Most plants are polyploid due to whole-genome duplications （WGD） and can thus have duplicated genes. Following a WGD, paralogs are often fractionated （lost） and few duplicate pairs remain. Little attention has bee...Most plants are polyploid due to whole-genome duplications （WGD） and can thus have duplicated genes. Following a WGD, paralogs are often fractionated （lost） and few duplicate pairs remain. Little attention has been paid to the role of DNA methylation in the functional divergence of paralogous genes. Using high- resolution methylation maps of accessions of domesticated and wild soybean, we show that in soybean, a recent paleopolyploid with many paralogs, DNA methylation likely contributed to the elimination of ge- netic redundancy of polyploidy-derived gene paralogs. Transcriptionally silenced paralogs exhibit partic- ular genomic features as they are often associated with proximal transposable elements （TEs） and are pref- erentially located in pericentromeres, likely due to gene movement during evolution. Additionally, we provide evidence that gene methylation associated with proximal TEs is implicated in the divergence of expression profiles between orthologous genes of wild and domesticated soybean, and within populations.展开更多
The historical relationships of nine areas of endemism of the tropical montane cloud forests(TMCFs)were analysed based on a temporal cladistic biogeographical approach.Three cladistic biogeographical analyses were con...The historical relationships of nine areas of endemism of the tropical montane cloud forests(TMCFs)were analysed based on a temporal cladistic biogeographical approach.Three cladistic biogeographical analyses were conducted based on 29cladograms of terrestrial taxa by partitioning them into three time-slices,namely,Miocene,Pliocene,and Pleistocene.The results showed different area relationships over time.For the Miocene and Pliocene time slices,the Isthmus of Tehuantepec acted as a geographic barrier that fragmented the TMCFs into two portions:west of the Isthmus and east of the Isthmus.In the case of the Pleistocene,the TMCFs were broken into two portions,one related to the Neotropical region and the other to the Nearctic region.Furthermore,the analyses allowed us to detect the influences of different geological and paleoclimatological events on the distribution of the TMCFs over time.Therefore,the TMCFs current distribution might have been driven by geological events during the Miocene-Pliocene,whereas climatic fluctuations have the highest impact during the Pleistocene.展开更多
Spinal muscular atrophy(SMA)is caused by dysfunction of the alpha motor neurons of the spinal cord.It is an autosomal recessive disease associated to the SMN1 gene,located in the subtelomeric region of 5q13.A paralog ...Spinal muscular atrophy(SMA)is caused by dysfunction of the alpha motor neurons of the spinal cord.It is an autosomal recessive disease associated to the SMN1 gene,located in the subtelomeric region of 5q13.A paralog SMN2 gene is located at the centromeric region of the same chromosome,which apparently originated by an ancestral inverted duplication occurring only in humans.The exon sequence differs in two nucleotides in exon 7 and exon 8,which leads to an SMN2 transcript that lacks exon 7 and results in a truncated protein.Part(10%)of the SMN2 transcripts avoids the splicing of exon 7 but most of the copies are dysfunctional.In a disease scenario,the more SMN2 copies the higher possibility to restore at least partly the effects of SMN1 deficiency.Some therapeutic approaches are being developed to increase the expression of SMN2.To determine the number of SMN1 and SMN2 copies,the methodology must distinguish accurately between both genes.In this work,we present the results obtained using multiplex ligation-dependent probe amplification(MLPA)in 60 SMA suspected patients/carriers derived from different regions of Argentina.In 32 of these DNA samples we found alterations in SMN1.Among these,16 presented a heterozygous deletion(carrier status)and 14 an homozygous deletion(patient status)in exon 7 and 8 of SMN1.In one case,exon 7 was found homozygously deleted but exon 8 presented a single copy,and in another case,exon 7 was found heterozygously deleted while exon 8 was normal.Almost half of the patients(7/15)presented a normal diploid number of SMN2 while the other half(8/15)presented an increased number.In this work we showed how a probe-based methodology such as MLPA was able to distinguish between the paralog genes and determine the amount of copies in DNA samples from suspected patients/carriers of SMA.展开更多
Cereal genes are classified into two distinct classes according to the guanine-cytosine （GC） content at the third codon sites （GC3）. Natural selection and mutation bias have been proposed to affect the GC content....Cereal genes are classified into two distinct classes according to the guanine-cytosine （GC） content at the third codon sites （GC3）. Natural selection and mutation bias have been proposed to affect the GC content. However, there has been controversy about the cause of GC variation. Here, we characterized the GC content of 1 092 paralogs and other single-copy genes in the duplicated chromosomal regions of the rice genome （ssp. indica） and classified the paralogs into GC3-rich and GC3-poor groups. By referring to out-group sequences from Arabidopsis and maize, we confirmed that the average synonymous substitution rate of the GC3-rich genes is significantly lower than that of the GC3-poor genes. Furthermore, we explored the other possible factors corresponding to the GC variation including the length of coding sequences, the number of exons in each gene, the number of genes in each family, the location of genes on chromosomes and the protein functions. Consequently, we propose that natural selection rather than mutation bias was the primary cause of the GC variation.展开更多
