Serotonin (5-hydroxytryptamine) is a neurotransmitter crucial for cardiovascular, gastrointestinal, and brain function. It is also involved in several aspects of behavior and associated with a ...variety of personality disorders in humans. Its dual role as a crucial element in vital physiological functions (strictly evolutionary conserved) and in traits that differ substantially across species makes the evolution of serotonin function particularly interesting. We studied the evolution of serotonin function through the identification of the selective forces shaping the evolution of genes in its functional pathway in primates and rodents. Serotonin genes are highly conserved and show no signals of positive selection, suggesting functional constraint as the main force driving their evolution. They show, nevertheless, considerable differences in constraint between primates and rodents, with some genes showing dramatic differences between the 2 groups. These genes most likely represent cases of functional divergence between primates and rodents and point out to the relevance of using closely related species in gene-based evolutionary studies to avoid the effect of unrecognized functional differences between distant species. Within each group (rodents or primates), genes also show heterogeneity in evolution. Genes from the same gene family (with structure and function alike) tend to evolve at a similar rate, but this is not always the case. A few serotonin genes show substantial differences in constraint with the rest of members of their family, suggesting the presence of important and unrecognized functional differences among the genes, which may be involved in species-specific evolution.
The genus Pan is the closest genus to our own and it includes two species, Pan paniscus (bonobos) and Pan troglodytes (chimpanzees). The later is constituted by four subspecies, all highly ...endangered. The study of the Pan genera has been incessantly complicated by the intricate relationship among subspecies and the statistical limitations imposed by the reduced number of samples or genomic markers analyzed. Here, we present a new method to reconstruct complete mitochondrial genomes (mitogenomes) from whole genome shotgun (WGS) datasets, mtArchitect, showing that its reconstructions are highly accurate and consistent with long-range PCR mitogenomes. We used this approach to build the mitochondrial genomes of 20 newly sequenced samples which, together with available genomes, allowed us to analyze the hitherto most complete Pan mitochondrial genome dataset including 156 chimpanzee and 44 bonobo individuals, with a proportional contribution from all chimpanzee subspecies. We estimated the separation time between chimpanzees and bonobos around 1.15 million years ago (Mya) 0.81-1.49. Further, we found that under the most probable genealogical model the two clades of chimpanzees, Western + Nigeria-Cameroon and Central + Eastern, separated at 0.59 Mya 0.41-0.78 with further internal separations at 0.32 Mya 0.22-0.43 and 0.16 Mya 0.17-0.34, respectively. Finally, for a subset of our samples, we compared nuclear versus mitochondrial genomes and we found that chimpanzee subspecies have different patterns of nuclear and mitochondrial diversity, which could be a result of either processes affecting the mitochondrial genome, such as hitchhiking or background selection, or a result of population dynamics.
Aromas and flavours can be produced from fungi by either de novo synthesis or biotransformation processes. Herein, the biocatalytic potential of seven basidiomycete species from Colombia fungal ...strains isolated as endophytes or basidioma was evaluated.
,
, and
were the most potent strains capable of decolourizing β,β-carotene as evidence of their potential as biocatalysts for de novo aroma synthesis. Since a species' biocatalytic potential cannot solely be determined via qualitative screening using β,β-carotene biotransformation processes, we focused on using α-pinene biotransformation with mycelium as a measure of catalytic potential. Here, two strains of
-namely, the endophytic (ET-06) and basidioma (EBB-046) strains-were screened. Herein,
is reported for the first time as a novel biocatalyst for the oxidation of α-pinene, with a product yield of 2.9 mg of
-Verbenol per gram of dry weight mycelia used. The EBB-046 strain generated flavour compounds via the biotransformation of a Cape gooseberry medium and de novo synthesis in submerged cultures. Three aroma-producing compounds were identified via GC-MS-namely, methyl-3-methoxy-4H-pyran-4-one, hexahydro-3-(methylpropyl)-pyrrolo1,2-apyrazine-1,4-dione, and hexahydro-3-(methylphenyl)-pyrrolo1,2-apyrazine-1,4-dione.
Interferon lambda 4 gene (IFNL4) encodes IFN-λ4, a new member of the IFN-λ family with antiviral activity. In humans IFNL4 open reading frame is truncated by a polymorphic frame-shift insertion that ...eliminates IFN-λ4 and turns IFNL4 into a polymorphic pseudogene. Functional IFN-λ4 has antiviral activity but the elimination of IFN-λ4 through pseudogenization is strongly associated with improved clearance of hepatitis C virus (HCV) infection. We show that functional IFN-λ4 is conserved and evolutionarily constrained in mammals and thus functionally relevant. However, the pseudogene has reached moderately high frequency in Africa, America, and Europe, and near fixation in East Asia. In fact, the pseudogenizing variant is among the 0.8% most differentiated SNPs between Africa and East Asia genome-wide. Its raise in frequency is associated with additional evidence of positive selection, which is strongest in East Asia, where this variant falls in the 0.5% tail of SNPs with strongest signatures of recent positive selection genome-wide. Using a new Approximate Bayesian Computation (ABC) approach we infer that the pseudogenizing allele appeared just before the out-of-Africa migration and was immediately targeted by moderate positive selection; selection subsequently strengthened in European and Asian populations resulting in the high frequency observed today. This provides evidence for a changing adaptive process that, by favoring IFN-λ4 inactivation, has shaped present-day phenotypic diversity and susceptibility to disease.
