Biology subjects

Said, I.

Publications and source records attributed to Said, I..

5 recordsLinked to original sources

bioRxiv2023

The structure of simple satellite variation in the human genome and its correlation with centromere ancestry

Although repetitive DNA forms much of the human genome, its study is challenging due to limitations in assembly and alignment of repetitive short-reads. We have deployed k-Seek, software that detects tandem repeats embedded in single reads, on 2,504 human genomes from the 1,000 Genomes Project to quantify the variation and abundance of simple satellites (repeat units < 20 bp). We find that homopolymers and the Human Satellite 3 monomer make up the largest portions of simple satellite content in humans (mean of [~]19 Mb combined). We discovered[~]50,000 rare tandem repeats that are not detected in the T2T-CHM13v2.0 assembly, including undescribed variants of telomeric- and centromeric repeats. We find broad homogeneity of the most abundant repeats across populations, except for AG-rich repeats that are more abundant in African individuals. We also find cliques of highly similar AG- and AT-rich satellites that are interspersed and form higher-order structures that covary in copy number across individuals, likely through concerted amplification via unequal exchange. Finally, we use centromere-linked polymorphisms to estimate centromeric genetic relatedness between individuals and find a strong predictive relationship between centromeric lineages and centromeric simple satellite abundances. In particular, Human Satellite 2 and Human Satellite 3 abundances correlate with clusters of centromeric ancestry on chromosome 16 and chromosome 9, with some clusters structured by population. These results provide new descriptions of the population dynamics that underlie the evolution of simple satellites in humans.

genomics↗

bioRxiv2022

Sex-linked gene traffic underlies the acquisition of sexually dimorphic UV color vision in Heliconius butterflies

Butterflies have photoreceptor cells that are sensitive to the ultraviolet part of the spectrum due to ultraviolet-sensitive rhodopsin (UVRh), a gene that has been duplicated in the Heliconius genus. In individuals expressing UVRh1 and UVRh2, electrophysiological and behavioral studies demonstrate that these opsin proteins enable discrimination of UV wavelengths. This behavioral trait varies between species, being absent in H. melpomene and limited to females in H. erato. To identify the evolutionary origins of this trait, we first examined UV color vision in H. charithonia, a species related to H. erato in the sara/sapho group. We found that this species also has sexually dimorphic UV color vision. To identify the genetic basis of this trait, we built a reference-grade genome assembly of H. charithonia. We discovered that one duplicate, UVRh1, is present on the W chromosome, making it obligately female-specific. We employed gDNA PCR assays of UVRh1 across the Heliconius genus. In species with sexually dimorphic UVRh1 mRNA expression, UVRh1 gDNA is absent in males, whereas in species with sexually monomorphic UVRh1 mRNA expression, UVRh1 gDNA is found in both sexes. The presence or absence of male UVRh1 expression across the Heliconius phylogeny supports a model where sexual dimorphism was acquired early via movement of a gene duplication to the W-chromosome. We used CRISPR-Cas9 to engineer a deletion in the UVRh1 locus in female H. charithonia and use immunohistochemistry to show that UVRh1 protein expression is absent in mutant tissue, similar to that of males. Our results show that a rare behavioral phenotype, sex-specific UV color vision, was acquired via sex chromosome gene traffic of a duplicated UV rhodopsin.

evolutionary biology↗

bioRxiv2021

Inferred Clades of Transposable Elements in Drosophila Suggest Co-evolution with piRNAs

Transposable elements (TEs) are self-replicating "genetic parasites" ubiquitous to eukaryotic genomes. In addition to conflict between TEs and their host genomes, TEs of the same family are in competition with each other. They compete for the same genomic niches while experiencing the same regime of copy-number selection. This suggests that competition among TEs may favor the emergence of new variants that can outcompete their ancestral forms. To investigate the sequence evolution of TEs, we developed a method to infer clades: collections of TEs that share SNP variants and represent distinct TE family lineages. We applied this method to a panel of 85 Drosophila melanogaster genomes and found that the genetic variation of several TE families shows significant population structure that arises from the population- specific expansions of single clades. We used population genetic theory to classify these clades into younger versus older clades and found that younger clades are associated with a greater abundance of sense and antisense piRNAs per copy than older ones. Further, we find that the abundance of younger, but not older clades, is positively correlated with antisense piRNA production, suggesting a general pattern where hosts preferentially produce antisense piRNAs from recently active TE variants. Together these findings suggest a pattern whereby new TE variants arise by mutation and then increase in copy number, followed by the host producing antisense piRNAs that may be used to silence these emerging variants.

genetics↗

bioRxiv2020

Multiple stages of evolutionary change in anthrax toxin receptor expression in humans

The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a zoonotic disease influenced human evolution, we studied changes in human expression of anthrax toxin receptor 2 (ANTXR2), which encodes a cell surface protein necessary for Bacillus anthracis virulence toxins to cause anthrax disease. In immune cells, ANTXR2 was 8-fold down-regulated in all available human samples compared to non-human primates, indicating regulatory changes early in the evolution of modern humans. We also observed multiple genetic signatures consistent with recent positive selection driving a European-specific decrease in ANTXR2 expression in several non-immune tissues affected by anthrax toxins. Our observations fit a model in which humans adapted to anthrax disease following early ecological changes associated with hunting and scavenging, as well as a second period of adaptation after the rise of modern agriculture.

genetics↗

bioRxiv2019

Fine-mapping complex inversion breakpoints and investigating somatic pairing in the Anopheles gambiae species complex using proximity-ligation sequencing

Chromosomal inversions are fundamental drivers of genome evolution. In the main afro-tropical malaria vector species, belonging to the Anopheles gambiae species complex, inversions play an important role in local adaptation and have a rich history of cytological study. Despite the importance and ubiquity of some chromosomal inversions across the species complex, inversion breakpoints are often challenging to map molecularly due to the presence of large repetitive regions. Here, we develop an approach that uses Hi-C sequencing data to molecularly fine-map the breakpoints of inversions 2Rbc and 2Rd in A. coluzzii. We found that inversion breakpoints occur in large repetitive regions, and strikingly among three inversions analyzed, two breakpoints appear to be reused in two separate inversions. Additionally, we use heterozygous individuals to quantitatively investigate somatic pairing disruption in the regions immediately surrounding inversion breakpoints, and we find that pairing disruption is undetectable beyond approximately 250 Kb from the inversion breakpoints.

evolutionary biology↗