgs1/Cps1/Drc1, Bgs3, and Bgs4 (Ishiguro et al. 1997; Le Goff et al. 1999; Liu et al. 1999, 2002; Martín et al. 2003; Cortés et al. 2005) and the α-glucan synthase Ags1/Mok1 (Hochstenbach et al. 1998; Katayama et al. 1999). These synthases are regulated by the Rho GTPases Rho1 and Rho2 and the protein kinase C isoforms Pck1 and Pck2 (Arellano et al. 1996, 1997, 1999; Nakano et al. 1997; Hirata et al. 1998; Calonge et al. 2000; Sayers et al. 2000; Ma et al. 2006; Barba et al. 2008; García et al. 2009b). The Rho GTPases themselves appear to be regulated by both GTPase-activating proteins (GAPs) and guanine-nucleotide-exchange factors (GEFs) (Nakano et al. 2001; Calonge et al. 2003; Iwaki et al. 2003; Tajadura et al. 2004; Morrell-Falvey et al. 2005; Mutoh et al. 2005; García et al. 2006, 2009a,b). In addition, septum formation and AMR function appear to be interdependent. In the absence of a normal AMR, cells form aberrant septa and/or deposit septal materials at random locations, whereas a mutant defective in septum formation (bgs1) is also defective in AMR constriction (Gould and Simanis 1997; Le Goff et al. 1999; Liu et al. 1999, 2000). Both AMR constriction and septum formation also depend on the septation initiation network involving the small GTPase Spg1 (McCollum and Gould 2001; Krapp and Simanis 2008). Despite this considerable progress, many questions remain about the mechanisms and regulation of septum formation and its relationships to the function of the AMR.One major question concerns the role(s) of the septins. Proteins of this family are ubiquitous in fungal and animal cells and typically localize to the cell cortex, where they appear to serve as scaffolds and diffusion barriers for other proteins that participate in a wide variety of cellular processes (Longtine et al. 1996; Gladfelter et al. 2001; Hall et al. 2008; Caudron and Barral 2009). Despite the recent progress in elucidating the mechanisms of septin assembly (John et al. 2007; Sirajuddin et al. 2007; Bertin et al. 2008; McMurray and Thorner 2008), the details of septin function remain obscure. However, one prominent role of the septins and associated proteins is in cytokinesis. Septins concentrate at the division site in every cell type that has been examined, and in Saccharomyces cerevisiae (Hartwell 1971; Longtine et al. 1996; Lippincott et al. 2001; Dobbelaere and Barral 2004) and at least some Drosophila (Neufeld and Rubin 1994; Adam et al. 2000) and mammalian (Kinoshita et al. 1997; Surka et al. 2002) cell types, the septins are essential for cytokinesis. In S. cerevisiae, the septins are required for formation of the AMR (Bi et al. 1998; Lippincott and Li 1998). However, this cannot be their only role, because the AMR itself is not essential for cytokinesis in this organism (Bi et al. 1998; Korinek et al. 2000; Schmidt et al. 2002). Moreover, there is no evidence that the septins are necessary for AMR formation or function in any other organism. A further complication is that in some cell types, including most Caenorhabditis elegans cells (Nguyen et al. 2000; Maddox et al. 2007) and some Drosophila cells (Adam et al. 2000; Field et al. 2008), the septins do not appear to be essential for cytokinesis even though they localize to the division site.S. pombe has seven septins, four of which (Spn1, Spn2, Spn3, and Spn4) are expressed in vegetative cells and localize to the division site shortly before AMR constriction and septum formation (Longtine et al. 1996; Berlin et al. 2003; Tasto et al. 2003; Wu et al. 2003; An et al. 2004; Petit et al. 2005; Pan et al. 2007; Onishi et al. 2010). Spn1 and Spn4 appear to be the core members of the septin complex (An et al. 2004; McMurray and Thorner 2008), and mutants lacking either of these proteins do not assemble the others at the division site. Assembly of a normal septin ring also depends on the anillin-like protein Mid2, which colocalizes with the septins (Berlin et al. 2003; Tasto et al. 2003). Surprisingly, mutants lacking the septins are viable and form seemingly complete septa with approximately normal timing. These mutants do, however, display a variable delay in separation of the daughter cells, suggesting that the septins play some role(s) in the proper completion of the septum or in subsequent processes necessary for cell separation (Longtine et al. 1996; An et al. 2004; Martín-Cuadrado et al. 2005).It is possible that the septins localize to the division site and yet are nonessential for division in some cell types because their role is redundant with that of some other protein(s) or pathway(s). To explore this possibility in S. pombe, we screened for mutations that were lethal in combination with a lack of septins. The results suggest that the septins cooperate with the AMR during cytokinesis and that, in the absence of septin function, the septum is not formed properly, so that an intact system for recognizing and repairing cell-wall damage becomes critical for cell survival. 相似文献
8.
