Biology subjects

Hermida, M.

Publications and source records attributed to Hermida, M..

5 recordsLinked to original sources

bioRxiv2025

Disentangling the role of chromosome inversions in the structure of flat oyster (Ostrea edulis): origin, adaptation and phylogeography

Chromosomal inversions are large-scale structural variants that disrupt recombination and contribute to population differentiation and local adaptation. In this study, we characterized the genomic features, frequency, and evolutionary significance of chromosomal inversions in the European flat oyster (Ostrea edulis), a species of ecological and commercial relevance. Using a low-density SNP array ([~]5K), we obtained confident genotyping data across the native European distribution of the species. The breakpoints of the inversions at chromosome (C) 2, C5 and C8, spanning 27, 7 and 35 Mb, respectively, were precisely mapped by combining linkage disequilibrium in a large sample and long-read sequencing. This enabled us to identify the SNPs and genes within the inversions for comparative population genomics and functional evaluation. A north to south cline was observed for the three inversions, although with low-moderate correlation between them. Strong signals for divergent selection were detected for the three inversions, although with specific profiles suggestive of adaptive peaks around highly divergent SNPs across the inversion length. The three inversions seem to be old considering genetic diversity and differentiation between arrangements. Phylogeographic events and adaptation to the current environment seem underlying the structural pattern observed. Gene content and enrichment analyses within inversions suggest that these polymorphisms may play a role in the immune system and response to different stressors including parasite resistance. Our results provide new insights into the genomic architecture of adaptation in O. edulis and highlight the potential of structural variants as targets for conservation and selective breeding.

genomics↗

bioRxiv2022

The broad shell colour variation in common cockle (Cerastoderma edule) from Northeast Atlantic relies on a major QTL revealed by GWAS using a new high-density genetic map

Shell colour pattern shows broad diversity in molluscs, and both genetic and environmental factors seem to interact to some extent on the final phenotype. Despite information on the genetic component and pathways involved in shell construction and colour has increased in the last decade, more data are needed particularly to understand colour variation and its putative role on adaptation. The European common cockle (Cerastoderma edule) is a valuable species from ecological and commercial perspectives with important variation in colour pattern, but this diversity has never been characterized and the underlying genetic architecture is unknown. In this study, we constructed a high-density genetic map, as an essential tool for genomic screening in common cockle, that was applied to ascertain the genetic basis of colour pattern variation in the species. The consensus map, including 13,874 2b-RAD SNPs, was constituted by the 19 linkage groups (LGs) corresponding to the n = 19 chromosomes of its karyotype and spanned 1,073 cM (730 markers per LG; inter-marker distance of 0.13 cM). Five full-sib families showing segregation for several colour-associated traits were used to perform a GWAS analysis. A major QTL on chromosome 13 explained most of the variation for shell colour patterns. Mining on this genomic region revealed the presence of several candidate genes enriched on Gene Ontology terms such as anatomical structure development, ion transport, membrane transport and cell periphery, closely related to shell architecture, including six chitin-related, one ependymin, several ion binding and transporters, and others related to transit across the cell membrane. Interestingly, this major QTL overlaps with a genomic region previously reported associated with divergent selection in the distribution range of the species, suggesting a putative role on local adaptation.

genomics↗

bioRxiv2022

A chromosome-level genome assembly enables the identification of the follicle stimulating hormone receptor as the master sex determining gene in Solea senegalensis

Sex determination (SD) mechanisms are exceptionally diverse and show high evolutionary rates in fish. Pleuronectiformes is an emblematic fish group characterized by its adaptation to demersal life and its compact genomes. Here, we present a chromosome-level genome assembly of Senegalese sole, a promising European aquaculture species. We combined long- and short-read sequencing and a highly dense genetic map to obtain a contiguous assembly of 613 Mb (N50 = 29.0 Mb, 99% of the assembly in the n = 21 chromosomes of its karyotype). The correspondence between this new assembly and the Senegalese sole chromosomes was established by fluorescence in situ hybridization with BAC probes. Orthology within Pleuronectiformes was assessed by using the chromosome-level genomes of six important commercial flatfishes covering a broad phylogenetic spectrum of the order. A total of 7936 single-gene orthologues, shared by the six species, were used to identify syntenies in Pleuronectiformes and to explore chromosome evolutionary patterns in the order. Whole genome resequencing of six males and six females enabled the identification of 41 fixed allelic variants in the follicle stimulating hormone receptor (fshr) gene, homozygous in females and heterozygous in males, consistent with an XX / XY chromosome system. The observed association between fshr SNPs and sex was confirmed at the species level in a broad sample, which allowed tuning up a molecular sexing tool. Fshr demonstrated differential gene expression between male and female gonads since 86 days post-fertilization, when the gonad was still an undifferentiated primordium, concomitant with the activation of other testis and ovary marker genes, such as amh and cyp19a1a genes, respectively. Interestingly, the Y-linked fshr allele, which included 24 non-synonymous variants, expressed to a higher level than the X-linked allele at all stages. We hypothesize a molecular mechanism hampering the action of the follicle stimulating hormone that would drive the undifferentiated gonad toward testis.

