Publications

Abstract

Comparative neurobiology allows us to investigate relationships between phylogeny and the brain and understand the evolution of traits. Bats constitute an attractive group of mammalian species for comparative studies, given their large diversity in behavioural phenotypes, brain morphology, and array of specialised traits. Currently, the order Chiroptera contains over 1,450 species within 21 families and spans ca. 65 million years of evolution. To date, 194 Neotropical bat species (ca. 13% of the total number of species around the world) have been recorded in Central America. This study includes qualitative and quantitative macromorphological descriptions of the brains of 12 species from six families of Neotropical bats. These analyses, which include histological neuronal staining of two species from different families (Phyllostomus hastatus and Saccopteryx bilineata), show substantial diversity in brain macromorphology including brain shape and size, exposure of mesencephalic regions, and cortical and cerebellar fissure depth. Brain macromorphology can in part be explained by phylogeny as species within the same family are more similar to each other. However, macromorphology cannot be explained by evolutionary time alone as brain differences between some phyllostomid bats are larger than between species from the family Emballonuridae despite being of comparable diverging distances in the phylogenetic tree. This suggests that faster evolutionary changes in brain morphology occurred in phyllostomids — although a larger number of species needs to be studied to confirm this. Our results show the rich diversity in brain morphology that bats provide for comparative and evolutionary studies.

Abstract

We present a reference genome assembly from an individual male Rhynchonycteris naso (Chordata; Mammalia; Chiroptera; Emballonuridae). The genome sequence is 2.46 Gb in span. The majority of the assembly is scaffolded into 22 chromosomal pseudomolecules, with the Y sex chromosome assembled.

Abstract

We describe here the first characterization of the genome of the bat Pteronotus mexicanus, an endemic species of Mexico, as part of the Mexican Bat Genome Project which focuses on the characterization and assembly of the genomes of endemic bats in Mexico. The genome was assembled from a liver tissue sample of an adult male from Jalisco, Mexico provided by the Texas Tech University Museum tissue collection. The assembled genome size was 1.9 Gb. The assembly of the genome was fitted in a framework of 110,533 scaffolds and 1,659,535 contigs. The ecological importance of bats such as P. mexicanus, and their diverse ecological roles, underscores the value of having complete genomes in addressing information gaps and facing challenges regarding their function in ecosystems and their conservation.

Abstract

Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction.

Abstract

Disorders of speech and language are highly heritable, providing strong
support for a genetic basis. However, the underlying genetic architecture is complex,
involving multiple risk factors. This chapter begins by discussing genetic loci associated
with common multifactorial language-related impairments and goes on to
detail the only gene (known as FOXP2) to be directly implicated in a rare monogenic
speech and language disorder. Although FOXP2 was initially uncovered in
humans, model systems have been invaluable in progressing our understanding of
the function of this gene and its associated pathways in language-related areas of the
brain. Research in species from mouse to songbird has revealed effects of this gene
on relevant behaviours including acquisition of motor skills and learned vocalisations
and demonstrated a role for Foxp2 in neuronal connectivity and signalling,
particularly in the striatum. Animal models have also facilitated the identification of
wider neurogenetic networks thought to be involved in language development and
disorder and allowed the investigation of new candidate genes for disorders involving
language, such as CNTNAP2 and FOXP1. Ongoing work in animal models promises
to yield new insights into the genetic and neural mechanisms underlying human
speech and language

Abstract

BACKGROUND: Rare mutations affecting the FOXP2 transcription factor cause a monogenic speech and language disorder. We hypothesized that neural pathways downstream of FOXP2 influence more common phenotypes, such as specific language impairment. METHODS: We performed genomic screening for regions bound by FOXP2 using chromatin immunoprecipitation, which led us to focus on one particular gene that was a strong candidate for involvement in language impairments. We then tested for associations between single-nucleotide polymorphisms (SNPs) in this gene and language deficits in a well-characterized set of 184 families affected with specific language impairment. RESULTS: We found that FOXP2 binds to and dramatically down-regulates CNTNAP2, a gene that encodes a neurexin and is expressed in the developing human cortex. On analyzing CNTNAP2 polymorphisms in children with typical specific language impairment, we detected significant quantitative associations with nonsense-word repetition, a heritable behavioral marker of this disorder (peak association, P=5.0x10(-5) at SNP rs17236239). Intriguingly, this region coincides with one associated with language delays in children with autism. CONCLUSIONS: The FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language.