Age Structure,Changing Demography and Effective Population Size in Atlantic Salmon (Salmo salar)
下载免费PDF全文
![点击此处可从《Genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Effective population size (Ne) is a central evolutionary concept, but its genetic estimation can be significantly complicated by age structure. Here we investigate Ne in Atlantic salmon (Salmo salar) populations that have undergone changes in demography and population dynamics, applying four different genetic estimators. For this purpose we use genetic data (14 microsatellite markers) from archived scale samples collected between 1951 and 2004. Through life table simulations we assess the genetic consequences of life history variation on Ne. Although variation in reproductive contribution by mature parr affects age structure, we find that its effect on Ne estimation may be relatively minor. A comparison of estimator models suggests that even low iteroparity may upwardly bias Ne estimates when ignored (semelparity assumed) and should thus empirically be accounted for. Our results indicate that Ne may have changed over time in relatively small populations, but otherwise remained stable. Our ability to detect changes in Ne in larger populations was, however, likely hindered by sampling limitations. An evaluation of Ne estimates in a demographic context suggests that life history diversity, density-dependent factors, and metapopulation dynamics may all affect the genetic stability of these populations.THE effective size of a population (Ne) is an evolutionary parameter that can be informative on the strength of stochastic evolutionary processes, the relevance of which relative to deterministic forces has been debated for decades (e.g., Lande 1988). Stochastic forces include environmental, demographic, and genetic components, the latter two of which are thought to be more prominent at reduced population size, with potentially detrimental consequences for average individual fitness and population persistence (Newman and Pilson 1997; Saccheri et al. 1998; Frankham 2005). The quantification of Ne in conservation programs is thus frequently advocated (e.g., Luikart and Cornuet 1998; Schwartz et al. 2007), although gene flow deserves equal consideration given its countering effects on genetic stochasticity (Frankham et al. 2003; Palstra and Ruzzante 2008).Effective population size is determined mainly by the lifetime reproductive success of individuals in a population (Wright 1938; Felsenstein 1971). Variance in reproductive success, sex ratio, and population size fluctuations can reduce Ne below census population size (Frankham 1995). Given the difficulty in directly estimating Ne through quantification of these demographic factors (reviewed by Caballero 1994), efforts have been directed at inferring Ne indirectly through measurement of its genetic consequences (see Leberg 2005, Wang 2005, and Palstra and Ruzzante 2008 for reviews). Studies employing this approach have quantified historical levels of genetic diversity and genetic threats to population persistence (e.g., Nielsen et al. 1999b; Miller and Waits 2003; Johnson et al. 2004). Ne has been extensively studied in (commercially important) fish species, due to the common availability of collections of archived samples that facilitate genetic estimation using the temporal method (e.g., Hauser et al. 2002; Shrimpton and Heath 2003; Gomez-Uchida and Banks 2006; Saillant and Gold 2006).Most models relating Ne to a population''s genetic behavior make simplifying assumptions regarding population dynamics. Chiefly among these is the assumption of discrete generations, frequently violated in practice given that most natural populations are age structured with overlapping generations. Here, theoretical predictions still apply, provided that population size and age structure are constant (Felsenstein 1971; Hill 1972). Ignored age structure can introduce bias into temporal genetic methods for the estimation of Ne, especially for samples separated by time spans that are short relative to generation interval (Jorde and Ryman 1995; Waples and Yokota 2007; Palstra and Ruzzante 2008). Moreover, estimation methods that do account for age structure (e.g., Jorde and Ryman 1995) still assume this structure to be constant. Population dynamics will, however, likely be altered as population size changes, thus making precise quantifications of the genetic consequences of acute population declines difficult (Nunney 1993; Engen et al. 2005; Waples and Yokota 2007). This problem may be particularly relevant when declines are driven by anthropogenic impacts, such as selective harvesting regimes, that can affect age structure and Ne simultaneously (Ryman et al. 1981; Allendorf et al. 2008). Demographic changes thus have broad conservation implications, as they can affect a population''s sensitivity to environmental stochasticity and years of poor recruitment (Warner and Chesson 1985; Ellner and Hairston 1994; Gaggiotti and Vetter 1999). Consequently, although there is an urgent need to elucidate the genetic consequences of population declines, relatively little is understood about the behavior of Ne when population dynamics change (but see Engen et al. 2005, 2007).Here we focus on age structure and Ne in Atlantic salmon (Salmo salar) river populations in Newfoundland and Labrador. The freshwater habitat in this part of the species'' distribution range is relatively pristine (Parrish et al. 1998), yet Atlantic salmon in this area have experienced demographic declines, associated with a commercial marine fishery, characterized by high exploitation rates (40–80% of anadromous runs; Dempson et al. 2001). A fishery moratorium was declared in 1992, with rivers displaying differential recovery patterns since then (Dempson et al. 2004b), suggesting a geographically variable impact of deterministic