Lineage-Specific Expansions of Retroviral Insertions within the Genomes of African Great Apes but Not Humans and Orangutans
Chris T Yohn 2005 PLoS Biol.3: e110

RV.infections of the germ-line have the potential to episodically alter gene-function & genome-structure during the course of evolution.
Horizontal transmissions between spp have been proposed,
but little evidence exists for such events in the human/gr.ape lineage of evolution.

Based on analysis of finished BAC chimp genome sequence, we characterize a RV.element: Pan troglodytes endogenous retrovirus-1 PTERV1,
- it has become integrated in the germ-line of African great ape & Old World monkey spp,
- but is absent from humans & Asian ape genomes.
We unambiguously map 287 RV integration sites:
c 95.8 % of the insertions occur at non-orthologous regions between closely related spp.
Phylogenetic analysis of the endogenous RV reveals:
- the Gorilla & Pan elements share a monophyletic origin with a subset of the OWM RV elements,
- but the average sequence divergence exceeds neutral expectation for a strictly nuclear inherited DNA molecule.
Within Pan, there is a significant integration bias against genes:
only 14 of these insertions map within intronic regions.
6 out of 10 of these genes (for which there are expression data) show significant differences in transcript expression between Hs & Pan.
Our data are cons.x a RV infection that bombarded the genomes of Pan & Gorilla, independently & concurrently, 3–4 Ma.
We speculate on the potential impact of such recent events on the evolution of Hs & gr.apes.

.... Discussion

Most human endogenous RVs are thought to have emerged as a result of ancient infections >25 Ma, followed by subsequent retrotransposition events.
Several lines of evidence indicate:
Pan & Gorilla PTERV1 copies arose from an exogenous source:
1) there is <4 % between the location of insertions among Pan, Gorilla, Macaca & Papio:
unlikely endogenous copies existed in a common ancestor, and then became subsequently deleted in the Homo lineage & Pongo lineage.
2) the PTERV1 phylogenetic tree is incons.x the generally accepted spp tree for primates,
this suggests a horizontal transmission (vs a vertical transmission from a common ape ancestor).
An alternative explanation, proposed by some anthropologists: is the primate phylogeny is grossly incorrect?
This seems unlikely in light of the extensive molecular evolutionary data that have been collected over the last few years:
these clearly place orang as the outgroup species to the HPG-clade, and OXMs as an outgroup to the human/ape lineage.
3) the single nucleotide substitution rate for the viruses is significantly greater than what would be expected for neutral nuclear DNA, e.g.
the extent of Pan & Gorilla substitution has been estimated at c 0.016 ± 0.008 substitutions/site (+-half of this variation occurred in each lineage),
the endogenous RV sequence that we examined showed significantly greater divergence (0.038 ± 0.003) (62 pairwise comparisons),
a similar excess of divergence was observed if only intra-specific RV divergence was compared (0.028 & 0.041 ± 0.003 for Pan & Gorilla resp.) ,
such an acceleration of neutral substitution would easily be explained if it were composed of a viral & nuclear component.
4) if we partition synonymous & non-synonymous substitution sites, we observe a deficiency of amino-acid AA replacement sites (K a/K s = 0.63),
we observed a similar result (K a/K s = 0.44) for one of the ambiguous overlap loci shared between Gorilla & Pan,
this significant departure from neutrality would be an expected residuum if a portion of PTERV1 sequence variation accrued while being propagated as an infectious virus:
f it were solely derived from an ancestral endogenous element, a neutral pattern (vs a relaxed pattern of purifying selection) would be expected.
5) in the few examples where the insertion sites have been mapped precisely, both the length & the composition of the target site duplications are characteristic of the patterns of RV integrations.

These multiple lines of indirect data indicate: PTERV1 likely emerged from an exogenous source,
but its source reservoir (if it still exists) is unknown.
PTERV1 does not share high sequence identity to any known RV.
Translation of the protein-encoding portions shows sequence similarity (c 50 %) to feline leukemia viruses, murine leukemia viruses & the baboon endogenous RV.
Such sequences are known to transfer frequently between the soma of spp, and occasionally enter the germline.
Interestingly, 1 of the 3 main branches of OWM PTERV1 may actually share a monophyletic origin with the Gorilla & Pan elements.
One possible scenario: was this RV introduced into the gr.ape lineages by horizontal transmission? from contact with an ancient OWM species?