Hox genes, responsible for regional specification along the anteroposterior axis in embryogenesis, are found as clusters in most eumetazoan genomes sequenced to date. Invertebrates possess a single Hox gene cluster wi...Hox genes, responsible for regional specification along the anteroposterior axis in embryogenesis, are found as clusters in most eumetazoan genomes sequenced to date. Invertebrates possess a single Hox gene cluster with some exceptions of secondary cluster breakages, while osteichthyans （bony vertebrates） have multiple Hox clusters. In tetrapods, four Hox clusters, derived from the so-called two-round whole genome duplications （2R-WGDs）, are observed. Overall, the number of Hox gene clusters has been regarded as a reliable marker of ploidy levels in animal genomes. In fact, this scheme also fits the situations in teleost fishes that experienced an additional WGD. In this review, I focus on cyclostomes and cartilaginous fishes as lineages that would fill the gap between invertebrates and osteichthyans. A recent study highlighted a possible loss of the HoxC cluster in the galeomorph shark lineage, while other aspects of cartilaginous fish Hox clusters usually mark their conserved nature. In contrast, existing resources suggest that the cyclostomes exhibit a different mode of Hox cluster organization. For this group of species, whose genomes could have differently responded to the 2R-WGDs from jawed vertebrates, therefore the number of Hox clusters may not serve as a good indicator of their ploidy level.展开更多
Side effects from targeted drugs remain a serious conccrn. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which arc highly homologous in sequences and have similar struct...Side effects from targeted drugs remain a serious conccrn. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which arc highly homologous in sequences and have similar structures and drug-binding pockets. To identify targctablc differences between paralogs, we analyzed two types （type-I and type-ll） of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors （GPCRs） at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor （GCGR） and glucagon-like peptide-I receptor （GLP-I R）, exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes. Our data showed that type-ll alnino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR. which had a radical shift in physicochemical properties between GCGR and GLP-1R. We also examined the role of type-I amino acids between GCGR and GLP-IR. The divergent features between GCGR and GLP-I R paralogs may be helpful in their discrimination, thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs.展开更多
文摘Most plants are polyploid due to whole-genome duplications （WGD） and can thus have duplicated genes. Following a WGD, paralogs are often fractionated （lost） and few duplicate pairs remain. Little attention has been paid to the role of DNA methylation in the functional divergence of paralogous genes. Using high- resolution methylation maps of accessions of domesticated and wild soybean, we show that in soybean, a recent paleopolyploid with many paralogs, DNA methylation likely contributed to the elimination of ge- netic redundancy of polyploidy-derived gene paralogs. Transcriptionally silenced paralogs exhibit partic- ular genomic features as they are often associated with proximal transposable elements （TEs） and are pref- erentially located in pericentromeres, likely due to gene movement during evolution. Additionally, we provide evidence that gene methylation associated with proximal TEs is implicated in the divergence of expression profiles between orthologous genes of wild and domesticated soybean, and within populations.
基金the CONACyT 478077partially financed by DGAPA-PAPIIT 220621。
文摘The historical relationships of nine areas of endemism of the tropical montane cloud forests(TMCFs)were analysed based on a temporal cladistic biogeographical approach.Three cladistic biogeographical analyses were conducted based on 29cladograms of terrestrial taxa by partitioning them into three time-slices,namely,Miocene,Pliocene,and Pleistocene.The results showed different area relationships over time.For the Miocene and Pliocene time slices,the Isthmus of Tehuantepec acted as a geographic barrier that fragmented the TMCFs into two portions:west of the Isthmus and east of the Isthmus.In the case of the Pleistocene,the TMCFs were broken into two portions,one related to the Neotropical region and the other to the Nearctic region.Furthermore,the analyses allowed us to detect the influences of different geological and paleoclimatological events on the distribution of the TMCFs over time.Therefore,the TMCFs current distribution might have been driven by geological events during the Miocene-Pliocene,whereas climatic fluctuations have the highest impact during the Pleistocene.