and stochastic factors, possibly including genetics. An evaluation of those genetic consequences thus requires accounting for potential changes in population dynamics as well as in life history. Life history in Atlantic salmon can be highly versatile (Fleming 1996; Hutchings and Jones 1998; Fleming and Reynolds 2004), as exemplified by the high variation in age-at-maturity displayed among and within populations (Hutchings and Jones 1998), partly reflecting high phenotypic plasticity (Hutchings 2004). This diversity is particularly evident in the reproductive biology of males, which can mature as parr during juvenile freshwater stages (Jones and King 1952; Fleming and Reynolds 2004) and/or at various ages as anadromous individuals, when returning to spawn in freshwater from ocean migration. Variability in life history strategies is further augmented by iteroparity, which can be viewed as a bet-hedging strategy to deal with environmental uncertainty (e.g., Orzack and Tuljapurkar 1989; Fleming and Reynolds 2004). Life history diversity and plasticity may allow salmonid fish populations to alter and optimize their life history under changing demography and population dynamics, potentially acting to stabilize Ne. Reduced variance in individual reproductive success at low breeder abundance (genetic compensation) will achieve similar effects and might be a realistic aspect of salmonid breeding systems (Ardren and Kapuscinski 2003; Fraser et al. 2007b). Little is currently known about the relationships between life history plasticity, demographic change and Ne, partly due to scarcity of the multivariate data required for these analyses.Our objective in this article is twofold. First, we use demographic data for rivers in Newfoundland to quantify how life history variation influences age structure in Atlantic salmon and hence Ne and its empirical estimation from genetic data. We find that variation in reproductive contribution by mature parr has a much smaller effect on the estimation of Ne than is often assumed. Second, we use temporal genetic data to estimate Ne and quantify the genetic consequences of demographic changes. We attempt to account for potential sources of bias, associated with (changes in) age structure and life history, by using four different analytical models to estimate Ne: a single-sample estimator using the linkage disequilibrium method (Hill 1981), the temporal model assuming discrete generations (Nei and Tajima 1981; Waples 1989), and two temporal models for species with overlapping generations (Waples 1990a,b; Jorde and Ryman 1995) that differ principally in assumptions regarding iteroparity. A comparison of results from these different estimators suggests that iteroparity may often warrant analytical consideration, even when it is presumably low. Although sometimes limited by statistical power, a quantification and comparison of temporal changes in Ne among river populations suggests a more prominent impact of demographic changes on Ne in relatively small river populations. 相似文献
9.
John R. Stinchcombe Cynthia Weinig Katy D. Heath Marcus T. Brock Johanna Schmitt 《Genetics》2009,182(3):911-922
The importance of genes of major effect for evolutionary trajectories within and among natural populations has long been the subject of intense debate. For example, if allelic variation at a major-effect locus fundamentally alters the structure of quantitative trait variation, then fixation of a single locus can have rapid and profound effects on the rate or direction of subsequent evolutionary change. Using an Arabidopsis thaliana RIL mapping population, we compare G-matrix structure between lines possessing different alleles at ERECTA, a locus known to affect ecologically relevant variation in plant architecture. We find that the allele present at ERECTA significantly alters G-matrix structure—in particular the genetic correlations between branch number and flowering time traits—and may also modulate the strength of natural selection on these traits. Despite these differences, however, when we extend our analysis to determine how evolution might differ depending on the ERECTA allele, we find that predicted responses to selection are similar. To compare responses to selection between allele classes, we developed a resampling strategy that incorporates uncertainty in estimates of selection that can also be used for statistical comparisons of G matrices.THE structure of the genetic variation that underlies phenotypic traits has important consequences for understanding the evolution of quantitative traits (Fisher 1930; Lande 1979; Bulmer 1980; Kimura 1983; Orr 1998; Agrawal et al. 2001). Despite the infinitesimal model''s allure and theoretical tractability (see Orr and Coyne 1992; Orr 1998, 2005a,b for reviews of its influence), evidence has accumulated from several sources (artificial selection experiments, experimental evolution, and QTL mapping) to suggest that genes of major effect often contribute to quantitative traits. Thus, the frequency and role of genes of major effect in evolutionary quantitative genetics have been a subject of intense debate and investigation for close to 80 years (Fisher 1930; Kimura 1983; Orr 1998, 2005a,b). Beyond the conceptual implications, the prevalence of major-effect loci also affects our ability to determine the genetic basis of adaptations and species differences (e.g., Bradshaw et al. 1995, 1998).Although the existence of genes of major effect is no longer in doubt, we still lack basic empirical data on how segregating variation at such genes affects key components of evolutionary process (but see Carrière and Roff 1995). In other words, How does polymorphism at genes of major effect alter patterns of genetic variation and covariation, natural selection, and the likely response to selection? The lack of data stems, in part, from the