A Novel Candidate Region for Genetic Adaptation to High Altitude in Andean Populations

Humans living at high altitude (≥2,500 meters above sea level) have acquired unique abilities to survive the associated extreme environmental conditions, including hypoxia, cold temperature, limited food availability and high levels of free radicals and oxidants. Long-term inhabitants of the most elevated regions of the world have undergone extensive physiological and/or genetic changes, particularly in the regulation of respiration and circulation, when compared to lowland populations. Genome scans have identified candidate genes involved in altitude adaption in the Tibetan Plateau and the Ethiopian highlands, in contrast to populations from the Andes, which have not been as intensively investigated. In the present study, we focused on three indigenous populations from Bolivia: two groups of Andean natives, Aymara and Quechua, and the low-altitude control group of Guarani from the Gran Chaco lowlands. Using pooled samples, we identified a number of SNPs exhibiting large allele frequency differences over 900,000 genotyped SNPs. A region in chromosome 10 (within the cytogenetic bands q22.3 and q23.1) was significantly differentiated between highland and lowland groups. We resequenced ~1.5 Mb surrounding the candidate region and identified strong signals of positive selection in the highland populations. A composite of multiple signals like test localized the signal to FAM213A and a related enhancer; the product of this gene acts as an antioxidant to lower oxidative stress and may help to maintain bone mass. The results suggest that positive selection on the enhancer might increase the expression of this antioxidant, and thereby prevent oxidative damage. In addition, the most significant signal in a relative extended haplotype homozygosity analysis was localized to the SFTPD gene, which encodes a surfactant pulmonary-associated protein involved in normal respiration and innate host defense. Our study thus identifies two novel candidate genes and associated pathways that may be involved in high-altitude adaptation in Andean populations.     

Men Traveling Away from Home Are More Likely to Bring Malaria into High Altitude Villages,Northwest Ethiopia

Background

Information about malaria risk factors at high altitudes is scanty. Understanding the risk factors that determine the risk of malaria transmission at high altitude villages is important to facilitate implementing sustainable malaria control and prevention programs.

Methods

An unmatched case control study was conducted among patients seeking treatment at health centers in high altitude areas. Either microscopy or rapid diagnostic tests were used to confirm the presence of plasmodium species. A generalized linear model was used to identify the predictors of malaria transmission in high altitude villages.

Results

Males (AOR = 3.11, 95%CI: 2.28, 4.23), and those who traveled away from the home in the previous month (AOR = 2.01, 95% CI: 1.56, 2.58) were strongly associated with presence of malaria in high altitude villages. Other significant factors, including agriculture in occupation (AOR = 1.41, 95% CI: 1.05, 1.93), plants used for fencing (AOR = 1.70, 95% CI: 1.18, 2.52) and forests near the house (AOR = 1.60, 95% CI: 1.15, 2.47), were found predictors for malaria in high altitude villages.

Conclusion

Travel outside of their home was an important risk of malaria infections acquisition. Targeting males who frequently travel to malarious areas can reduce malaria transmission risks in high altitude areas.     

The Complete Genome of Comamonas testosteroni Reveals Its Genetic Adaptations to Changing Environments

