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Footprints of natural selection at the mannose-6-phosphate isomerase locus in barnacles.

ABSTRACT: The mannose-6-phosphate isomerase (Mpi) locus in Semibalanus balanoides has been studied as a candidate gene for balancing selection for more than two decades. Previous work has shown that Mpi allozyme genotypes (fast and slow) have different frequencies across Atlantic intertidal zones due to selection on postsettlement survival (i.e., allele zonation). We present the complete gene sequence of the Mpi locus and quantify nucleotide polymorphism in S. balanoides, as well as divergence to its sister taxon Semibalanus cariosus We show that the slow allozyme contains a derived charge-altering amino acid polymorphism, and both allozyme classes correspond to two haplogroups with multiple internal haplotypes. The locus shows several footprints of balancing selection around the fast/slow site: an enrichment of positive Tajima's D for nonsynonymous mutations, an excess of polymorphism, and a spike in the levels of silent polymorphism relative to silent divergence, as well as a site frequency spectrum enriched for midfrequency mutations. We observe other departures from neutrality across the locus in both coding and noncoding regions. These include a nonsynonymous trans-species polymorphism and a recent mutation under selection within the fast haplogroup. The latter suggests ongoing allelic replacement of functionally relevant amino acid variants. Moreover, predicted models of Mpi protein structure provide insight into the functional significance of the putatively selected amino acid polymorphisms. While footprints of selection are widespread across the range of S. balanoides, our data show that intertidal zonation patterns are variable across both spatial and temporal scales. These data provide further evidence for heterogeneous selection on Mpi.

SUBMITTER: Nunez JCB

PROVIDER: S-EPMC7071928 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Footprints of natural selection at the mannose-6-phosphate isomerase locus in barnacles.

Nunez Joaquin C B JCB Flight Patrick A PA Neil Kimberly B KB Rong Stephen S Eriksson Leif A LA Ferranti David A DA Rosenblad Magnus Alm MA Blomberg Anders A Rand David M DM

Proceedings of the National Academy of Sciences of the United States of America 20200225 10

The mannose-6-phosphate isomerase (Mpi) locus in Semibalanus balanoides has been studied as a candidate gene for balancing selection for more than two decades. Previous work has shown that Mpi allozyme genotypes (fast and slow) have different frequencies across Atlantic intertidal zones due to selection on postsettlement survival (i.e., allele zonation). We present the complete gene sequence of the Mpi locus and quantify nucleotide polymorphism in S. balanoides ...[more]

PMID: 32098846

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Project description:BackgroundMannose, a natural hexose existing in daily food, has been demonstrated to preferentially inhibit the progression of tumors with low expression of phosphate mannose isomerase (PMI). However, its function in thyroid cancer still remains elusive.MethodsMTT, colony formation and flow cytometry assays were performed to determine the response of thyroid cancer cells to mannose. Meanwhile, mouse models of subcutaneous xenograft and primary papillary thyroid cancer were established to determine in vivo anti-tumor activity of mannose. The underlying mechanism of mannose selectively killing thyroid cancer cells was clarified by a series of molecular and biochemical experiments.ResultsOur data demonstrated that mannose selectively suppressed the growth of thyroid cancer cells, and found that enzyme activity of PMI rather than its protein expression was negatively associated with the response of thyroid cancer cells to mannose. Besides, our data showed that zinc ion (Zn2+) chelator TPEN clearly increased the response of mannose-insensitive cells to mannose by inhibiting enzyme activity of PMI, while Zn2+ supplement could effectively reverse this effect. Further studies found that the expression of zinc transport protein ZIP10, which transport Zn2+ from extracellular area into cells, was negatively related to the response of thyroid cancer cells to mannose. Knocking down ZIP10 in mannose-insensitive cells significantly inhibited in vitro and in vivo growth of these cells by decreasing intracellular Zn2+ concentration and enzyme activity of PMI. Moreover, ectopic expression of ZIP10 in mannose-sensitive cells decrease their cellular response to mannose. Mechanistically, mannose exerted its anti-tumor effect by inhibiting cellular glycolysis; however, this effect was highly dependent on expression status of ZIP10.ConclusionThe present study demonstrate that mannose selectively kills thyroid cancer cells dependent on enzyme activity of PMI rather than its expression, and provide a mechanistic rationale for exploring clinical use of mannose in thyroid cancer therapy.

Project description:Natural selection is likely a major factor in shaping genomic variation of the African indigenous rural chicken, driving the development of genetic footprints. Selection footprints are expected to be associated with adaptation to locally prevailing environmental stressors, which may include diverse factors as high altitude, disease resistance, poor nutrition, oxidative and heat stresses. To determine the existence of a selection footprint, 268 birds were randomly sampled from three indigenous ecotypes from East Africa (Rwanda and Uganda) and North Africa (Baladi), and two registered Egyptian breeds (Dandarawi and Fayoumi). Samples were genotyped using the chicken Affymetrix 600K Axiom® Array. A total of 494,332 SNPs were utilized in the downstream analysis after implementing quality control measures. The intra-population runs of homozygosity (ROH) that occurred in >50% of individuals of an ecotype or in >75% of a breed were studied. To identify inter-population differentiation due to genetic structure, FST was calculated for North- vs. East-African populations and Baladi and Fayoumi vs. Dandarawi for overlapping windows (500 kb with a step-size of 250 kb). The ROH and FST mapping detected several selective sweeps on different autosomes. Results reflected selection footprints of the environmental stresses, breed behavior, and management. Intra-population ROH of the Egyptian chickens showed selection footprints bearing genes for adaptation to heat, solar radiation, ion transport and immunity. The high-altitude-adapted East-African populations' ROH showed a selection signature with genes for angiogenesis, oxygen-heme binding and transport. The neuroglobin gene (GO:0019825 and GO:0015671) was detected on a Chromosome 5 ROH of Rwanda-Uganda ecotypes. The sodium-dependent noradrenaline transporter, SLC6A2 on a Chromosome 11 ROH in Fayoumi breed may reflect its active behavior. Inter-population FST among Egyptian populations reflected genetic mechanisms for the Fayoumi resistance to Newcastle Disease Virus (NDV), while FST between Egyptian and Rwanda-Uganda populations indicated the Secreted frizzled related protein 2, SFRP2, (GO:0009314) on Chromosome 4, that contributes to melanogenic activity and most likely enhances the Dandarawi chicken adaptation to high-intensity of solar radiation in Southern Egypt. These results enhance our understanding of the natural selection forces role in shaping genomic structure for adaptation to the stressful African conditions.

Dataset Information

Footprints of natural selection at the mannose-6-phosphate isomerase locus in barnacles.

Publications

Footprints of natural selection at the mannose-6-phosphate isomerase locus in barnacles.

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