methods used to detect genes of major effect: experimental evolution (e.g., Bull et al. 1997; Zeyl 2005) and QTL analysis (see Erickson et al. 2004 for a review) often detect such genes retrospectively after they have become fixed in experimental populations or the species pairs used to generate the mapping population. The consequences of polymorphism at these genes on patterns of variation, covariation, selection, and the response to selection—which can be transient (Agrawal et al. 2001)—are thus often unobserved.A partial exception to the absence of data on the effects of major genes comes from artificial selection experiments, in which a substantial evolutionary response to selection in the phenotype after a plateau is often interpreted as evidence for the fixation of a major-effect locus (Frankham et al. 1968; Yoo 1980a,b; Frankham 1980; Shrimpton and Robertson 1988a,b; Caballero et al. 1991; Keightley 1998; see Mackay 1990 and Hill and Caballero 1992 for reviews). However, many of these experiments report only data on the selected phenotype (e.g., bristle number) or, alternatively, the selected phenotype and some measure of fitness (e.g., Frankham et al. 1968, Yoo 1980b; Caballero et al. 1991; Mackay et al. 1994; Fry et al. 1995; Nuzhdin et al. 1995; Zur Lage et al. 1997), making it difficult to infer how a mutation will affect variation, covariation, selection, and evolutionary responses for a suite of traits that might affect fitness themselves. One approach is to document how variation at individual genes of major effect affects the genetic variance–covariance matrix (“G matrix”; Lande 1979), which represents the additive genetic variance and covariance between traits.Although direct evidence for variation at major-effect genes altering patterns of genetic variation, covariation, and selection is rare, there is abundant evidence for the genetic mechanisms that could produce these dynamics. A gene of major effect could have these consequences due to any of at least three genetic mechanisms: (1) pleiotropy, where a gene of major effect influences several traits, including potentially fitness, simultaneously, (2) physical linkage or linkage disequilibrium (LD), in which a gene of major effect is either physically linked or in LD with other genes that influence other traits under selection, and (3) epistasis, in which the allele present at a major-effect gene alters the phenotypic effect of other loci and potentially phenotypes under selection. Evidence for these three evolutionary genetic mechanisms leading to changes in suites of traits comes from a variety of sources, including mutation accumulation experiments (Clark et al. 1995; Fernandez and Lopez-Fanjul 1996), mutation induction experiments (Keightley and Ohnishi 1998), artificial selection experiments (Long et al. 1995), and transposable element insertions (Rollmann et al. 2006). For pleiotropy in particular, major-effect genes that have consequences on several phenotypic traits are well known from the domestication and livestock breeding literature [e.g., myostatin mutations in Belgian blue cattle and whippets (Arthur 1995; Grobet et al. 1997; Mosher et al. 2007), halothane genes in pigs (Christian and Rothschild 1991; Fujii et al. 1991), and Booroola and Inverdale genes in sheep (Amer et al. 1999; Visscher et al. 2000)]. While these data suggest that variation at major-effect genes could—and probably does—influence variation, covariation, and selection on quantitative traits, data on the magnitude of these consequences remain lacking.Recombinant inbred line (RIL) populations are a promising tool for investigating the influence of major-effect loci. During advancement of the lines from F2''s to RILs, alternate alleles at major-effect genes (and most of the rest of the genome) will be made homozygous, simplifying comparisons among genotypic classes. Because of the high homozygosity, individuals within RILs are nearly genetically identical, facilitating phenotyping of many genotypes under a range of environments. In addition, because of recombination, alternative alleles are randomized across genetic backgrounds—facilitating robust comparisons between sets of lines differing at a major-effect locus.Here we investigate how polymorphism at an artificially induced mutation, the erecta locus in Arabidopsis thaliana, affects the magnitude of these important evolutionary genetic parameters under ecologically realistic field conditions. We use the Landsberg erecta (Ler) × Columbia (Col) RIL population of A. thaliana to examine how variation at a gene of major effect influences genetic variation, covariation, and selection on quantitative traits in a field setting. The Ler × Col RIL population is particularly suitable, because it segregates for an artificially induced mutation at the erecta locus, which has been shown to influence a wide variety of plant traits. The Ler × Col population thus allows a powerful test of the effects of segregating variation at a gene—chosen a priori—with numerous pleiotropic effects. The ERECTA gene is a leucine-rich receptor-like kinase (LRR-RLK) (Torii et al. 1996) and has been shown to affect plant growth rates (El-Lithy et al. 2004), stomatal patterning and transpiration efficiency (Masle et al. 2005; Shpak et al. 2005), bacterial pathogen resistance (Godiard et al. 2003), inflorescence and floral organ size and shape (Douglas et al. 2002; Shpak et al. 2003, 2004), and leaf polarity (Xu et al. 2003; Qi et al. 2004).Specifically, we sought to answer the following questions: (1) Is variation at erecta significantly associated with changes to the G matrix? (2) Is variation at erecta associated with changes in natural selection on genetically variable traits? And (3) is variation at erecta associated with significantly different projected evolutionary responses to selection? 相似文献
10.
11.
12.
13.