Ample evidence has accumulated showing that different coding variants of the PRNP gene confer differential susceptibility for prion diseases. Here we evaluate the patterns of nucleotide variation in ...PRNP exon 2, which includes all the protein-coding sequence, by resequencing a worldwide sample of 174 humans for 2378 bp. In line with previous studies, we found two main haplotypes differentiated by nonsynonymous substitution in codon 129. Our analyses reveal the worldwide pattern of variation at the PRNP gene to be inconsistent with neutral expectations, indicating instead an excess of low-frequency variants, a footprint of the action of either positive or purifying selection. A comparison of neutrality test statistics for PRNP with other human genes indicates that the signal of positive selection on PRNP is stronger than expected from a possible confounding genome-wide background signal of population expansion. Two main conclusions arise from our analysis. First, the existence of an ancient, stable, balanced polymorphism that has been claimed in a previous study and related to cannibalism can be rejected and is shown to be due to ascertainment bias. Second, our results are consistent with a complex history of selection including mainly positive selection, even if short local periods of balancing selection (Kuru-like episodes), or even a weak purifying selection model, are consistent with our data.
Recent efforts have attempted to describe the population structure of common chimpanzee, focusing on four subspecies: Pan troglodytes verus, P. t. ellioti, P. t. troglodytes, and P. t. ...schweinfurthii. However, few studies have pursued the effects of natural selection in shaping their response to pathogens and reproduction. Whey acidic protein (WAP) four-disulfide core domain (WFDC) genes and neighboring semenogelin (SEMG) genes encode proteins with combined roles in immunity and fertility. They display a strikingly high rate of amino acid replacement (dN/dS), indicative of adaptive pressures during primate evolution. In human populations, three signals of selection at the WFDC locus were described, possibly influencing the proteolytic profile and antimicrobial activities of the male reproductive tract. To evaluate the patterns of genomic variation and selection at the WFDC locus in chimpanzees, we sequenced 17 WFDC genes and 47 autosomal pseudogenes in 68 chimpanzees (15 P. t. troglodytes, 22 P. t. verus, and 31 P. t. ellioti). We found a clear differentiation of P. t. verus and estimated the divergence of P. t. troglodytes and P. t. ellioti subspecies in 0.173 Myr; further, at the WFDC locus we identified a signature of strong selective constraints common to the three subspecies in WFDC6-a recent paralog of the epididymal protease inhibitor EPPIN. Overall, chimpanzees and humans do not display similar footprints of selection across the WFDC locus, possibly due to different selective pressures between the two species related to immune response and reproductive biology.
Monoamine oxidase A (MAOA) is the X-linked gene responsible for deamination and subsequent degradation of several neurotransmitters and other amines. Among other activities, the gene has been shown ...to play a role in locomotion, circadian rhythm, and pain sensitivity and to have a critical influence on behavior and cognition. Previous studies have reported a non-neutral evolution of the gene attributable to positive selection in the human lineage. To determine whether this selection was human-exclusive or shared with other species, we performed a population genetic analysis of the pattern of nucleotide variation in non-human species, including bonobo, chimpanzee, gorilla, and orangutan. Footprints of positive selection were absent in all analyzed species, suggesting that positive selection has been recent and unique to humans. To determine which human-unique genetic changes could have been responsible for this differential evolution, the coding region of the gene was compared between human, chimpanzee, and gorilla. Only one human exclusive non-conservative change is present in the gene: Glu151Lys. This human substitution affects protein dimerization according to a three-dimensional structural model that predicts a non-negligible functional shift. This is the only candidate position at present to have been selected to fixation in humans during an episode of positive selection. Divergence analysis among species has shown that, even under positive selection in the human lineage, the MAOA gene did not experience accelerated evolution in any of the analyzed lineages, and that tools such as K(a)/ K(s) would not have detected the selective history of the gene.
Cystic fibrosis (CF) is the most frequent severe recessive disorder in European populations. We have analyzed its mutation frequency spectrum in 94 European, North African and SW Asian populations ...taken from the literature. Most major mutations as well as the incidence of CF mutations showed clinals patterns as demonstrated by autocorrelogram analysis. More importantly, measures of mutation diversity did also show clinal patterns, with mutation spectra being more diverse in southern than in northern Europe. This increased diversity would imply roughly a three-fold long-term effective population size in southern than in northern Europe. Distances were computed among populations based on their CF mutation frequencies and compared with distances based on other genic regions. CF-based distances correlated with mtDNA but not with Y-chromosome-based distances, which may be a consequence of the relatively homogeneous CF mutation frequencies in European populations.
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