文摘Spinal muscular atrophy(SMA)is caused by dysfunction of the alpha motor neurons of the spinal cord.It is an autosomal recessive disease associated to the SMN1 gene,located in the subtelomeric region of 5q13.A paralog SMN2 gene is located at the centromeric region of the same chromosome,which apparently originated by an ancestral inverted duplication occurring only in humans.The exon sequence differs in two nucleotides in exon 7 and exon 8,which leads to an SMN2 transcript that lacks exon 7 and results in a truncated protein.Part(10%)of the SMN2 transcripts avoids the splicing of exon 7 but most of the copies are dysfunctional.In a disease scenario,the more SMN2 copies the higher possibility to restore at least partly the effects of SMN1 deficiency.Some therapeutic approaches are being developed to increase the expression of SMN2.To determine the number of SMN1 and SMN2 copies,the methodology must distinguish accurately between both genes.In this work,we present the results obtained using multiplex ligation-dependent probe amplification(MLPA)in 60 SMA suspected patients/carriers derived from different regions of Argentina.In 32 of these DNA samples we found alterations in SMN1.Among these,16 presented a heterozygous deletion(carrier status)and 14 an homozygous deletion(patient status)in exon 7 and 8 of SMN1.In one case,exon 7 was found homozygously deleted but exon 8 presented a single copy,and in another case,exon 7 was found heterozygously deleted while exon 8 was normal.Almost half of the patients(7/15)presented a normal diploid number of SMN2 while the other half(8/15)presented an increased number.In this work we showed how a probe-based methodology such as MLPA was able to distinguish between the paralog genes and determine the amount of copies in DNA samples from suspected patients/carriers of SMA.
基金the State Key Basic Research and Development Plan of China(2003CB715900)the National Natural Science Foundation of China(90408015,30121003 and 30430030).
文摘Cereal genes are classified into two distinct classes according to the guanine-cytosine （GC） content at the third codon sites （GC3）. Natural selection and mutation bias have been proposed to affect the GC content. However, there has been controversy about the cause of GC variation. Here, we characterized the GC content of 1 092 paralogs and other single-copy genes in the duplicated chromosomal regions of the rice genome （ssp. indica） and classified the paralogs into GC3-rich and GC3-poor groups. By referring to out-group sequences from Arabidopsis and maize, we confirmed that the average synonymous substitution rate of the GC3-rich genes is significantly lower than that of the GC3-poor genes. Furthermore, we explored the other possible factors corresponding to the GC variation including the length of coding sequences, the number of exons in each gene, the number of genes in each family, the location of genes on chromosomes and the protein functions. Consequently, we propose that natural selection rather than mutation bias was the primary cause of the GC variation.
基金supported by the Young Scholar Fund from University of Konstanz and grants from German Research Foundation(KU2669/1-1)
文摘Hox genes, responsible for regional specification along the anteroposterior axis in embryogenesis, are found as clusters in most eumetazoan genomes sequenced to date. Invertebrates possess a single Hox gene cluster with some exceptions of secondary cluster breakages, while osteichthyans （bony vertebrates） have multiple Hox clusters. In tetrapods, four Hox clusters, derived from the so-called two-round whole genome duplications （2R-WGDs）, are observed. Overall, the number of Hox gene clusters has been regarded as a reliable marker of ploidy levels in animal genomes. In fact, this scheme also fits the situations in teleost fishes that experienced an additional WGD. In this review, I focus on cyclostomes and cartilaginous fishes as lineages that would fill the gap between invertebrates and osteichthyans. A recent study highlighted a possible loss of the HoxC cluster in the galeomorph shark lineage, while other aspects of cartilaginous fish Hox clusters usually mark their conserved nature. In contrast, existing resources suggest that the cyclostomes exhibit a different mode of Hox cluster organization. For this group of species, whose genomes could have differently responded to the 2R-WGDs from jawed vertebrates, therefore the number of Hox clusters may not serve as a good indicator of their ploidy level.
基金supported by a grant from the National Natural Science Foundation of China(Grant No.31571355 and 31301034)supported by Fudan University,ChinaIowa State University,United States
文摘Side effects from targeted drugs remain a serious conccrn. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which arc highly homologous in sequences and have similar structures and drug-binding pockets. To identify targctablc differences between paralogs, we analyzed two types （type-I and type-ll） of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors （GPCRs） at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor （GCGR） and glucagon-like peptide-I receptor （GLP-I R）, exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes. Our data showed that type-ll alnino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR. which had a radical shift in physicochemical properties between GCGR and GLP-1R. We also examined the role of type-I amino acids between GCGR and GLP-IR. The divergent features between GCGR and GLP-I R paralogs may be helpful in their discrimination, thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs.