Unraveling the Complex Trait of Crop Yield With Quantitative Trait Loci Mapping in Brassica napus 总被引:1,自引:0,他引:1
Jiaqin Shi Ruiyuan Li Dan Qiu Congcong Jiang Yan Long Colin Morgan Ian Bancroft Jianyi Zhao Jinling Meng 《Genetics》2009,182(3):851-861
Yield is the most important and complex trait for the genetic improvement of crops. Although much research into the genetic basis of yield and yield-associated traits has been reported, in each such experiment the genetic architecture and determinants of yield have remained ambiguous. One of the most intractable problems is the interaction between genes and the environment. We identified 85 quantitative trait loci (QTL) for seed yield along with 785 QTL for eight yield-associated traits, from 10 natural environments and two related populations of rapeseed. A trait-by-trait meta-analysis revealed 401 consensus QTL, of which 82.5% were clustered and integrated into 111 pleiotropic unique QTL by meta-analysis, 47 of which were relevant for seed yield. The complexity of the genetic architecture of yield was demonstrated, illustrating the pleiotropy, synthesis, variability, and plasticity of yield QTL. The idea of estimating indicator QTL for yield QTL and identifying potential candidate genes for yield provides an advance in methodology for complex traits.YIELD is the most important and complex trait in crops. It reflects the interaction of the environment with all growth and development processes that occur throughout the life cycle (Quarrie et al. 2006). Crop yield is directly and multiply determined by yield-component traits (such as seed weight and seed number). Yield-related traits (such as biomass, harvest index, plant architecture, adaptation, resistance to biotic and abiotic constraints) may also indirectly affect yield by affecting the yield-component traits or by other, unknown mechanisms. Increasing evidence suggests that “fine-mapped” quantitative trait loci (QTL) or genes identified as affecting crop yield involve diverse pathways, such as seed number (Ashikari et al. 2005; Tian et al. 2006b; Burstin et al. 2007; Xie et al. 2008; Xing et al. 2008; Xue et al. 2008), seed weight (Ishimaru 2003; Song et al. 2005; Shomura et al. 2008; Wang et al. 2008; Xie et al. 2006, 2008; Xing et al. 2008; Xue et al. 2008), flowering time (Cockram et al. 2007; Song et al. 2007; Xie et al. 2008; Xue et al. 2008), plant height (Salamini 2003; Ashikari et al. 2005; Xie et al. 2008; Xue et al. 2008), branching (Clark et al. 2006; Burstin et al. 2007; Xing et al. 2008), biomass yield (Quarrie et al. 2006; Burstin et al. 2007), resistance and tolerance to biotic and abiotic stresses (Khush 2001; Brown 2002; Yuan et al. 2002; Waller et al. 2005; Zhang 2007; Warrington et al. 2008), and root architecture (Hochholdinger et al. 2008).Many experiments have explored the genetic basis of yield and yield-associated traits (yield components and yield-related traits) in crops. Summaries of identified QTL have been published for wheat (MacCaferri et al. 2008), barley (Von Korff et al. 2008), rice, and maize (http://www.gramene.org/). The results show several common patterns. First, QTL for yield and yield-associated traits tend to be clustered in the genome, which suggests that the QTL of the yield-associated traits have pleiotropic effects on yield. Second, this kind of pleiotropy has not been well analyzed genetically. The QTL for yield (complicated factor), therefore, have not been associated with any yield-associated traits (relatively simple factors, such as plant height). Therefore, they are unlikely to predict accurately potential candidate genes for yield. Third, only a few loci (rarely >10) have been found for each of these traits. Thus, the genetic architecture of yield has remained ambiguous. Fourth, trials were carried out in a few environments and how the mode of expression of QTL for these complex traits might respond in different environments is unclear.In this study, the genetic architecture of crop yield was analyzed through the QTL mapping of seed yield and eight yield-associated traits in two related populations of rapeseed (Brassica napus) that were grown in 10 natural environments. The complexity of the genetic architecture of seed yield was demonstrated by QTL meta-analysis. The idea of estimating indicator QTL (QTL of yield-associated traits, which are defined as the potential genetic determinants of the colocalized QTL for yield) for yield QTL in conjunction with the identification of candidate genes is described. 相似文献
14.