Our data support a model where ancestral Pan & Gorilla spp were infected independently & contemporaneously by an exogenous source of gamma-RV 3–4 Ma.
Similar infections with a related RV appear common-place among the OWMs,
but contemporary human & orang populations show no molecular vestiges of this infection.
The molecular basis for this historical difference is unclear.
Geographic isolation of Miocene African & Asian ape lineages might account for part of this difference,
but the ancestral habitat of early hominids is generally thought to have overlapped, in part, with the African apes.
Both Asian (macaque) & African (baboon) OWMs show evidence of PTERV1 proviral integrations <2 Ma:
the exogenous source virus is either endemic to both continents, or ancestral populations frequented both continents.

Several speculative scenarios may explain the RV absence in both the orang & human lineages:

Did the Afr.apes evolve a susceptibility? did humans & Asian apes develop resistance to infection?
but in either scenario, convergent evolution would have had to have occurred with respect to the viral infections.
Studies of the RV infection of the Lake Casitas mouse population reveal:
such susceptibility/resistance genes may emerge very quickly among closely related strains of mice.

Another scenario: did the lineage that ultimately gave rise to Hs not occupy the same habitat as the ancestral Pan & Gorilla lineages?
An excursion by early hominids to Eurasia during the time that PTERV1 infected African gr.apes, and then a return to Africa would explain this phylogenetic inconsistency.
Also possible: this effect may have been created by dramatic differences in ancestral population structure, e.g.
if the human & orang ancestral populations were substantially larger than those of the Afr.gr.apes, the fixation of new insertions (1/2N) would occur much more rapidly within small inbred populations, even if similar infection rates existed.
A similar model has recently been proposed (albeit in the opposite direction) to explain an increase of “apparent” Alu Ya5 & Yb8 retro-position activity in the human lineage, but not in Pan & Gorillas:
interestingly, documented differences in the patterns of endogenous RV between domesticated & feral spp have been attributed to inbreeding,
but there is no evidence to date that the ancestral populations of chimps were smaller than that of humans.
In fact, recent studies suggest: ancestral Pan populations may have been 2 to 4x largerthan the effective human population size (>10,000).
A dramatic population crash in ancestral Gorilla & Pan populations would be required to explain the effect we have observed.
Further population genetic studies of contemporary gr.apes or PA work may help to eliminate these & other possible scenarios.

Not unreasonably, these ancient infections reduced effective population size if fitness of ancestral populations were compromised by the infection.
Recently, such an ancient RV infection was predicted to have occurred in Pan, based on a completely separate line of reasoning:
De Groot cs reported a dramatic reduction of genetic variability of intronic sequence from the major histo-compatibility complex MHC-I human leukocyte antigen loci (A, B, C) among Pan when compared to human populations.
This is a notable exception to other studies that demonstrate 2- to 4-fold greater diversity in chimp populations than in humans.
Based on the evol.age of some of the new lineages & comparisons between chimp & bonobo, De Groot cs estimated the loss of MHC-I diversity to have occurred before subspeciation 2–3 Ma.
Due to the central role that pathogens play in eliciting immune response against viral infections, and the fact that high-frequency MHC-I haplotypes target conserved epitopes of the HIV-1 virus, the authors speculated:
are the unusual pattern of MHC-I diversity the result of a pandemic RV infection that positively selected a small nr of lineages to be swept through the population?
Our findings are cons.x the timing of this loss of diversity, and may represent the genomic vestiges of this RV pandemic.

Due to its integration into the germ-line, this RV infection may have had a double impact.
-- At a genetic level, at least 5 % of the RV insertions would have resulted in lethality when homozygosed,
the 3-fold integration bias against gene insertions may represent a strong signature of this selection,
this distribution is in sharp contrast to patterns of somatic RV infection & recent class-II human endogenous RV elements that map near or within genes.
In a background of reduced survival & lowered fecundity, genetic bottlenecks may have been frequent occurrences among ancestral Pan & Gorilla populations after speciation.
During this time of RV crisis, small subsets of RV-induced mutations may have been fixed at an increased frequency.
The mutation & fixation of multiple weakly deleterious mutations could, in theory, promote further saltatory & irrevocable changes in phenotypic traits among these progenitor populations.
Such episodic mutational events may have simultaneously propelled spp differentiation, and cemented reproductive barriers between humans & the African gr.apes.
In such a scenario, greater sequence divergence over these regions might be expected because of a lack of introgression upon secondary contact among incipient spp.
It will be interesting to compare patterns of divergence for these sites with those for other genomic regions in humans & African great apes when genome sequence of sufficient quality becomes available.

Op vrijdag 21 april 2023 om 13:55:34 UTC+2 schreef littor...@gmail.com:
> Lineage-Specific Expansions of Retroviral Insertions within the Genomes of African Great Apes but Not Humans and Orangutans
> Chris T Yohn 2005 PLoS Biol.3: e110

Sorry for having sent this twice... (becoming a bit older??)