genomics↗

bioRxiv2021

Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes.

An early event in lung oncogenesis is loss of the tumour suppressor gene LIMD1 (LIM domains containing 1); this encodes a scaffold protein, which suppresses tumourigenesis via a number of different mechanisms. Approximately 45% of non-small cell lung cancers (NSCLC) are deficient in LIMD11, yet this subtype of NSCLC has been overlooked in preclinical and clinical investigations. Defining therapeutic targets in these LIMD1 loss-of-function patients is difficult due to a lack of druggable targets, thus alternative approaches are required. To this end, we performed the first drug repurposing screen to identify compounds that confer synthetic lethality with LIMD1 loss in NSCLC cells. PF-477736 was shown to selectively target LIMD1 deficient cells in vitro through inhibition of multiple kinases, inducing cell death via apoptosis. Furthermore, PF-477736 was effective in treating LIMD1-/- tumors in subcutaneous xenograft models, with no significant effect in LIMD1+/+ cells. We have identified a novel drug tool with significant preclinical characterization that serves as an excellent candidate to explore and define LIMD1-deficient cancers as a new therapeutic subgroup of critical unmet need. Significance StatementHere we provide the first proof-of-concept data validating the scope for development of a targeted therapy against the non-small cell lung cancers (NSCLC) subtypes deficient in expression of the LIMD1 tumor suppressor gene. Approximately 45% of NSCLC are deficient in LIMD11 representing at least 1.2 million lung cancer patients worldwide; yet this subtype has been ignored in preclinical and clinical investigations with no targeted therapies available. This seminal study applied synthetic lethality drug screening to target the loss/reduction of LIMD1 in lung cancer and normal cell lines, identifying and validating the multi-kinase inhibitor PF-477736 as a selectively cytotoxic compound towards LIMD1 deficient cells. This study provides rationale for further investigation into targeting LIMD1 loss in lung cancer, thereby addressing a critical unmet need for therapeutic approached to targeting LIMD1-deficent cancer subtypes.

cancer biology↗

bioRxiv2020

Biotic and abiotic factors shaping the genome of cockle (Cerastoderma edule) in the Northeast Atlantic: a baseline for sustainable management of its wild resources

Knowledge on how environmental factors shape the genome of marine species is crucial for sustainable management of fisheries and wild populations. The edible cockle (Cerastoderma edule) is a marine bivalve distributed along the Northeast Atlantic coast of Europe and is an important resource from both commercial and ecological perspectives. We performed a population genomics screening using 2b-RAD genotyping on 9,309 SNPs localised in the cockles genome on a sample of 536 specimens pertaining to 14 beds in the Northeast Atlantic to ascertain its genetic structure regarding environmental variation. Larval dispersal modelling considering species behaviour and interannual variability in ocean conditions was carried out, as an essential background to compare genetic information with. Cockle populations in the Northeast Atlantic were shown to be panmictic and displayed low but significant geographical differentiation across populations (FST = 0.0240; P < 0.001), albeit not across generations. We identified 441 outlier SNPs related to divergent selection, sea surface temperature being the main environmental driver following a latitudinal axis. Two main genetic groups were identified, northwards and southwards of French Brittany, in accordance with our modelling, which demonstrated a barrier for larval dispersal linked to the Ushant front. Further genetic subdivision was observed using outlier loci and considering larval behaviour. The northern group was divided into the Irish/Celtic Seas and the English Channel/North Sea, while the southern group was divided into three subgroups. This information represents the baseline for management of cockles, designing conservation strategies, founding broodstock for depleted beds, and producing suitable seed for aquaculture production.

genomics↗