The coalescent with recombination is a very useful tool in molecular population genetics. Under this framework, genealogies often represent the evolution of the substitution unit, and because of this, the few coalescent algorithms implemented for the simulation of coding sequences force recombination to occur only between codons. However, it is clear that recombination is expected to occur most often within codons. Here we have developed an algorithm that can evolve coding sequences under an ancestral recombination graph that represents the genealogies at each nucleotide site, thereby allowing for intracodon recombination. The algorithm is a modification of Hudson''s coalescent in which, in addition to keeping track of events occurring in the ancestral material that reaches the sample, we need to keep track of events occurring in ancestral material that does not reach the sample but that is produced by intracodon recombination. We are able to show that at typical substitution rates the number of nonsynonymous changes induced by intracodon recombination is small and that intracodon recombination does not generally result in inflated estimates of the overall nonsynonymous/synonymous substitution ratio (ω). On the other hand, recombination can bias the estimation of ω at particular codons, resulting in apparent rate variation among sites and in the spurious identification of positively selected sites. Importantly, in this case, allowing for variable synonymous rates across sites greatly reduces the false-positive rate and recovers statistical power. Finally, coalescent simulations with intracodon recombination could be used to better represent the evolution of nuclear coding genes or fast-evolving pathogens such as HIV-1.We have implemented this algorithm in a computer program called NetRecodon, freely available at http://darwin.uvigo.es.THE coalescent (Kingman 1982; Hudson 1990) provides an efficient sampling of genealogical histories from a theoretical population evolving under a neutral Wright–Fisher model (Ewens 1979; Kingman 1982; Hudson 1990). Coalescent simulations are commonly used in molecular population genetics to understand the behavior and interactions among evolutionary processes under different scenarios (Innan et al. 2005), such as hypothesis testing (DeChaine and Martin 2006), evaluation and comparison of different analytical methods (Carvajal-Rodriguez et al. 2006), or estimation of population genetic parameters (Beaumont et al. 2002). Indeed, to obtain meaningful biological inferences from these simulations, it is very important that the underlying model is as realistic as possible. In this regard, a number of models have been developed during the last decade that consider different evolutionary processes such as recombination (Simonsen and Churchill 1997; Wiuf and Posada 2003), gene conversion (Wiuf and Hein 2000), selection (Hudson and Kaplan 1988, 1995), and gene flow or demographic history (Slatkin 1987; Pybus and Rambaut 2002).Despite these advances, and in the face of a plethora of coalescent simulators (Excoffier et al. 2000; Hudson 2002; Posada and Wiuf 2003; Spencer and Coop 2004; Mailund et al. 2005; Schaffner et al. 2005; Marjoram and Wall 2006; Arenas and Posada 2007; Hellenthal and Stephens 2007; Liang et al. 2007), it was not possible until very recently to simulate recombining protein-coding DNA sequences within this framework (Anisimova et al. 2003; Arenas and Posada 2007). Importantly, to our knowledge, the algorithms described or implemented so far allow recombination only between codons, not within them. The reason for this unrealistic constraint is that standard codon models describe the probabilities of change along a lineage from one codon to another (Yang 2006), whereas recombination can occur between any two nucleotides, potentially resulting in one or more lineages not being shared by all the positions of the codon. In other words, although the unit for substitution in coding sequences is the codon, the unit for recombination in these sequences is still the nucleotide. Here we describe a new algorithm that overcomes this limitation by allowing for the evolution of different positions of the same codon in distinct genealogies. Furthermore, we use this algorithm to evaluate the effect of intracodon recombination on the generation of nonsynonymous (NS) diversity and on the estimation of the ratio of nonsynonymous-to-synonymous substitution rates (ω or dN/dS) (Li and Gojobori 1983) and the hypotheses derived from it. 相似文献
15.
Christian Lexer Jeffrey A. Joseph Marcela van Loo Thelma Barbará Berthold Heinze Denes Bartha Stefano Castiglione Michael F. Fay C. Alex Buerkle 《Genetics》2010,186(2):699-712
Admixture between genetically divergent populations facilitates genomic studies of the mechanisms involved in adaptation, reproductive isolation, and speciation, including mapping of the loci involved in these phenomena. Little is known about how pre- and postzygotic barriers will affect the prospects of “admixture mapping” in wild species. We have studied 93 mapped genetic markers (microsatellites, indels, and sequence polymorphisms, ∼60,000 data points) to address this topic in hybrid zones of Populus alba and P. tremula, two widespread, ecologically important forest trees. Using genotype and linkage information and recently developed analytical tools we show that (1) reproductive isolation between these species is much stronger than previously assumed but this cannot prevent the introgression of neutral or advantageous alleles, (2) unexpected genotypic gaps exist between recombinant hybrids and their parental taxa, (3) these conspicuous genotypic patterns are due to assortative mating and strong postzygotic barriers, rather than recent population history. We discuss possible evolutionary trajectories of hybrid lineages between these species and outline strategies for admixture mapping in hybrid zones between highly divergent populations. Datasets such as this one are still rare in studies of natural hybrid zones but should soon become more common as high throughput genotyping and resequencing become feasible in nonmodel