Members of the gram-negative, strictly aerobic genus Comamonas occur in various environments. Here we report the complete genome of Comamonas testosteroni strain CNB-2. Strain CNB-2 has a circular chromosome that is 5,373,643 bp long and has a G+C content of 61.4%. A total of 4,803 open reading frames (ORFs) were identified; 3,514 of these ORFs are functionally assigned to energy production, cell growth, signal transduction, or transportation, while 866 ORFs encode hypothetical proteins and 423 ORFs encode purely hypothetical proteins. The CNB-2 genome has many genes for transportation (22%) and signal transduction (6%), which allows the cells to respond and adapt to changing environments. Strain CNB-2 does not assimilate carbohydrates due to the lack of genes encoding proteins involved in glycolysis and pentose phosphate pathways, and it contains many genes encoding proteins involved in degradation of aromatic compounds. We identified 66 Tct and nine TRAP-T systems and a complete tricarboxylic acid cycle, which may allow CNB-2 to take up and metabolize a range of carboxylic acids. This nutritional bias for carboxylic acids and aromatic compounds enables strain CNB-2 to occupy unique niches in environments. Four different sets of terminal oxidases for the respiratory system were identified, and they putatively functioned at different oxygen concentrations. This study conclusively revealed at the genomic level that the genetic versatility of C. testosteroni is vital for competition with other bacteria in its special niches.The members of the genus Comamonas are gram-negative, strict aerobes and frequently occur in diverse habitats, including activated sludge, marshes, marine habitats, and plant and animal tissues (4, 12, 13). They grow on organic acids, amino acids, and peptone, but they rarely attack carbohydrates. Some species, such as Comamonas testosteroni, can also mineralize complex and xenobiotic compounds, such as testosterone (17) and 4-chloronitrobenzene (CNB) (54). Their diversified niches make Comamonas species environmentally important and also suggest that the genus Comamonas represents a group of bacteria that can adapt very well, both ecologically and physiologically, to environments.To understand better how environmental microbes adapt to their environments, many well-known environmental microbes, such as Pseudomonas putida (53) and Rhodococcus sp. strain RAH1 (31), have been sequenced. The genome data for these organisms, as well as other environmental microbes, provide not only an understanding of physiological and environmental functions at the genetic level but also a starting point for systems biology analyses of these microbes. Until now, none of the Comamonas species has been sequenced, although these organisms represent an important group of environmental microbes.C. testosteroni strain CNB-1 was isolated from CNB-contaminated activated sludge and grows with CNB as a sole source of carbon and nitrogen, and it has been used successfully for rhizoremediation of CNB-polluted soil (25). Strain CNB-1 has a circular chromosome and a large plasmid, and the genes involved in the degradation of CNB on plasmid pCNB1 were identified previously (28). In the present study, the genome of strain CNB-2, which was derived from strain CNB-1, was sequenced, and a genome analysis was performed parallel to physiological experiments. The aim of this work was to obtain genetic insight into how C. testosteroni adapts to changing and diverse environments.     

Adaptation of the Avian Egg to High Altitude

Theoretical predictions and experiments on eggs of domesticatedbirds indicate that the diffusion coefficient of gases is inverselyproportional to barometric pressure. Therefore potentially lethallosses of CO₂ and water vapor from eggs laid at high altitudemight result if the increased tendency of gases to diffuse atreduced barometric pressure were not counteracted in some manner.Limited data from two wild populations indicate that water lossfrom eggs is independent of altitude over a 3000 m elevationalgradient. Four different possibilities are discussed by whichcompensation for increased diffusion of water vapor might beachieved at high elevations 1) a reduction in eggshell conductance(GH₂O) 2) an increase in the initial water content of the eggs3) an increase in shell thickness, and 4) alteration of watervapor pressure in the nest microenvironment or incubation temperatureby variation in parental behavior. Mean GH₂O of eggs of twoprecocial and four altricial species breeding above 2800 m issignificantly reduced below values of related birds breedingat lower elevations, but no change in initial water contentor shell thickness has been observed in such eggs. Observationsof parental behavior in species breeding over wide elevationalgradients have not yet been made. Identification of the mechanismsby which eggshell structure is modified to achieve a reducedGH₂O the environmental cues used by females to determine theelevation of the breeding location and the rapidity with whichshell structuie can be modified awaits further research.     

The Molecular Genetic Architecture of Self-Employment

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable–entrepreneurship–that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ_g²/σ_P² = 25%, h² = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10⁻⁵ were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.     

Change of Genetic Architecture in Response to Sex

A traditional view is that sexual reproduction increases the potential for phenotypic evolution by expanding the range of genetic variation upon which natural selection can act. However, when nonadditive genetic effects and genetic disequilibria underlie a genetic system, genetic slippage (a change in the mean genotypic value contrary to that promoted by selection) in response to sex may occur. Additionally, depending on whether natural selection is predominantly stabilizing or disruptive, recombination may either enhance or reduce the level of expressed genetic variance. Thus, the role of sexual reproduction in the dynamics of phenotypic evolution depends heavily upon the nature of natural selection and the genetic system of the study population. In the present study, on a permanent lake Daphnia pulicaria population, sexual reproduction resulted in significant genetic slippage and a significant increase in expressed genetic variance for several traits. These observations provide evidence for substantial genetic disequilibria and nonadditive genetic effects underlying the genetic system of the study population. From these results, the fitness function of the previous clonal selection phase is inferred to be directional and/or stabilizing. The data are also used to infer the effects of natural selection on the mean and the genetic variance of the population.     

