Biology subjects

Martino, G. V.

Publications and source records attributed to Martino, G. V..

3 recordsLinked to original sources

bioRxiv2026

Assembly-independent measurement of human Yq12 heterochromatin reveals population-scale variation and Yq12-derived RNA in testis

Despite advances in long-read sequencing and telomere-to-telomere assembly, population-scale analysis of large satellite arrays remains challenging. Human Yq12 is a megabase-scale heterochromatic region composed primarily of DYZ1/HSat3A6 and DYZ2/HSat1B repeats, whose near-equal proportions are maintained despite extensive variation in total array length. Here, using complete Y-chromosome assemblies, we developed k-mer-based tools to estimate Yq12 size directly from short- and long-read sequencing data without requiring sample-specific complete assemblies. Across 1,597 males from the 1000 Genomes Project, Yq12 length ranged from ~1 to 52 Mb (mean 26.5 Mb) and varied substantially within and between Y haplogroups. Phylogenetic analyses supported long-term constraint of total Yq12 length near an equilibrium of 26 Mb and strongly coupled evolution of DYZ1 and DYZ2 around near-parity composition. In 303 father-son pairs, fathers had longer estimated Yq12 regions in 70.6% of pairs, while sons more often showed DYZ1:DYZ2 ratios closer to 1:1. Testis Iso-Seq identified transcripts containing DYZ1 and DYZ2 satellite sequences, while single-cell RNA-seq revealed their expression in haploid spermatids. These results establish a scalable framework for studying Yq12 population variation, intergenerational dynamics, and transcription, providing new opportunities to investigate how extreme satellite-array variation relates to Y-chromosome evolution and male germ-cell biology.

genetics↗

bioRxiv2026

Population-scale Y chromosome assemblies reveal recurrent remodeling within constrained architectures

The human Y chromosome is among the most structurally dynamic chromosomes in the human genome, yet much of its diversity remains unresolved because of extensive palindromes, ampliconic gene families, satellite-rich heterochromatin and large segmental duplications. What remained unclear was how these diverse forms of variation fit together across the full chromosome, how often similar structures recur in different lineages, and which aspects of organization remain constrained despite rapid sequence turnover. Here, we generated and analyzed 142 nearly complete human Y chromosome assemblies from 17 major haplogroups spanning approximately 180,000 years of evolution, creating a population-scale resource for studying Y chromosome biology and diversity. These assemblies show that structural change on the Y chromosome is recurrent but constrained, even in its most repetitive regions. In the fertility-associated azoospermia factor c (AZFc) region, recurrent inversions, deletions, and complex rearrangements generate a limited repertoire of structural haplotypes. Multicopy ampliconic gene families follow distinct evolutionary paths: DAZ paralogues differ in structural constraint, RBMY evolves within a modular array, and TSPY copy number varies mainly through local expansion and contraction. The centromere and Yq12 heterochromatin vary greatly in size but retain a stable higher-order organization, including a single hypomethylated centromeric core and conserved Yq12 repeat composition and orientation. Methylation across palindromic and ampliconic regions is likewise structured by repeat class, copy order and local architecture. Together, these results provide a population-scale resource for the human Y chromosome and show that its rapid structural evolution is repeatedly funneled into a limited set of architectural outcomes.

genomics↗

bioRxiv2024

Complex genetic variation in nearly complete human genomes

Diverse sets of complete human genomes are required to construct a pangenome reference and to understand the extent of complex structural variation. Here, we sequence 65 diverse human genomes and build 130 haplotype-resolved assemblies (130 Mbp median continuity), closing 92% of all previous assembly gaps1,2 and reaching telomere-to-telomere (T2T) status for 39% of the chromosomes. We highlight complete sequence continuity of complex loci, including the major histocompatibility complex (MHC), SMN1/SMN2, NBPF8, and AMY1/AMY2, and fully resolve 1,852 complex structural variants (SVs). In addition, we completely assemble and validate 1,246 human centromeres. We find up to 30-fold variation in -satellite high-order repeat (HOR) array length and characterize the pattern of mobile element insertions into -satellite HOR arrays. While most centromeres predict a single site of kinetochore attachment, epigenetic analysis suggests the presence of two hypomethylated regions for 7% of centromeres. Combining our data with the draft pangenome reference1 significantly enhances genotyping accuracy from short-read data, enabling whole-genome inference3 to a median quality value (QV) of 45. Using this approach, 26,115 SVs per sample are detected, substantially increasing the number of SVs now amenable to downstream disease association studies.

genomics↗