species.ADMIXTURE or hybrid zones between genetically divergent populations are increasingly being explored for their use in studies of adaptation, reproductive isolation, and speciation (Rieseberg et al. 1999; Martinsen et al. 2001; Wu 2001; Vines et al. 2003; Payseur et al. 2004; reviewed by Coyne and Orr 2004), especially for their potential in identifying recombinants for gene mapping (otherwise known as “admixture mapping”; Chakraborty and Weiss 1988; Briscoe et al. 1994; Rieseberg et al. 1999; Reich et al. 2005; Slate 2005; Zhu et al. 2005; Lexer et al. 2007; Nolte et al. 2009). In many taxa of animals and plants, recombinants are created by admixture between divergent populations or species in hybrid zones or ecotones (Buerkle and Lexer 2008; Gompert and Buerkle 2009). The growing interest of evolutionary geneticists in admixture has its roots in both basic evolutionary genetics and breeding.With respect to evolutionary genetics, admixed populations have been viewed as important resources for studying the genetics of adaptation and speciation, since the discovery that by fitting geographical clines of allele frequencies across hybrid zones, the strength of intrinsic and extrinsic (ecological) barriers to gene flow can be estimated (Barton and Hewitt 1985; Barton and Gale 1993). More recently, the genomics era has taken these concepts to a new level by providing genetic or physical genome maps for many species so that clines or introgression patterns of individual loci can be compared to their genomic background (see below; Falush et al. 2003; Gompert and Buerkle 2009). Thus, hybrid zones permit the identification and study of quantitative trait loci (QTL), genes, or other genetic elements involved in reproductive isolation and speciation in situ, directly in natural populations, if sufficient genetic recombination has occurred (Rieseberg and Buerkle 2002). In applied genetics, studies of hybrid zones yield information on the genomic architecture of barriers to introgression, which is of great interest to breeders concerned with the establishment of pedigrees for tree selection and domestication (Stettler et al. 1996).Most animal or plant hybrid zones studied to date involve hybridization between parental populations that are much more divergent than the admixed human populations that have been used successfully for gene mapping in human medical genetics (e.g., Reich et al. 2005; Zhu et al. 2005). Little experience exists with interpreting genomic patterns of ancestry and admixture in such highly divergent, nonhuman populations. Early genomic work on hybrid zones, based on dominant genetic markers, suggested the feasibility of mapping genome regions involved in reproductive isolation and speciation (Rieseberg et al. 1999; Rogers et al. 2001), but these studies did not allow tests for selection on genotypes at single loci in different genomic backgrounds. This became possible only recently due to the development of novel analytical tools suited to large numbers of codominant markers, especially linkage models of Bayesian admixture analysis (Falush et al. 2003, 2007) and methods to fit “genomic clines” of codominant marker genotypes across complete genomic admixture gradients (Lexer et al. 2007; Gompert and Buerkle 2009; Nolte et al. 2009; Teeter et al. 2010). Great advances also have been made in interpreting single-locus estimates of genetic divergence between populations and species (Beaumont 2005; Foll and Gaggiotti 2008; Excoffier et al. 2009a). Here, we bring these approaches together to yield novel insights into genomic patterns of reproductive isolation and mating in hybrid zones of two widespread and important members of the “model tree” genus Populus. Our goal was to infer patterns of reproductive isolation and the likely evolutionary trajectories of hybrid populations and to develop strategies for genetic mapping in admixed populations.Populus alba (white poplar) and P. tremula (European aspen) are ecologically divergent (floodplain vs. upland habitat) hybridizing tree species related to P. trichocarpa, the first completely sequenced forest tree (Tuskan et al. 2006). The two species are highly differentiated for neutral DNA-based markers (Lexer et al. 2007) and numerous phenotypic and ecological traits (Lexer et al. 2009). Mosaic hybrid zones between these species often form in riparian habitats (Lexer et al. 2005; hybrids sometimes referred to as P. × canescens) and have been proposed as potential “mapping populations” for identifying QTL and genes of interest in evolutionary biology (Lexer et al. 2007; Buerkle and Lexer 2008) and breeding (Fossati et al. 2004; Lexer et al. 2004). Previous studies of these hybrid zones were conducted with a relatively small number of genetic markers and without making use of linkage information; the genomic composition of hybrid zones between these species has never been studied with a genomewide panel of codominant markers with known linkage relationships. Specifically, we address the following questions in this contribution:(1) What does an analysis of admixture and differentiation based on a genome-wide panel of mapped markers tell us about patterns of reproductive isolation and mating in hybrid zones of European Populus species? (2) What are the likely roles of pre- and postzygotic barriers vs. recent, localized historical factors in generating the observed genomic patterns? (3) What are the practical implications for admixture mapping in hybrid zones between highly divergent populations? We showcase where the genetic peculiarities of hybrid zones will limit their use for gene mapping and where they suggest new approaches that were perhaps not foreseen by geneticists with a focus on human medical applications. 相似文献
16.
17.
Association Genetics of Coastal Douglas Fir (Pseudotsuga menziesii var. menziesii,Pinaceae). I. Cold-Hardiness Related Traits
下载免费PDF全文
![点击此处可从《Genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Andrew J. Eckert Andrew D. Bower Jill L. Wegrzyn Barnaly Pande Kathleen D. Jermstad Konstantin V. Krutovsky J. Bradley St. Clair David B. Neale 《Genetics》2009,182(4):1289-1302
18.