High Altitude Adaptation in Mammals

The physiological, morphological, and biochemical characteristicsof several species of mammals resident at high altitude arecompared with those of their sea level counterparts. The differencesnoted in these characteristics are in a direction that facilitatesthe acclimatization of those living at high altitude. The differencesamong species point to the fact that the mechanism of adaptationto altitude (i.e., hypoxia) is still not understood. This reviewemphasizes that the adaptive process is complex and made upof several components, that these components are inter-related,and that neither the physiological nor morphological adaptationscan fully account for the tolerance to hypoxia. Although onlysuperficially studied as yet, the biochemical adaptations appearmost important.     

The Genetic Architecture of Maize Stalk Strength

Stalk strength is an important trait in maize (Zea mays L.). Strong stalks reduce lodging and maximize harvestable yield. Studies show rind penetrometer resistance (RPR), or the force required to pierce a stalk rind with a spike, is a valid approximation of strength. We measured RPR across 4,692 recombinant inbreds (RILs) comprising the maize nested association mapping (NAM) panel derived from crosses of diverse inbreds to the inbred, B73. An intermated B73×Mo17 family (IBM) of 196 RILs and a panel of 2,453 diverse inbreds from the North Central Regional Plant Introduction Station (NCRPIS) were also evaluated. We measured RPR in three environments. Family-nested QTL were identified by joint-linkage mapping in the NAM panel. We also performed a genome-wide association study (GWAS) and genomic best linear unbiased prediction (GBLUP) in each panel. Broad sense heritability computed on a line means basis was low for RPR. Only 8 of 26 families had a heritability above 0.20. The NCRPIS diversity panel had a heritability of 0.54. Across NAM and IBM families, 18 family-nested QTL and 141 significant GWAS associations were identified for RPR. Numerous weak associations were also found in the NCRPIS diversity panel. However, few were linked to loci involved in phenylpropanoid and cellulose synthesis or vegetative phase transition. Using an identity-by-state (IBS) relationship matrix estimated from 1.6 million single nucleotide polymorphisms (SNPs) and RPR measures from 20% of the NAM panel, genomic prediction by GBLUP explained 64±2% of variation in the remaining RILs. In the NCRPIS diversity panel, an IBS matrix estimated from 681,257 SNPs and RPR measures from 20% of the panel explained 33±3% of variation in the remaining inbreds. These results indicate the high genetic complexity of stalk strength and the potential for genomic prediction to hasten its improvement.     

地山雀血红蛋白高原低氧适应的分子机制

血红蛋白(hemoglobin,Hb)作为血液循环系统中氧气运输的主要载体,在动物高原低氧适应中发挥关键作用.本文结合基因组、转录物组、分子进化、同源建模和分子动力学计算等分析,探索了高原土著鸟类地山雀血氧亲和力升高的分子机制.结果表明,与大山雀相比(RPKM为0),胚胎特异表达ρ基因在地山雀成体肝中表达较高(RPKM...     

Widespread Signals of Convergent Adaptation to High Altitude in Asia and America

Living at high altitude is one of the most difficult challenges that humans had to cope with during their evolution. Whereas several genomic studies have revealed some of the genetic bases of adaptations in Tibetan, Andean, and Ethiopian populations, relatively little evidence of convergent evolution to altitude in different continents has accumulated. This lack of evidence can be due to truly different evolutionary responses, but it can also be due to the low power of former studies that have mainly focused on populations from a single geographical region or performed separate analyses on multiple pairs of populations to avoid problems linked to shared histories between some populations. We introduce here a hierarchical Bayesian method to detect local adaptation that can deal with complex demographic histories. Our method can identify selection occurring at different scales, as well as convergent adaptation in different regions. We apply our approach to the analysis of a large SNP data set from low- and high-altitude human populations from America and Asia. The simultaneous analysis of these two geographic areas allows us to identify several candidate genome regions for altitudinal selection, and we show that convergent evolution among continents has been quite common. In addition to identifying several genes and biological processes involved in high-altitude adaptation, we identify two specific biological pathways that could have evolved in both continents to counter toxic effects induced by hypoxia.     

