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

The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200–300 million years[superscript 1, 2, 3]. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes’ genes owing to genetic decay[superscript 4, 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 over[superscript 2, 6]. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome[superscript 7, 8, 9, 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 Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, 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. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1–4) during the past 25 million years, despite its major structural differences to 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

Gene duplication and fragmentation in the zebra finch major histocompatibility complex

BACKGROUND: Due to its high polymorphism and importance for disease resistance, the major histocompatibility complex (MHC) has been an important focus of many vertebrate genome projects. Avian MHC organization is of particular interest because the chicken Gallus gallus, the avian species with the best characterized MHC, possesses a highly streamlined minimal essential MHC, which is linked to resistance against specific pathogens. It remains unclear the extent to which this organization describes the situation in other birds and whether it represents a derived or ancestral condition. The sequencing of the zebra finch Taeniopygia guttata genome, in combination with targeted bacterial artificial chromosome (BAC) sequencing, has allowed us to characterize an MHC from a highly divergent and diverse avian lineage, the passerines. RESULTS: The zebra finch MHC exhibits a complex structure and history involving gene duplication and fragmentation. The zebra finch MHC includes multiple Class I and Class II genes, some of which appear to be pseudogenes, and spans a much more extensive genomic region than the chicken MHC, as evidenced by the presence of MHC genes on each of seven BACs spanning 739 kb. Cytogenetic (FISH) evidence and the genome assembly itself place core MHC genes on as many as four chromosomes with TAP and Class I genes mapping to different chromosomes. MHC Class II regions are further characterized by high endogenous retroviral content. Lastly, we find strong evidence of selection acting on sites within passerine MHC Class I and Class II genes. CONCLUSION: The zebra finch MHC differs markedly from that of the chicken, the only other bird species with a complete genome sequence. The apparent lack of synteny between TAP and the expressed MHC Class I locus is in fact reminiscent of a pattern seen in some mammalian lineages and may represent convergent evolution. Our analyses of the zebra finch MHC suggest a complex history involving chromosomal fission, gene duplication and translocation in the history of the MHC in birds, and highlight striking differences in MHC structure and organization among avian lineages

Acute Splenic Infarct in Beta-Thalassemia Minor: A Novel Combination of Heterozygous Beta-Globin Mutations With Latent Phenotypes and the Clinical Implications

Defects in hemoglobin (Hb) involve qualitative as well as quantitative alterations in globin physiology. The former include classic sickle cell disease, while the latter include the thalassemias. Individuals with alpha- and beta-thalassemia (alpha- and beta-thal) \u27trait\u27 have reduced Hb chain synthesis. These individuals are asymptomatic, their condition often coming to light as incidental findings. We report here the evaluation of a previously healthy man with beta-thal minor who presented with acute splenic infarct in the context of severe dehydration. A hypercoagulability evaluation was performed and found to be negative. Hemoglobin electrophoresis was conducted to confirm the patient\u27s thalassemia minor state. Sequencing of genomic DNA revealed the presence of distinct beta-globin gene mutations. We postulate that in this previously asymptomatic individual, his dual heterozygous mutation status in conjunction with severe environmental stressors altered his \u27benign\u27 Hb physiology and resulted in an acute arterial thrombosis, suggesting a sub classification of beta-thal minor into silent and latent categories

Polymorphism in the promoter region of the tumor necrosis factor-alpha gene in cattle herds naturally infected and uninfected with the Bovine Leukemia Virus

The objective of this study was to describe and compare the genetic structure (TNF-α-position 824) of dairy cattle herds infected and not infected with the bovine leukemia virus (BLV). The results of the present study indicate that BLV-positive herds were characterized by similar genetic structure (TNF-α-824A/G). The genetic equilibrium in these herds was preserved, but a tendency to increased frequency of G/G homozygotes was found. The genetic structure of the healthy herd differed considerably from that of leukemic herds

Distribution of issues addressed and an example region.

<p>(Top Panel) Issues for GRCh37, GRCh37.p1, and GRCh37.p2, broken down by type. Issue types are: Clone Problem: The issue is contained within a single clone. This may be a single nucleotide difference or a clone mis-assembly. Path Problem: There is evidence that the tiling path within a given region is incorrect and we will need to update the path. GRC Housekeeping: Changes use to help regularize the tiling path. Missing Sequence: Sequence that we can’t yet place on the assembly. Mapping studies are ongoing to help place these sequences. Variation: There is evidence to suggest that complex variation is complicating a region and an alternate allele may need to be produced. Gap: The issue concerns filling a gap. Unknown: Issue is still under investigation for classification. (Bottom Panel) Details for issue HG-2, a Path Problem. The representation in NCBI36 was a mixed haplotype. The tiling paths for NCBI36 and GRCh37 are shown. Blue clones are anchor clones that are in NCBI36, the GRCh37 chr4 path, and the GRCh37 alternate locus path. Red clones represent the UGT2B17 insertion path and dark gray clones represent the UGT2B17 deletion path. The light gray clone was not used in NCBI36, but was used in GRCh37 to complete the alternate locus.</p