We consider a population that adapts to a gradually changing environment. Our aim is to describe how ecological and genetic factors combine to determine the genetic basis of adaptation. Specifically, we consider the evolution of a polygenic trait that is under stabilizing selection with a moving optimum. The ecological dynamics are defined by the strength of selection, , and the speed of the optimum, ; the key genetic parameters are the mutation rate Θ and the variance of the effects of new mutations, ω. We develop analytical approximations within an “adaptive-walk” framework and describe how selection acts as a sieve that transforms a given distribution of new mutations into the distribution of adaptive substitutions. Our analytical results are complemented by individual-based simulations. We find that (i) the ecological dynamics have a strong effect on the distribution of adaptive substitutions and their impact depends largely on a single composite measure , which combines the ecological and genetic parameters; (ii) depending on γ, we can distinguish two distinct adaptive regimes: for large γ the adaptive process is mutation limited and dominated by genetic constraints, whereas for small γ it is environmentally limited and dominated by the external ecological dynamics; (iii) deviations from the adaptive-walk approximation occur for large mutation rates, when different mutant alleles interact via linkage or epistasis; and (iv) in contrast to predictions from previous models assuming constant selection, the distribution of adaptive substitutions is generally not exponential.AN important aim for both empirical and theoretical evolutionary biologists is to better understand the genetics of adaptation (e.g., Orr 2005a). For example, among the multitude of mutations that arise in a population, which ones are eventually fixed and contribute to evolutionary change? That is, given a distribution of new mutations, what is the distribution of adaptive substitutions (or fixed mutations)? Here, distribution means the probability distribution of the effects of mutations on either the phenotype or the fitness of their carriers. In principle, both the distribution of new mutations and the distribution of adaptive substitutions can be measured empirically, the former from mutation accumulation experiments (Eyre-Walker and Keightley 2007) and the latter from QTL (e.g., Bradshaw et al. 1998) or experimental evolution (Elena and Lenski 2003) studies. However, as only a small subset of all mutations is beneficial, such measurements are difficult. Therefore, a large role in studying the genetics of adaptation has to be played by theoretical modeling.In recent years, several different approaches have emerged for modeling the process of adaptation. Considerable work exists, in particular, in the context of Fisher''s geometric model (e.g., Fisher 1930; Kimura 1983; Orr 1998; Welch and Waxman 2005; Martin and Lenormand 2006), Gillespie''s mutational landscape model (e.g., Gillespie 1983, 1984; Orr 2002), various models of so-called “adaptive walks” on rugged fitness landscapes (e.g., Kauffman and Levin 1987; Kauffman 1993), and models of clonal interference in asexual populations (e.g., Gerrish and Lenski 1998; Park and Krug 2007). Together, these models have yielded several robust predictions. For example, both Fisher''s geometric model and the mutational landscape model predict that the distribution of adaptive substitutions should be approximately exponential (with respect to either phenotype or fitness) (Orr 1998, 2002, 2005a,b). This means that most substitutions have little effect, but that a significant fraction of the overall evolutionary change is due to a small number of substitutions with large effects. These results are in qualitative agreement with empirical data (Orr 2005a; Elena and Lenski 2003) and have shed new light on the classical debate about micro- vs. macromutationalism (Fisher 1930; Provine 2001).One way to look at adaptation is to view selection as a sieve that transforms the distribution of new mutations into the distribution of adaptive substitutions (Turner 1981; Orr and Betancourt 2001). This perspective emphasizes the role of environmental factors and directly leads to the question of how different selective regimes (sieves) affect the adaptive process. Yet, almost all studies to date have focused on the simplest possible ecological scenario: a population that, after a sudden change in the environment, is now under constant stabilizing selection.In reality, however, environmental change is often gradual rather than sudden (e.g., Hairston et al. 2005; Thompson 2005; Parmesan 2006; Perron et al. 2008). To account for this possibility, several authors (Bello and Waxman 2006; Collins et al. 2007; Kopp and Hermisson 2007; Sato and Waxman 2008; Kopp and Hermisson 2009) have recently turned to the so-called moving optimum model, which was originally devised in the field of quantitative genetics (e.g., Lynch et al. 1991; Lynch and Lande 1993; Bürger and Lynch 1995; Bürger 1999; Waxman and Peck 1999; Bürger and Gimelfarb 2002; Nunney 2003; Jones et al. 2004). In this model, the selectively favored value of a quantitative trait changes over time, such that the trait is under a mixture of stabilizing and directional selection. An important aspect of the moving optimum model is that it introduces an additional timescale (the timescale of environmental change), which is absent in the previous models.In a recent article (Kopp and Hermisson 2009) and a previous note (Kopp and Hermisson 2007), we have used the moving optimum model to investigate the time to fixation of a single mutation and the order in which mutations of different phenotypic effect go to fixation. However, the fastest mutations in the short term are not necessarily those that dominate evolution in the long term. The present article focuses on this long-term evolution, which can be characterized by the distribution of adaptive substitutions. 相似文献
19.