The Photosynthetic Response to Elevated CO2 in High Altitude Potato Species (Solanum curtilobum)

Plants of Solanum curtilobum (from high altitude) and Solanum tuberosum (from low altitude) were grown in open-top chambers in a greenhouse at either ambient (AC, 360 µmol mol^–1) or ca. twice ambient (EC, 720 µmol mol^–1) CO₂ concentrations for 30 d. CO₂ treatments started at the reproductive stage of the plants. There were similar patterns in the physiological response to CO₂ enrichment in the two species. Stomatal conductance was reduced by 59 % in S. tuberosum and by 55 % in S. curtilobum, but such a reduction did not limit the net photosynthetic rate (P _N), which was increased by approximately 56 % in S. curtilobum and 53 % in S. tuberosum. The transpiration rate was reduced by 16 % in both potato species while instantaneous transpiration efficiency increased by 80 % in S. tuberosum and 90 % in S. curtilobum. Plants grown under EC showed 36 and 66 % increment in total dry biomass, whereas yields (dry mass of tubers) were increased by 40 and 85 % in S. tuberosum and S. curtilobum, respectively. EC promoted productivity by increasing P _N. Thus S. tuberosum, cultivated around the world at low altitudes, and S. curtilobum, endemic of the highland Andes, respond positively to EC during the tuberisation stage.     

Adaptation of the Long-Lived Monocarpic Perennial Saxifraga longifolia to High Altitude

