Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes

Abstract

The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200–300 million years1–3. Due to genetic decay, the human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes’ genes4,5. This evolutionary decay was driven by a series of five “stratification” events. Each event suppressed X-Y crossing over within a chromosome segment or “stratum”, incorporated that segment into the MSY, and subjected its genes to the erosive forces that attend the absence of crossing over2,6. The last of these events occurred 30 million years ago (mya), or 5 million years before the human and Old World monkey (OWM) lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome7–10, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the OWM lineage. To explore this question, we sequenced the MSY of the rhesus macaque, an OWM, and compared it to the human MSY. We discovered that, during the last 25 million years, MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. Within the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 mya. Likewise, the rhesus MSY has not lost any older genes (from strata 1–4) during the past 25 million years, despite major structural differences from the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.

Reconstructing complex regions of genomes using long-read sequencing technology

“…Regions targeted by our approach are frequently missing or grossly misassembled by whole-genome shotgun sequence assembly using either capillary or next-generation sequencing platforms (Alkan et al 2011b), still requiring highquality sequencing of large-insert clones to correctly resolve. Analysis of the mouse and human genomes suggests that these typically correspond to 300-500 regions (;140-150 Mbp) per genome, including in some cases almost entire chromosomes, such as the Y chromosome (Hughes et al 2012). The approach we have described provides a strategy to resolve these more structurally complex regions during the final stages of assembly, ensuring that the 1000-2000 genes mapping therein become incorporated within future mammalian genome assemblies (Alkan et al 2011b;Church et al 2011).…”

“…Finishing of the human and mouse genomes involved selecting large-insert BAC clones and subjecting them to capillary-based shotgun sequence and assembly (English et al 2012). Sanger-based assembly of large-insert clones has been typically a time-consuming and expensive operation requiring the infrastructure of large genome sequencing centers and specialists focused on particular problematic or repetitive regions (Zody et al 2008;Dennis et al 2012;Hughes et al 2012). Such activities can significantly improve the quality of genomes, including the discovery of missing genes and gene families.…”

Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes

“…From studies of mammals (6,7,11,56,57) and Drosophila (58-60), it is known that the Y chromosomes in both groups have lost most of their ancestral gene repertoires and have acquired copious amounts of repetitive and ampliconic/palindromic DNA. In the ∼250 My since Drosophila and Anopheles last shared a common Dipteran ancestor, there has been parallel evolution of heteromorphic sex chromosomes from the same ancestral linkage group (61), implying that the Anopheles Y must have undergone a similar fate of massive ancestral gene loss and genomic degradation.…”

Dynamic Mutation–Selection Balance as an Evolutionary Attractor

“…For example, recently showed that even very small laboratory populations of phage with high mutation rates tend toward fitness plateaus. In addition, a recent comparison of human, chimpanzee, and rhesus Y chromosomes demonstrated that after an initial period of degradation following the halt of recombination, gene loss in the human Y chromosome effectively stopped (Hughes et al 2012). Finally, theoretical work by Loewe (2006) has revealed several "genomic decay paradoxes" (i.e., species that persist despite predicted unsustainable genomic decay), including human mitochondria.…”