Global change is exerting a major effect on plant communities, altering their potential capacity for adaptation. Here, we aimed at unveiling mechanisms of adaptation to high altitude in an endemic long-lived monocarpic, Saxifraga longifolia, by combining demographic and physiological approaches. Plants from three altitudes (570, 1100, and 2100 m above sea level [a.s.l.]) were investigated in terms of leaf water and pigment contents, and activation of stress defense mechanisms. The influence of plant size on physiological performance and mortality was also investigated. Levels of photoprotective molecules (α-tocopherol, carotenoids, and anthocyanins) increased in response to high altitude (1100 relative to 570 m a.s.l.), which was paralleled by reduced soil and leaf water contents and increased ABA levels. The more demanding effect of high altitude on photoprotection was, however, partly abolished at very high altitudes (2100 m a.s.l.) due to improved soil water contents, with the exception of α-tocopherol accumulation. α-Tocopherol levels increased progressively at increasing altitudes, which paralleled with reductions in lipid peroxidation, thus suggesting plants from the highest altitude effectively withstood high light stress. Furthermore, mortality of juveniles was highest at the intermediate population, suggesting that drought stress was the main environmental driver of mortality of juveniles in this rocky plant species. Population structure and vital rates in the high population evidenced lower recruitment and mortality in juveniles, activation of clonal growth, and absence of plant size-dependent mortality. We conclude that, despite S. longifolia has evolved complex mechanisms of adaptation to altitude at the cellular, whole-plant and population levels, drought events may drive increased mortality in the framework of global change.European mountains shelter a huge biodiversity and are home to many endemic plants and animals, i.e. species that occur nowhere else. Global change, and particularly climatic change, is expected to exert a major effect on mountain plant communities, altering their potential capacity for adaptation (Peñuelas and Boada, 2003; Franklin et al., 2016). Under such a scenario of environmental change, populations of organisms must either escape or get quickly adapted, otherwise they go extinct. For instance, certain butterfly species have been migrating north, or to higher altitudes, to escape rising temperatures (Breed et al., 2013). Plants, of course, cannot migrate as fast as animals, and important shifts have already been found among plant communities inhabiting mountain summits (Gottfried et al., 2012). When global air temperatures increase, the number of cooler habitats will shrink, producing a crowding effect and increased competition among some species in the remaining cooler areas; at the same time, however, other habitat types will increase in abundance (Scherrer and Körner, 2011). Alpine habitats could prove more attractive to plant species than lowlands because of their topography providing favorable microhabitats. However, certain rare species may lose out in the long-term competition for space, especially those favoring cooler climates (Körner, 2013).Leaves of high-mountain plants are highly resistant to photoinhibitory damage. Tocochromanols (particularly tocopherols and plastochromanol-8) are found in thylakoids and play an antioxidant function in protecting lipids from the propagation of lipid peroxidation in chloroplasts. Together with carotenoids, they also prevent PSII damage as a result of singlet oxygen attack (Munné-Bosch and Alegre, 2002; Falk and Munné-Bosch, 2010; Zbierzak et al., 2009; Kruk et al., 2014). A higher tocochromanol content, particularly of α-tocopherol, and an increased capacity for nonradiative dissipation of excitation energy by activation of the xanthophyll cycle have been found in high-mountain plants, thus supporting such a role (Streb et al., 1997, 1998, 2003a, 2003b; García-Plazaola et al., 2015). Furthermore, although the number of studies is still very limited for plants in their natural habitat, high-mountain plants tend to accumulate large amounts of ABA (Bano et al., 2009), a phytohormone that is known to mediate the acclimation/adaptation of plants to temperature extremes by modulating the up- and down-regulation of numerous genes (Gilmour and Thomashow, 1991). The activation of other chemical defenses, such as the accumulation of salicylates and jasmonates, which serve against biotrophs and necrotrophs, can also be affected by extreme temperatures (Kosova et al., 2012; Dong et al., 2014; Miura and Tada, 2014), but it has not been investigated thus far in high-mountain plants.Some degree of plasticity in physiological traits is ubiquitous among plants so that environmental growth conditions are generally considered essential factors governing the physiological performance of plants and their organs (Larcher, 1994). A number of recent studies with trees, shrubs, and herbs, including vascular epiphytes (Mencuccini and Grace 1996; Zotz, 1997; Schmidt et al., 2001; Schmidt and Zotz, 2001; Munné-Bosch and Lalueza, 2007; Morales et al., 2014), point out, however, to another source of intraspecific variation that many studies in the past have inadvertently missed, i.e. substantial variation in physiological traits related to plant size rather than changing environmental conditions (Zotz et al., 2001). In trees, increased plant size leads to increased hydraulic resistance causing reductions in relative leaf growth rates (Mencuccini and Grace, 1996). Furthermore, photo-oxidative stress has been shown to increase during periods of low precipitation combined with high light in the Mediterranean shrub Cistus clusii as a function of plant size, therefore suggesting an increased vulnerability to photo-oxidative stress in the largest individuals (Munné-Bosch and Lalueza, 2007). To our knowledge, no studies are however available to unveil the possible influence of plant size on photoprotection and activation of chemical defenses in high-mountain plants.Saxifraga longifolia Lapeyruse (Saxiragaceae) is an endemic species of the western Mediterranean mountains, ranging from the Pyrenees (plus a couple of populations in the Cantabric Mountains) through eastern Spain to reach its southern limit in the high Atlas of Morocco (Webb and Gornall, 1989). This long-lived monocarpic plant develops a basal rosette growing in limestone rocky places, mainly on cliffs, offering a unique sight in years of intensive blooming. Reproduction occurs when plants are at least 6 years old in greenhouse conditions (Webb and Gornall, 1989), and it is thought to be much later in natural conditions. This orophyte plant shows striking variation in plant size, with a diameter of the rosette up to 30 cm in the largest individuals. It has been shown that flower and seed production increase as a function of plant size, with female success being maximum in intermediate sized plants (García, 2003).In the current study, with the aim of getting new insights into the mechanisms of adaptation to high altitudes and the influence of plant size on this adaptation capacity, we examined the physiological response of S. longifolia growing at three contrasted populations spanning its whole altitudinal range. We described population structure, calculated mortality rates, and analyzed physiological performance, including water contents and activation of photoprotection mechanisms and chemical defenses. We aimed at understanding the effect of varying altitude on the expression of defense mechanisms that govern adaptive processes in high-mountain plants.